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Introduction: In post-COVID survivors, transforming growth factor-beta-1 (TGF-ß1) might mediate fibroblast activation, resulting in persistent fibrosis. Methods: In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-ß1 was measured in blood and exhaled breath condensate (EBC). Results: At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-ß1. Plasma TGF-ß1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-ß receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-ß1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. Discussion: TGF-ß1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

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BACKGROUND: Open liver resection necessitates a substantial upper abdominal inverted-L incision, resulting in severe pain and compromising patient recovery. Despite the efficacy of epidural analgesia in providing adequate postoperative analgesia, the potential epidural-related adverse effects should be carefully considered. This study aims to compare the efficacy and safety of continuous epidural analgesia and intravenous analgesia in open liver resection. METHODS: A retrospective study was conducted, collecting data from patients who underwent open liver resection between 2007 and 2017. Propensity score matching was implemented to mitigate confounding variables, with patients being matched in a 1:1 ratio based on propensity scores. The primary outcome was the comparison of postoperative morphine consumption at 24, 48, and 72 hours between the two groups. Secondary outcomes included pain scores, postoperative outcomes, and epidural-related adverse effects. RESULTS: A total of 612 patients were included, and after matching, there were 204 patients in each group. Opioid consumption at 24, 48, and 72 hours postoperatively was statistically lower in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). However, there was no significant difference in pain scores (p = 0.422). Additionally, perioperative hypotension requiring treatment, as well as nausea and vomiting, were significantly higher in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). CONCLUSIONS: Epidural analgesia is superior to intravenous morphine in terms of reducing postoperative opioid consumption within the initial 72 h after open liver resection. Nevertheless, perioperative hypotension, which necessitates management, should be approached with consideration and vigilance. TRIAL REGISTRATION: The study was registered in the Clinical Trials Registry at www. CLINICALTRIALS: gov/ , NCT number: NCT06301932.

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Background: The endovascular approach has emerged as standard therapy for many intracranial aneurysms (IAs) to prevent hemorrhage, yet its long-term durability varies considerably. The aim of this study was to evaluate the safety and effectiveness of an initially deliberate endovascular approach regarding IA hemorrhage rates over a long-term follow-up period. Methods: This retrospective single-center study included all consecutive patients with endovascularly treated IAs who presented between January 2008 and December 2020 with a follow-up of at least 12 months. The primary endpoint was the proportion of patients with long-term IA hemorrhage rates and reperfusion. The secondary endpoint was treatment-related morbidity and mortality. Independent risk factors for IA reperfusion over the long term were analyzed using multivariate logistic regression. Results: Endovascular treatment was the therapy of choice for 333 patients with IAs, among whom 188 (57%) experienced rupture upon presentation. Complete coiling (Raymond I) was noted in 162 (49%) of the patients, with primary supportive devices being used in 51 (15%) patients. After a median (±SD) follow-up time of 34 ± 41 months (range 12-265 months), IA reperfusion was noted in 158 (47%), necessitating retreatment in 105 (32%) of the patients. Over the long term, hemorrhage was noted in four (1%) patients. Multivariate analysis revealed aneurysmal multilobarity (HR 1.8, 95%CI 1.2-2.7; p = 0.004) and a patient age of ≥50 years (HR 1.7, 95% CI 1.1-2.5, p = 0.01) as independent predictors of reperfusion over time. Intervention-related morbidity was noted in 16 (4.8%) patients, namely, thrombosis formation and contrast extravasation in 8 (2.4%) patients each, while no intervention-induced mortality was observed. Conclusion: In the long term, the hemorrhage rate in patients with IA with an initially more conservative endovascular approach is low. Therefore, a deliberate endovascular treatment approach might be justified.

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Paenibacillus larvae is the causative agent of American Foulbrood (AFB), the most severe bacterial disease affecting honey bee (Apis mellifera) larvae. It was first reported in Uruguay in 1999. Here, we summarize the monitoring strategy carried out from 2001 to date, based on nationwide surveys sampling honey from colonies (2001/2002, 2011, 2021) or from honey storage tanks (2014-2019). We also discuss the actions carried out for the prevention of AFB outbreaks. Uruguay's experience in managing AFB for nearly 25 years without antibiotic use, might provide some helpful ideas for other countries working on AFB control programs.

