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Abstract Conjugative plasmids promote the dissemination and evolution of antimicrobial resistance in bacterial pathogens. However, plasmid acquisition can produce physiological alterations in the bacterial host, leading to potential fitness costs that determine the clinical success of bacteria-plasmid associations. In this study, we use a transcriptomic approach to characterize the interactions between a globally disseminated carbapenem resistance plasmid, pOXA-48, and a diverse collection of multidrug resistant (MDR) enterobacteria. Although pOXA-48 produces mostly strain-specific transcriptional alterations, it also leads to the common overexpression of a small chromosomal operon present in Klebsiella spp. and Citrobacter freundii strains. This operon includes two genes coding for a pirin and an isochorismatase family proteins (pfp and ifp), and shows evidence of horizontal mobilization across Proteobacteria species. Combining genetic engineering, transcriptomics, and CRISPRi gene silencing, we show that a pOXA-48-encoded LysR regulator is responsible for the plasmid-chromosome crosstalk. Crucially, the operon overexpression produces a fitness benefit in a pOXA-48-carrying MDR K. pneumoniae strain, suggesting that this crosstalk promotes the dissemination of carbapenem resistance in clinical settings.

During the last decade, soundscape research has become one of the most active topics in Acoustics. This work provides a nonlinear variable selection analysis over the well-known dataset ‘emo-soundscapes’. Namely, we provide a selection of the soundscape indicators using a nonlinear and nonparametric model as a regression tree method. Modern techniques (proposed in the literature) have been used, first for ranking the variables and then for choosing the effective number of features. We have also compared and discussed our results with those provided previously in the literature. This study, based on modern techniques in selecting the effective number of variables, confirms the result presented in previous recent work (but based on a linear model) that very parsimonious models should be considered (in the case of a nonlinear model, it is based on very few variables, from 2 to 4, depending on the output). All the results are obtained by analyzing a single dataset. As future research works, we plan to extend our study by also considering alternative datasets.

In this study, a parameter identification approach for the fractional-order piezoelectric creep model is proposed. Indeed, creep is a wide-impacting phenomenon leading to time-dependent deformation in spite of constant persistent input. The creep behavior results in performance debasement, especially in applications with low-frequency responses. Fractional-Order (FO) modeling for creep dynamics has been proposed in recent years, which has demonstrated improved modeling precision compared to integer-order models. Still, parameter uncertainty in creep models is a challenge for real-time control. Aiming at a faster identification process, the proposed approach in this paper identifies the model parameters in two layers, i.e., one layer for the fractional-order exponent, corresponding to creep, and the other for the integer-order polynomial coefficients, corresponding to mechanical resonance. The proposed identification strategy is validated by utilizing experimental data from a piezoelectric actuator used in a nanopositioner and a piezoelectric sensor.

IntroductionLactate is an important signaling molecule with autocrine, paracrine and endocrine properties involved in multiple biological processes including regulation of gene expression and metabolism. Levels of lactate are increased chronically in diseases associated with cardiometabolic disease such as heart failure, type 2 diabetes, and cancer. Using neonatal ventricular myocytes, we tested the hypothesis that chronic lactate exposure could decrease the activity of cardiac mitochondria that could lead to metabolic inflexibility in the heart and other tissues.MethodsNeonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 5, 10, or 20 mM lactate and CPT I and II activities were tested using radiolabelled assays. The molecular species profile of the major mitochondrial phospholipid, cardiolipin, was determined using electrospray ionization mass spectrometry along with reactive oxygen species (ROS) levels measured by Amplex Red and mitochondrial oxygen consumption using the Seahorse analyzer.ResultsCPT I activity trended downward (p = 0.07) and CPT II activity significantly decreased with lactate exposure (p < 0.001). Cardiolipin molecular species containing four 18 carbon chains (72 carbons total) increased with lactate exposure, but species of other sizes decreased significantly. Furthermore, ROS production was strongly enhanced with lactate (p < 0.001) and mitochondrial ATP production and maximal respiration were both significantly down regulated with lactate exposure (p < 0.05 and p < 0.01 respectively).ConclusionsChronic lactate exposure in cardiomyocytes leads to a decrease in fatty acid transport, alterations of cardiolipin remodeling, increases in ROS production and decreases in mitochondrial oxygen consumption that could have implications for both metabolic health and flexibility. The possibility that both intra-, or extracellular lactate levels play roles in cardiometabolic disease, heart failure, and other forms of metabolic inflexibility needs to be assessed in vivo.

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 μg/dL (confirmed ACS if >5 μg/dL and possible ACS if 1.8–5 μg/dL) in the absence of spe cific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was simil ar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patien ts with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-thi rd of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar.

PurposeTo compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA).MethodsA systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group).ResultsA total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels.ConclusionIn addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.

The main contribution of this work is the proposal and hardware implementation of an algorithm for the time synchronization of orthogonal frequency division multiplexing (OFDM) modulation with Hermitian symmetry for visible light communications (VLC) systems, using only the real component of the transmitted signal. OFDM systems with Hermitian Symmetry are able to satisfy the high data rates demanded by many VLC systems, as well as deal with inter-symbol interference (ISI). However, these systems are characterized by being very vulnerable to synchronization problems in both time and frequency. Time synchronization being the most critical. In this paper, a novel time synchronization technique for OFDM systems with Hermitian Symmetry is proposed. This technique is based on the inclusion of a post-FFT synchronization stage to achieve time synchronization with one-sample precision. For this purpose, the relationship that exists between an offset in the frequency domain with an offset in the time domain is used, and with this information the correction of the frequency offset from the time domain is performed. An original and novel algorithm has been designed and implemented in hardware, which uses the cyclic prefix (CP) elimination stage to perform the time correction. The performance validation of the proposed technique is done with the implementation, using the ZYBO $^{{^{\mathrm{ TM}}}}$ development board, of a complete OFDM system applied to a real VLC system.

