"Cap polyposis", refractory to drug treatment, including infliximab.

Cap polyposis is a rare disease characterized by the presence of inflammatory polyps with an adherent fibrin sheath ("cap"), in variable number and size, in the rectum and sigmoid. It presents with tenesmus, mucous stools and rectorrhagia. There is currently no standardized treatment, having been treated empirically with aminosalicylates, oral or rectal steroids, metronidazole, H. pylori eradication therapy and infliximab with variable results. In refractory cases, endoscopic resection of polyps may be used and surgery may even be necessary. We present the case of a 36-year-old patient diagnosed in our center with cap polyposis, refractory to both pharmacological and endoscopic treatment, and therefore treatment with infliximab was decided out of indication. The case we present is the fourth case of cap polyposis treated with infliximab available in the current literature and highlights the difficulty of achieving a clinical response with pharmacological treatment, including biologic drugs such as infliximab.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

"Analysis of Macular Pigment Optical Density in Childhood: A Systematic Review".

PURPOSE: This systematic review studies the relationship between Macular Pigment Optical Density (MPOD) values and cognitive and visual function in childhood. METHODS: It included cross-sectional, observational studies or controlled clinical trials in humans between 0 and 18 years of age, analyzing MPOD values in 3 main databases: PubMed, Scopus and Web of Science. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. RESULTS: Thirteen studies were included in this systematic review. The relationship of cognitive function, visual function and diverse variables with MPOD was analyzed in 4, 4 and 5 studies, respectively. The age of the participants ranged between premature infants to 12 years. Most of the studies used Heterochromatic Flicker Photometry (HFP) with macular densitometer to obtain MPOD values. MPOD values ranged between 0 (undetectable) to 0.66 ± 0.03 d.u. Only 4 articles studied the relationship between MPOD values and dietary intake of lutein and zeaxanthin using questionnaires about diet. CONCLUSIONS: Lutein and zeaxanthin accumulation plays an important role during the maturational stage and childhood development. Although cognitive function is more strongly correlated with MPOD values, the relationship with visual function remains unclear, and further studies are required to support this relationship.

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.

BACKGROUND: Long-term consequences of COVID-19 are still partly known. AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up.

Vaccination and Nutritional Outcomes of Hemodialysis Patients Infected With SARS-CoV-2.

BACKGROUND: Patients on hemodialysis are particularly vulnerable to COVID-19 and may have a reduced response to vaccination because of a decreased immune response. The nutritional status before or during the infection could also impact on the clinical effectiveness of vaccination. OBJECTIVES: We aim to describe the evolution of clinical and nutritional biomarkers of hemodialysis patients infected with SARS-CoV-2 and to assess their association with vaccination status. METHODS: An observational, analytic, longitudinal, retrospective multicenter study was carried out in 82 patients on hemodialysis with SARS-CoV-2 infection. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), anthropometry, and biochemical parameters. The association of the vaccine doses with clinical- and nutritional-related variables was also evaluated. RESULTS: The percentage of vaccinated patients was similar to that of nonvaccinated patients. Before infection, most of the patients were malnourished. They presented lower albumin, creatinine, and urea levels than the well-nourished patients. Significant deterioration of nutritional status after infection was evidenced considering GNRI score, dry weight, and body mass index. Albumin and creatinine also decreased significantly after infection, whereas C-reactive protein increased in the acute phase. Significant inverse correlation was found between the variation of post-pre GNRI scores and basal albumin and C-reactive protein at 7 days. In addition, we observed the opposite trend between albumin at 30 days and basal cholesterol. A negative value in the GNRI variation was associated with bilateral pneumonia, need for hospitalization, and nutritional support. Vaccinated patients presented substantially less bilateral pneumonia and hospitalization. No significant effects were observed between vaccine doses and the variation in nutritional status, although a positive correlation was detected with the albumin at 7 days and C-reactive protein before infection and the number of vaccine doses received. DISCUSSION: COVID-19 is associated with affectations in the nutritional status and biomarkers in hemodialysis patients. In this study, vaccines have shown a protective effect against the clinical consequences of COVID. However, they have shown limitations in preventing the deterioration of nutritional status after infection. The results highlight the importance of promoting the vaccination in these patients as well as incorporating nutritional assessment before, during, and after the infection.

Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in P. aeruginosa, including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in P. aeruginosa is a promising strategy to fight this clinically relevant pathogen.

The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa.

Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σECF) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σECF-associated anti-σ factor, and the function of the Prc and RseP proteases. In this work, we have identified another protease that modulates CSS activity, namely the periplasmic carboxyl-terminal processing protease CtpA. CtpA functions upstream of Prc in the proteolytic cascade and seems to prevent the Prc-mediated proteolysis of the CSS anti-σ factor. Importantly, using zebrafish embryos and the A549 lung epithelial cell line as hosts, we show that mutants in the rseP and ctpA proteases of the human pathogen Pseudomonas aeruginosa are considerably attenuated in virulence while the prc mutation increases virulence likely by enhancing the production of membrane vesicles.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry.