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BACKGROUND: Pneumonias are events of great prognostic significance in COPD, so it is important to identify predictive factors. OBJECTIVE: To determine whether poor glycemic control is related to an increased risk of pneumonia in COPD. METHOD: A historical cohort study conducted in a COPD clinic. The first severe exacerbation after the first visit was analyzed. Exacerbations that presented with pulmonary infiltrates were identified. A Cox proportional hazards analysis was performed including the values of glycosylated hemoglobin (Hb1Ac) in patients with diabetes mellitus (DM) and variables that could plausibly be related to the risk of pneumonia. The best Hb1Ac value to predict pneumonia was assessed using receiver-operating characteristics analysis. RESULTS: There were 1124 cases included in the study. A total of 411 patients were admitted to the hospital at least once and 87 were diagnosed with pneumonia. Variables associated with the risk of pneumonia were previous admissions due to COPD and Hb1Ac values (HR: 2.33, 95% CI: 1.06 - 5.08, p = 0.03). A higher body mass index (BMI) was associated with a lower risk of pneumonia. The optimal cutoff point for Hb1Ac to predict pneumonia risk was 7.8 %. The patients were classified into 3 groups: (1) no DM, (2) controlled DM (Hb1AC < 7.8 %), (3) uncontrolled DM (Hb1AC ≥ 7.8 %). The risk of pneumonia for group 2 was not different from group 1, while the risk for group 3 was significantly higher than for groups 1 and 2 (HR: 4.52, 95 % CI: 1.57 - 13.02). CONCLUSIONS: Poor control of DM is a predictor of the risk of pneumonia in COPD. The cutoff point of 7.8 % for this variable seems to be the most useful to identify patients at risk.

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INTRODUCTION: Avoiding patient-prosthesis mismatch (PPM) in patients with small aortic annulus (SAA) during aortic valve replacement (AVR) is still a challenging surgical problem. Among surgical options available, aortic root enlargement (ARE) and stentless valve implantation (SVI) are the two most commonly used strategies. This systematic review will be conducted searching for superiority evidence based on comparative studies between these two options. METHODS AND ANALYSIS: This systematic review will include all relevant articles published from 1 January 1946 to 31 March 2024, with available full texts from Medline (Ovid), Embase, Cochrane Library and Web of Science databases, without any language restriction. Observational studies and randomised controlled trials comparing surgical results of ARE versus SVI for AVR in patients with small aortic root will be screened. Studies will be classified into three groups: group 1 for studies that reported SVI or other tissue valve outcomes without comparing them with ARE outcomes; group 2 for studies that reported ARE outcomes without comparing them with SVI outcomes; and group 3 for studies that compared ARE outcomes with SVI outcomes. The quality of the evidence of each study will be evaluated according to Oxford Centre for Evidence-Based Medicine criteria. ETHICS AND DISSEMINATION: Ethical approval is not required because no primary data are collected. The findings will be presented at scientific conferences and/or reported in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: PROSPERO, CRD42023383793.

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The basidiomycete fungus Leucoagaricus gongylophorus is able to grow in the fungus garden of leaf-cutter ants. This mutualistic interaction has driven the evolutionary adaptation of L. gongylophorus, shaping its metabolism to produce enzymes adept at lignocellulosic biomass degradation. In this study, we undertook the comprehensive sequencing, assembly, and functional annotation of the genome of L. gongylophorus strain LEU18496, mutualistic fungus of the Atta mexicana. Our genomic analyses revealed a distinctive bimodal nature to the genome: a predominant region characterized by AT enrichment and low genetic density, alongside a smaller region exhibiting higher GC content and higher genetic density. The presence of transposable elements (TEs) within the AT-enriched region suggests genomic compartmentalization, facilitating differential evolutionary rates. With a gene count of 6748, the assembled genome of L. gongylophorus LEU18496 surpasses previous reports for this fungal species. Inspection of genes associated with central metabolism unveiled a remarkable abundance of carbohydrate-active enzymes (CAZymes) and fungal oxidative lignin enzymes (FOLymes), underscoring their pivotal roles in the life cycle of this fungus.

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BACKGROUND: High-risk Pulmonary Embolism (PE) mortality remains very high. Systemic thrombolysis is effective but carries significant complications and contraindications related to the hemorrhagic risk. Percutaneous thrombectomy using aspiration catheters may be an alternative in patients with a high bleeding risk. OBJECTIVE: This study aimed to evaluate the results of catheter-directed thrombectomy using aspiration dedicated catheters in patients with high-risk PE and absolute contraindication to systemic thrombolysis, with specific focus on procedural success, safety, and in-hospital outcomes. METHODS: A prospective study enrolled all consecutive patients diagnosed with high-risk pulmonary embolism and absolute contraindication to systemic thrombolysis, who underwent percutaneous pulmonary thrombectomy using dedicated aspiration catheters. The study documented the effectiveness and complications of the procedure, as well as patient outcomes at discharge and during the follow-up period. RESULTS: Thirteen patients underwent percutaneous pulmonary thrombectomy using aspiration dedicated catheters. The procedure was successful for all patients, resulting in hemodynamic and respiratory improvement within the first 24 h. No deaths attributable to cardiovascular or respiratory causes occurred during admission or follow-up. Furthermore, no serious adverse events or complications were reported during the procedure or hospitalization. CONCLUSIONS: Percutaneous pulmonary thrombectomy with dedicated aspiration catheters in patients with high-risk pulmonary embolism and contraindications to systemic thrombolysis was associated with excellent clinical results and low rate of complications.

