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Pseudomonas aeruginosa is an opportunistic human pathogen causing devastating acute and chronic infections in individuals with compromised immune systems. Its highly notorious persistence in clinical settings is attributed to its ability to form antibiotic-resistant biofilms. Biofilm is an architecture built mostly by autogenic extracellular polymeric substances which function as a scaffold to encase the bacteria together on surfaces, and to protect them from environmental stresses, impedes phagocytosis and thereby conferring the capacity for colonization and long-term persistence. Here we review the current knowledge on P. aeruginosa biofilms, its development stages, and molecular mechanisms of invasion and persistence conferred by biofilms. Explosive cell lysis within bacterial biofilm to produce essential communal materials, and interspecies biofilms of P. aeruginosa and commensal Streptococcus which impedes P. aeruginosa virulence and possibly improves disease conditions will also be discussed. Recent research on diagnostics of P. aeruginosa infections will be investigated. Finally, therapeutic strategies for the treatment of P. aeruginosa biofilms along with their advantages and limitations will be compiled.

This study demonstrates that novel polymer production can be achieved by introducing pTAM, a broad-host-range plasmid expressing codon-optimized genes encoding Clostridium propionicum propionate CoA transferase (PctCp, Pct532) and a modified Pseudomonas sp. MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1Ps6-19, PhaC1400), into phaC mutant strains of the native polymer producers Sinorhizobium meliloti and Pseudomonas putida. Both phenotypic analysis and gas chromatography analysis indicated the synthesis and accumulation of biopolymers in S. meliloti and P. putida strains. Expression in S. meliloti resulted in the production of PLA homopolymer up to 3.2% dried cell weight (DCW). The quaterpolymer P (3HB-co-LA-co-3HHx-co-3HO) was produced by expression in P. putida. The P. putida phaC mutant strain produced this type of polymer the most efficiently with polymer content of 42% DCW when cultured in defined media with the addition of sodium octanoate. This is the first report, to our knowledge, of the production of a range of different biopolymers using the same plasmid-based system in different backgrounds. In addition, it is the first time that the novel polymer (P(3HB-co-LA-co-3HHx-co-3HO)), has been reported being produced in bacteria.

Dengue fever, driven by four serotypes of the Dengue virus and transmitted by Aedes aegypti, presents a major global health threat, impacting billions in tropical and subtropical regions. Severe cases, such as Dengue Shock Syndrome, result in significant mortality, particularly without prompt intervention, placing immense strain on healthcare systems in resource-limited settings. Dengue vaccines—Dengvaxia, Qdenga, and TV003/TV005 (NIH dengue vaccine) —offer potential for control, yet their implementation has been challenged by safety issues, including heightened risks in seronegative individuals, presumably due to antibody-dependent enhancement, though the precise mechanisms remain under investigation. Although newer vaccines show promise in efficacy and safety, their real-world performance across diverse populations remains poorly understood due to insufficient post-marketing surveillance. This commentary evaluates the deficiencies in adverse event reporting, identifying key obstacles such as inconsistent practices, inadequate infrastructure, and weak regulatory frameworks in endemic areas. Drawing on established pharmacovigilance models from the United States and United Kingdom, we propose real-time, transparent reporting systems to strengthen safety monitoring. Recommendations include standardized digital tools, capacity enhancement, and global data-sharing initiatives to ensure interoperability and accessibility. The erosion of public trust following past vaccine controversies highlights the urgent need for transparency to bolster acceptance and inform policy. By integrating advanced surveillance with international cooperation, these measures can refine risk-benefit assessments, rebuild confidence in immunization programs, and maximize the protective impact of dengue vaccines, ultimately reducing the burden on vulnerable populations worldwide.