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM.

Air- and water-stable and photocatalytically active germanium-based 2D perovskites by organic spacer engineering.

There is increasing interest in the role of metal halide perovskites for heterogeneous catalysis. Here, we report a Ge-based 2D perovskite material that shows intrinsic water stability realized through organic cation engineering. Incorporating 4-phenylbenzilammonium (PhBz) we demonstrate, by means of extended experimental and computational results, that PhBz2GeBr4 and PhBz2GeI4 can achieve relevant air and water stability. The creation of composites embedding graphitic carbon nitride (g-C3N4) allows a proof of concept for light-induced hydrogen evolution in an aqueous environment by 2D Ge-based perovskites thanks to the effective charge transfer at the heterojunction between the two semiconductors.

Accommodative disorders in non-presbyopic subjects with type 1 diabetes without retinopathy: A comparative, cross-sectional study.

PURPOSE: The purpose of this study was to assess accommodative function in non-presbyopic individuals diagnosed with type 1 diabetes (T1D) without any signs of retinopathy, to determine the existence of possible accommodative disorders related to this disease, and to determine the influence of T1D duration and glycosylated haemoglobin values on accommodative function. METHODS: This comparative, cross-sectional study included 60 participants between 11 and 39 years old, 30 with T1D and 30 controls, with no previous eye surgery, ocular disease or medication that could affect the results of the visual examination. Amplitude of accommodation (AA), negative and positive relative accommodation (NRA and PRA), accommodative response (AR) and accommodative facility (AF) were assessed using the tests that showed the highest repeatability. Participants were classified based on normative values into 'insufficiency, excess or normal results', and a diagnosis of accommodative disorders (accommodative insufficiency, accommodative infacility and accommodative excess) was made. RESULTS: Participants with T1D had statistically significant lower AA and AF and higher NRA values than the controls. Furthermore, AA was significantly and inversely correlated with age and the duration of diabetes; however, AF and NRA were only correlated with disease duration. In the classification by accommodative variables, a higher percentage of 'insufficiency values' was observed in the T1D group (50%) than in the control group (6%; p < 0.001). In terms of accommodative disorders, accommodative infacility was the most prevalent (15%), followed by accommodative insufficiency (10%). CONCLUSIONS: Our findings indicate that T1D affects most accommodative parameters, with accommodative insufficiency being associated with this disease.

Contrast sensitivity function under three light conditions in patients with type 1 diabetes mellitus without retinopathy: a cross-sectional, case-control study.

PURPOSE: To determine whether patients with type 1 diabetes mellitus (T1DM), without any sign of diabetic retinopathy, have any alteration in Contrast Sensitivity Function (CSF), in relation to patients without this disease, and whether CSF assessment in three different light conditions can be an effective test in the early detection of diabetic retinopathy. METHODS: A prospective, cross-sectional, case-control study was preformed including 80 patients (40 with T1DM without diabetic retinopathy and 40 controls) between 11 and 47 years old. CSF was assessed at four spatial frequencies (3, 6, 12 and 18 cycles/degree) using the CSV-1000E test, under three light conditions: high (550 lx), medium (200 lx) and low (< 2 lx). RESULTS: A lower CSF in the T1DM group was found at the three light conditions studied. The most spatial frequency affected was 18 cpd, 0.08 log units (p = 0.048) in high, 0.10 log units (p = 0.010) in medium (p = 0.010) and 0.16 log units (p < 0.001) in low-light conditions in mean CS values. The least spatial frequency affected was 3 cpd (p > 0.05 in all three light conditions). CONCLUSION: Patients with T1DM, without diabetic retinopathy, presented a loss of CS to sine-wave gratings, with respect to people with the same characteristics without the disease, mainly at medium and high frequencies, and in medium and low-light conditions.

Evaluation of Celligent® Biomimetic Water Gradient Contact Lens Effects on Ocular Surface and Subjective Symptoms.

This study aimed to evaluate the non-invasive and subjective symptoms associated with Lehfilcon A water gradient silicone hydrogel contact lenses with bacterial and lipid resistance technology. A prospective, longitudinal, single-centre, self-controlled study was conducted among silicone hydrogel contact lens wearers. Non-invasive analysis of the pre-lens tear film was performed using the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA), and the meibomian glands were evaluated with the Cobra® HD infrared meibographer. After 30 days of contact lens wear, the subjects were re-evaluated to determine the changes in conjunctival redness, subjective dry eye disease, tear meniscus height, lipid pattern, and non-invasive break-up time. Results showed that the lipid layer thickness decreased significantly from 2.05 ± 1.53 to 0.92 ± 1.09 Guillon patterns, and the tear meniscus height decreased from 0.21 ± 0.04 to 0.14 ± 0.03. The mean pre-lens non-invasive break-up time (NIBUT) significantly increased from 15.19 ± 9.54 to 25.31 ± 15.81 s. The standard Patient Evaluation of Eye Disease (SPEED) score also decreased from 7.39 ± 4.39 to 5.53 ± 4.83. The results suggest that Lehfilcon A significantly reduced lipid and aqueous tear film volume but improved break-up time and subjective dry eye symptoms.

Mechanisms of iron homeostasis in Pseudomonas aeruginosa and emerging therapeutics directed to disrupt this vital process.

Pseudomonas aeruginosa is an opportunistic pathogen able to infect any human tissue. One of the reasons for its high adaptability and colonization of host tissues is its capacity of maintaining iron homeostasis through a wide array of iron acquisition and removal mechanisms. Due to their ability to cause life-threatening acute and chronic infections, especially among cystic fibrosis and immunocompromised patients, and their propensity to acquire resistance to many antibiotics, the World Health Organization (WHO) has encouraged the scientific community to find new strategies to eradicate this pathogen. Several recent strategies to battle P. aeruginosa focus on targeting iron homeostasis mechanisms, turning its greatest advantage into an exploitable weak point. In this review, we discuss the different mechanisms used by P. aeruginosa to maintain iron homeostasis and the strategies being developed to fight this pathogen by blocking these mechanisms. Among others, the use of iron chelators and mimics, as well as disruption of siderophore production and uptake, have shown promising results in reducing viability and/or virulence of this pathogen. The so-called 'Trojan-horse' strategy taking advantage of the siderophore uptake systems is emerging as an efficient method to improve delivery of antibiotics into the bacterial cells. Moreover, siderophore transporters are considered promising targets for the developing of P. aeruginosa vaccines.

Impact of genetic structural variants in factor XI deficiency: identification, accurate characterization, and inferred mechanism by long-read sequencing.

BACKGROUND: Congenital factor XI (FXI) deficiency is a probably underestimated coagulopathy that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single-nucleotide variants and small insertion/deletions because they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVES: To identify and characterize the SVs affecting F11. METHODS: The study was performed in 93 unrelated subjects with FXI deficiency recruited in Spanish hospitals over a period of 25 years (1997-2022). F11 was analyzed by next-generation sequencing, multiplex ligand probe amplification, and long-read sequencing. RESULTS: Our study identified 30 different genetic variants. Interestingly, we found 3 SVs, all heterozygous: a complex duplication affecting exons 8 and 9, a tandem duplication of exon 14, and a large deletion affecting the whole gene. Nucleotide resolution obtained by long-read sequencing revealed Alu repetitive elements involved in all breakpoints. The large deletion was probably generated de novo in the paternal allele during gametogenesis, and despite affecting 30 additional genes, no syndromic features were described. CONCLUSION: SVs may account for a high proportion of F11 genetic defects implicated in the molecular pathology of congenital FXI deficiency. These SVs, likely caused by a nonallelic homologous recombination involving repetitive elements, are heterogeneous in both type and length and may be de novo. These data support the inclusion of methods to detect SVs in this disorder, with long-read-based methods being the most appropriate because they detect all SVs and achieve adequate nucleotide resolution.

Tear Film Dynamics between Low and High Contact Lens Dry Eye Disease Questionnaire (CLDEQ-8) Score with a Lehfilcon A Silicone Hydrogel Water Gradient Contact Lens: A Non-Invasive Methodology Approach.

The purpose of this study is to evaluate the tear film dynamics between individuals with low and high Contact Lens Dry Eye Disease Questionnaire (CLDEQ-8) scores when wearing Lehfilcon A silicone hydrogel water gradient contact lenses. In this study, we implemented a longitudinal, single-location, self-comparison investigation. Variables measured included conjunctival redness, lipid layer thickness, tear meniscus height, first and mean non-invasive break-up time, CLDEQ-8, and standard patient evaluation of eye dryness (SPEED). In the second phase, participants were re-evaluated after 30 days of wearing the contact lenses to assess the tear film wearing the lenses. In a longitudinal comparison by group, we found that lipid layer thickness decreased 1.52 ± 1.38 (p < 0.01) and 0.70 ± 1.30 (p = 0.01) Guillon patterns degrees in the low and high CLDEQ-8 group, respectively. MNIBUT increased in 11.93 ± 17.93 (p < 0.01) and 7.06 ± 12.07 (p < 0.01) seconds. Finally, LOT increased in 22.19 ± 27.57 (p < 0.01) and 16.87 ± 25.09 (p < 0.01). In conclusion, this study demonstrates the effectiveness of Lehfilcon A silicone hydrogel water gradient contact lenses in improving tear film stability and reducing subjective dry eye symptoms in individuals with low and high CLDEQ-8 scores. However, it also led to an increase in conjunctival redness and a decrease in tear meniscus height.

Usefulness and Limitations of Multiple Ligation-Dependent Probe Amplification in Antithrombin Deficiency.

Multiplex ligation-dependent probe amplification (MLPA) identifies genetic structural variants in SERPINC1 in 5% of cases with antithrombin deficiency (ATD), the most severe congenital thrombophilia. Our aim was to unravel the utility and limitations of MLPA in a large cohort of unrelated patients with ATD (N = 341). MLPA identified 22 structural variants (SVs) causing ATD (6.5%). MLPA did not detect SVs affecting introns (four cases), and the diagnosis was inaccurate in two cases according to long-range PCR or nanopore sequencing. MLPA was used to detect possible hidden SVs in 61 cases with type I deficiency with single nucleotide variations (SNVs) or small insertion/deletion (INDEL). One case had a false deletion of exon 7, as the 29-bp deletion affected an MLPA probe. We evaluated 32 variants affecting MLPA probes: 27 SNVs and 5 small INDELs. In three cases, MLPA gave false-positive results, all diagnosed as deletions of the affected exon: a small INDEL complex, and two SNVs affecting MLPA probes. Our study confirms the utility of MLPA to detect SVs in ATD, but also shows some limitations in detecting intronic SVs. MLPA renders imprecise and false-positive results for genetic defects which affect MLPA probes. Our results encourage the validation of MLPA results.

Transcriptional organization and regulation of the Pseudomonas putida K1 type VI secretion system gene cluster.

The type VI secretion system (T6SS) is an antimicrobial molecular weapon that is widespread in Proteobacteria and offers competitive advantages to T6SS-positive micro-organisms. Three T6SSs have recently been described in Pseudomonas putida KT2440 and it has been shown that one, K1-T6SS, is used to outcompete a wide range of phytopathogens, protecting plants from pathogen infections. Given the relevance of this system as a powerful and innovative mechanism of biological control, it is critical to understand the processes that govern its expression. Here, we experimentally defined two transcriptional units in the K1-T6SS cluster. One encodes the structural components of the system and is transcribed from two adjacent promoters. The other encodes two hypothetical proteins, the tip of the system and the associated adapters, and effectors and cognate immunity proteins, and it is also transcribed from two adjacent promoters. The four identified promoters contain the typical features of σ70-dependent promoters. We have studied the expression of the system under different conditions and in a number of mutants lacking global regulators. P. putida K1-T6SS expression is induced in the stationary phase, but its transcription does not depend on the stationary σ factor RpoS. In fact, the expression of the system is indirectly repressed by RpoS. Furthermore, it is also repressed by RpoN and the transcriptional regulator FleQ, an enhancer-binding protein typically acting in conjunction with RpoN. Importantly, expression of the K1-T6SS gene cluster is positively regulated by the GacS-GacA two-component regulatory system (TCS) and repressed by the RetS sensor kinase, which inhibits this TCS. Our findings identified a complex regulatory network that governs T6SS expression in general and P. putida K1-T6SS in particular, with implications for controlling and manipulating a bacterial agent that is highly relevant in biological control.

Post-COVID-19 Symptoms and Heart Disease: Incidence, Prognostic Factors, Outcomes and Vaccination: Results from a Multi-Center International Prospective Registry (HOPE 2).

BACKGROUND: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. METHODS: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. RESULTS: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81-3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04-0.19). CONCLUSIONS: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Preparation of Heterojunctions Based on Cs3Bi2Br9 Nanocrystals and g-C3N4 Nanosheets for Photocatalytic Hydrogen Evolution.

Heterojunctions based on metal halide perovskites (MHPs) are promising systems for the photocatalytic hydrogen evolution reaction (HER). In this work, we coupled Cs3Bi2Br9 nanocrystals (NCs), obtained by wet ball milling synthesis, with g-C3N4 nanosheets (NSs), produced by thermal oxidation of bulk g-C3N4, in air. These methods are reproducible, inexpensive and easy to scale up. Heterojunctions with different loadings of Cs3Bi2Br9 NCs were fully characterised and tested for the HER. A relevant improvement of H2 production with respect to pristine carbon nitride was achieved at low NCs levels reaching values up to about 4600 µmol g-1 h-1. This work aims to provide insights into the synthesis of inexpensive and high-performing heterojunctions using MHP for photocatalytic applications.