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Poly(3-hydroxybutyrate) (P(3HB)) is an attractive biodegradable plastic alternative to petroleum-based plastic. However, the cost of microbial-based bioplastic production mainly lies in the cultivation medium. In this study, we screened the isolates capable of synthesizing P(3HB) using sugarcane bagasse (SCB) waste as a carbon source from 79 Bacillus isolates that had previously shown P(3HB) production using a commercial medium. The results revealed that isolate S356, identified as Bacillus cereus using 16S rDNA and gyrB gene analysis, had the highest P(3HB) accumulation. The highest P(3HB) yield (5.16 g/L, 85.3% of dry cell weight) was achieved by cultivating B. cereus S356 in an optimal medium with 1.5% total reducing sugar with SCB hydrolysate as the carbon source and 0.25% yeast extract as the nitrogen source. Transmission electron microscopy analysis showed the accumulation of approximately 3-5 P(3HB) granules in each B. cereus S356 cell. Proton nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy analyses confirmed that the polymer extracted from B. cereus S356 was P(3HB). Notably, during cultivation for P(3HB) plastic production, B. cereus S356 also secreted bacteriocin, which had high antibacterial activity against the same species (Bacillus cereus). Overall, this work demonstrated the possibility of co-producing eco-friendly biodegradable plastic P(3HB) and bacteriocin from renewable resources using the potential of B. cereus S356.

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BACKGROUND: The aim of this study was to compare the predictive performance of three statistical models-logistic regression, classification tree, and structural equation model (SEM)-in predicting severe dengue illness. METHODS/FINDINGS: We adopted modified classification of dengue illness severity based on WHO 1997 guideline. Predictive models were constructed using demographic factors and laboratory indicators on the day of fever occurrence. We developed statistical predictive models using data from two hospital cohorts in Thailand, consisting of 257 Thai children. Different predictive models for each category of severe dengue illness were developed employing logistic regression, classification tree, and SEM. The probability of discrimination of each model for severe output of disease was analyzed with external validation data sets from 55 and 700 patients not used in model development. From external validation using predictors on the day of presentation to the hospital, the area under the receiver operating characteristic curve was between 0.65 and 0.84 for the regression model. It was between 0.73 and 0.85 for SEM models. Classification tree models showed good results of sensitivity, ranging from 0.95 to 0.99. However, they showed poor specificity ranging from 0.10 to 0.44. CONCLUSIONS: Our study showed that SEM is comparable to logistic regression or classification tree, which was widely used for more severe form of dengue prediction.

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PURPOSE: The routine use of intraoperative digital subtraction angiography (iDSA) increases detection of intracranial aneurysm (IA) remnants after microsurgical clipping. Spontaneous thrombosis of IA remnants after clipping is considered a rare phenomenon. We analyse iDSA characteristics to find predictors for IA remnant thrombosis. METHODS: IA with intraoperative detection of a remnant after clipping were identified and divided into remnants experiencing spontaneous thrombosis, and remnants with long-term patency and/or remnant growth. Angiographic features of iDSA were analysed and compared between the two groups. RESULTS: Of 37 IAs with intraoperative remnant on 3D-iDSA, five sustained a spontaneous remnant thrombosis and remained occluded in long-term follow-up. In all five cases, iDSA revealed delayed inflow and consequent stasis of the contrast agent until the late venous phase. On the other hand, in all cases with persistent long-term IA remnants (n = 32) iDSA demonstrated timely arterial contrast inflow and wash-out without stasis of intra-aneurysmal contrast agent. CONCLUSIONS: Contrast stasis in IA remnants during iDSA appears to predict long-term IA occlusion, indicating that clip correction manoeuvres or even attempted endovascular treatment of the remnant IA may be avoided in these patients.

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BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

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The Asp-tRNAAsn/Glu-tRNAGln amidotransferase (GatCAB) has been proposed as a novel antibacterial drug target due to its indispensability in prominent human pathogens. While several inhibitors with in vitro activity have been identified, none have been demonstrated to have potent activity against live bacteria. In this work, seven non-hydrolyzable transition state mimics of GatCAB were synthesized and tested as the transamidase inhibitors against GatCAB from the human pathogen Helicobacter pylori. Notably, the methyl sulfone analog of glutamyl-adenosine significantly reduced GatCAB's transamination rate. Additionally, four lipid-conjugates of these mimics displayed antibacterial activity against Bacillus subtilis, likely due to enhanced cell permeability. Inhibitory activity against GatCAB in live bacteria was confirmed using a sensitive gain-of-function dual luciferase reporter in Mycobacterium bovis-BCG. Only the lipid-conjugated methyl sulfone analog exhibited a significant increase in mistranslation rate, highlighting its cell permeability and inhibitory potential. This study provides insights for developing urgently needed novel antibacterial agents amidst emerging antimicrobial drug resistance.

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BACKGROUND: Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). METHODS: We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. RESULTS: Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-ß (IFN-ß) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-ß proteins, has the capacity to alter endothelial function. CONCLUSIONS: Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.

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Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

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