Orthogonal frequency-division multiplexing (OFDM) systems have been widely implemented in guided and non-guided communications. Even though they are becoming a standard for popular technologies such as WiFi, their implementation in newly emerging ones is still in evolution. As the number of connected devices increases, the radio frequency (RF) channel gets crowded. Here is where visible light communication (VLC) links gain interest. VLC offers a wireless alternative to RF with a trade-off between the necessity of line of sight with the offer of a free, highly secure, and immune to electromagnetic interference communication channel. This paper proposes a programmable software implementation of an OFDM system using a novel phase correction technique for VLC channels. The new equation considers two types of phase shifts, one that will be non-deterministic (has a random variation) and another that will be deterministic and, therefore, can be estimated and corrected. This second can be split into two: one that comes from the clock differences and has more impact on higher subcarriers, and the second that appears from the electronics of the link and will directly impact the symbols' phase. The main difference with current phase correction techniques is the identification and estimation of the deterministic noise specific to VLC systems. The deterministic noise impact all subcarriers equally and must be subtracted before the measure of the shift induced by the differences between the transmitter and receiver clocks. Another difference is that the analysis and tests have been done with data collected in an actual hardware implementation.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = −0.362, p < 0.001) and total coronary calcification (r = −0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (β = −0.189; −0.739–−0.027; p = 0.035) and high-sensitivity troponin I (β = −0.301; −0.259–−0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525–0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

Abstract Streptococcus pneumoniae colonizes the human nasopharynx, a multi-species microbial niche. Pneumococcal Ami-AliA/AliB oligopeptide permease is an ABC transporter involved in environmental sensing with peptides AKTIKITQTR, FNEMQPIVDRQ, and AIQSEKARKHN identified as ligands of its substrate binding proteins AmiA, AliA, and AliB, respectively. These sequences match ribosomal proteins of multiple bacterial species, including Klebsiella pneumoniae. By mass spectrometry, we identified such peptides in the Klebsiella pneumoniae secretome. AmiA and AliA peptide ligands suppressed pneumococcal growth, but the effect was dependent on peptide length. Growth was suppressed for diverse pneumococci, including antibiotic-resistant strains, but not other bacterial species tested, with the exception of Streptococcus pseudopneumoniae, whose growth was suppressed by the AmiA peptide ligand. By multiple sequence alignments and protein and peptide binding site predictions, for AmiA we have identified the location of an amino acid in the putative binding site whose mutation appears to result in loss of response to the peptide. Our results indicate that pneumococci sense the presence of Klebsiella pneumoniae peptides in the environment.

Hemoglobin-based oxygen carriers (HBOCs) offer a promising alternative to conventional blood transfusions in emergency scenarios. However, achieving optimal stability, functionality, and biocompatibility in HBOCs remains a significant challenge. In this study, we employed a HBOC formulation consisting of hemoglobin (Hb) encapsulated within zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs). These NPs were subsequently coated with metal phenolic networks (MPNs) and polyethylene glycol (PEG) to impart antioxidant properties and enhance their stability and biocompatibility. Hb-loaded ZIF-8 NPs were synthesized using a rapid, environmentally friendly protocol and exhibited desirable properties, including an average size of approximately 150 nm, a negative surface charge (zeta potential of −14 mV), high encapsulation efficiency (approximately 65%), and substantial drug loading capacity (around 70%). The MPN coating significantly enhanced stability across various buffers and cell media and endowed the NPs with antioxidant properties. Meanwhile, the PEG layer conferred stealth properties, potentially extending circulation times in vivo. Furthermore, the NPs showed excellent biocompatibility in terms of cell viability and hemolysis rate studies. They also efficiently bound and released oxygen across multiple cycles, demonstrating preserved functionality. These attributes highlight the potential of our novel HBOC as an effective oxygen delivery system and position our formulation as a promising candidate for clinical application in critical care, providing a strategic alternative to traditional blood transfusions. [ABSTRACT FROM AUTHOR]

Objective: To compare the presentation and evolution of primary aldosteronism (PA) in the elderly (≥65 years) and young patients (

Abstract Background Pancreatic cancer is one of the leading causes of cancer mortality and one of the most lethal malignant neoplasms worldwide. It is known for its local tumor extension to the liver; other common sites include the lung, distant lymph nodes, and bone. Brain metastases are extremely rare and represent less than 0.6% of all brain metastases. Case report We report the case of a 66-year-old Caucasian female known to have adenocarcinoma of the tail of the pancreas treated with chemotherapy. During follow-up, thoracoabdominal computed tomography scans did not reveal any residual tumor or any metastasis. Moreover, tumor markers were within normal limits. She presented to the emergency department of our institution following an episode of a generalized tonic–clonic seizure 5 years following the initial diagnosis. Brain magnetic resonance imaging revealed an expansive left frontal intraaxial lesion compatible with high-grade glioma. The patient underwent surgical treatment. Histological examination revealed pancreatic metastasis. Conclusions Thought to be rare, metachronous cerebral pancreatic metastasis should be kept in mind in patients with pancreatic cancer. Early diagnosis and complete surgical resection play a key role in the survival of these patients.