Background There are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of the gut microbiota by diet could lead to healthier aging. The purpose of this study was to test the effect of diets differing in sugar, fat, and fiber content upon the gut microbiota of mice humanized with microbiota from healthy or frail older people. We also performed a 6-month dietary fiber supplementation in three human cohorts representing three distinct life-stages. Methods Mice were colonized with human microbiota and then underwent an 8-week dietary intervention with either a high-fiber/low-fat diet typical of elderly community dwellers or a low-fiber/high-fat diet typical of long-stay residential care subjects. A cross-over design was used where the diets were switched after 4 weeks to the other diet type to identify responsive taxa and innate immunity changes. In the human intervention, the subjects supplemented their normal diet with a mix of five prebiotics (wheat dextrin, resistant starch, polydextrose, soluble corn fiber, and galactooligo-saccharide) at 10 g/day combined total, for healthy subjects and 20 g/day for frail subjects, or placebo (10 g/day maltodextrin) for 26 weeks. The gut microbiota was profiled and immune responses were assayed by T cell markers in mice, and serum cytokines in humans. Results Humanized mice maintained gut microbiota types reflecting the respective healthy or frail human donor. Changes in abundance of specific taxa occurred with the diet switch. In mice with the community type microbiota, the observed differences reflected compositions previously associated with higher frailty. The dominance of Prevotella present initially in community inoculated mice was replaced by Bacteroides , Alistipes , and Oscillibacter . Frail type microbiota showed a differential effect on innate immune markers in both conventional and germ-free mice, but a moderate number of taxonomic changes occurring upon diet switch with an increase in abundance of Parabacteroides , Blautia , Clostridium cluster IV, and Phascolarctobacterium . In the human intervention, prebiotic supplementation did not drive any global changes in alpha- or beta-diversity, but the abundance of certain bacterial taxa, particularly Ruminococcaceae ( Clostridium cluster IV), Parabacteroides , Phascolarctobacterium , increased, and levels of the chemokine CXCL11 were significantly lower in the frail elderly group, but increased during the wash-out period. Conclusions Switching to a nutritionally poorer diet has a profound effect on the microbiota in mouse models, with changes in the gut microbiota from healthy donors reflecting previously observed differences between elderly frail and non-frail individuals. However, the frailty-associated gut microbiota did not reciprocally switch to a younger healthy-subject like state, and supplementation with prebiotics was associated with fewer detected effects in humans than diet adjustment in animal models.

Bacteria threaten human and animal health, and standard antibiotics no longer effective. Antibiotic-resistant microorganisms can make infection treatment challenging and perhaps fail. Investigating the attributes of cyclotide, a peptide with promising antibacterial properties that holds great potential in the field of antibiotic research. The structure of these cyclic peptides involves six conserved cysteine residues that form three disulfide bonds, resulting in a cyclic cystine knot (CCK). This feature guarantees their durability when exposed to changes in temperature, chemicals, and enzymatic degradation. The two cyclotides, cycloviolacin O17 and mra30, were obtained from Viola dalatensis Gadnep through a series of techniques including the use of a 50% acetonitrile/49% miliQ water/1% formic acid solution for extraction, ammonium salt precipitation, RP-HPLC purification and sequence identification by LC-MS/MS. These cyclotides exhibit antibacterial effects on specific strains of bacteria like Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa at a concentration of 0.2 mg/mL, leading to inhibition zones ranging from 10 to 14 mm. In addition, the disulfide bonds play a crucial role in the antibacterial function of cyclotides. Disrupting the disulfide bonds through ankylation reaction results in the loss of antibacterial properties in the cyclotides (cyO17 and mra30). The minimum inhibitory concentration (MIC) values of mra30 and cyO17 are significantly low, ranging from 0.1 to 0.6 µM. These values are approximately three times lower than the MIC values observed in salt precipitation samples.

In this paper, we address the challenges of inferring and learning from a substantial number of observations (N≫1) with a Gaussian process regression model. First, we propose a flexible construction of well-adapted covariances originally derived from specific differential operators. Second, we prove its convergence and show its low computational cost scaling as O(Nm2) for inference and O(m3) for learning instead of O(N3) for a canonical Gaussian process where N≫m. Moreover, we develop an implementation that requires less memory O(m2) instead of O(N2). Finally, we demonstrate the effectiveness of the proposed method with simulation studies and experiments on real data. In addition, we conduct a comparative study with the aim of situating it in relation to certain cutting-edge methods.

BackgroundAs tumor biology takes precedence over anatomic staging to determine breast cancer (BC) prognosis, there is growing interest in limiting axillary surgery. There is a need for tools to identify patients at the lowest risk of harboring axillary lymph node (ALN) disease, to determine when omission of sentinel lymph node biopsy (SLNB) may be appropriate. We examined whether a nomogram using preoperative axillary ultrasound (axUS) findings, clinical tumor size, receptor status, and grade to calculate the probability of nodal metastasis (PNM) has value in surgical decision making.MethodsThis was a retrospective analysis of female patients (February 2011–October 2014) with invasive BC who underwent preoperative axUS and axillary surgery. Cases with locally advanced BC, neoadjuvant treatment, or bilateral BC were excluded. PNM was calculated for each case. Using various PNM thresholds, the proportion of cases with ALN metastasis on pathology was examined to determine an optimal PNM cut-point to predict ALN negativity.ResultsOf 357 included patients, 72% were node-negative on surgical staging, and 69 (19.6%) had a PNM < 9.3%. Of these 69 patients, 6 had ALN metastasis on surgical pathology, yielding a false negative rate (FNR) of 8.7% for predicting negative ALN when a PNM threshold of < 9.3% was used.ConclusionA nomogram incorporating axUS findings and tumor characteristics identified a sizeable subgroup (19.6%) in whom ALN was predicted to be negative, with an 8.7% FNR. Surgeons can use this nomogram to quantify the probability of ALN metastasis and select patients who may benefit from omitting SLNB.

Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3–2·2] vs 2·2 [1·3–3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo. In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function. Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy. BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health.

Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB—namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)—to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits.