Diabetes mellitus with poor glycemic control is a risk factor for pneumonia in COPD.

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.

Aortic root enlargement versus stentless valve implantation for avoidance of patient-prosthesis mismatch in patients with small aortic root: protocol for a systematic review.

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.

Sequencing, assembly, and genomic annotation of Leucoagaricus gongylophorus LEU18496, a dikarya mutualistic species.

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.

Comparison of predictive models using logistic regression, classification tree, and structural equation model for severe dengue.

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.

Intra-aneurysmal contrast agent stasis during intraoperative digital subtraction angiography may predict long-term occlusion after clipping.

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.

Valorization of Sugarcane Bagasse for Co-Production of Poly(3-hydroxybutyrate) and Bacteriocin Using Bacillus cereus Strain S356.

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.

Percutaneous pulmonary thrombectomy with aspiration catheters in patients with high-risk pulmonary embolism and absolute contraindication to systemic thrombolysis.

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.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

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.

Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange.

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.

A quest for novel antimicrobial targets: Inhibition of Asp-tRNAAsn/Glu-tRNAGln amidotransferase (GatCAB) by synthetic analogs of aminoacyl-adenosine in vitro and live bacteria.

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.

Dynamic digestion of a high protein beverage based on amaranth: Structural changes and antihypertensive activity.

An amaranth beverage (AB) was subjected to a simulated process of dynamic gastrointestinal digestion DIDGI®, a simple two-compartment in vitro dynamic gastrointestinal digestion system. The structural changes caused to the proteins during digestion and the digesta inhibitory capacity of the angiotensin converting enzyme (ACE) were investigated. In gastric compartment the degree of hydrolysis (DH) was 14.7 ± 1.5 % and in the intestinal compartment, proteins were digests in a greater extent (DH = 60.6 ± 8.4 %). Protein aggregation was detected during the gastric phase. The final digesta obtained both at the gastric and intestinal level, showed ACE inhibitory capacity (IC50 80 ± 10 and 140 ± 20 µg/mL, respectively). Purified fractions from these digesta showed even greater inhibitory capacity, being eluted 2 (E2) the most active fraction (IC50 60 ± 10 µg/mL). Twenty-six peptide sequences were identified. Six of them, with potential antihypertensive capacity, belong to A. hypochondriacus, 3 agglutinins and 3 encrypted sequences in the 11S globulin. Results obtained provide new and useful information on peptides released from the digestion of an amaranth based beverage and its ACE bioactivity.

The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

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.

Study protocol to examine the effects of acute exercise on motor learning and brain activity in children with developmental coordination disorder (ExLe-Brain-DCD).

INTRODUCTION: Developmental coordination disorder (DCD) is one of the most prevalent pediatric chronic conditions. Without proper intervention, significant delays in motor skill performance and learning may persist until adulthood. Moderate-to-vigorous physical exercise has been proven to improve motor learning (adaptation and consolidation) in children with or without disorders. However, the effect of a short bout of physical exercise on motor adaptation and consolidation in children with DCD has not been examined. Furthermore, the role of perceptual-motor integration and attention as mediators of learning has not been examined via neuroimaging in this population. OBJECTIVES: Therefore, the primary aims of this project will be to compare children with and without DCD to (a) examine the effect of acute exercise on motor learning (adaptation and consolidation) while performing a rotational visuo-motor adaptation task (rVMA), and (b) explore cortical activation in the dorsolateral- and ventrolateral-prefrontal cortex areas while learning the rVMA task under rest or post-exercise conditions. METHODS: One hundred twenty children will be recruited (60 DCD, 60 controls) and within-cohort randomly assigned to either exercise (13-minute shuttle run task) or rest prior to performing the rVMA task. Adaptation and consolidation will be evaluated via two error variables and three retention tests (1h, 24h and 7 days post adaptation). Cortical activation will be registered via functional near-infrared spectroscopy (fNIRS) during the baseline, adaptation, and consolidation. DISCUSSION: We expect to find exercise benefits on motor learning and attention so that children with DCD profiles will be closer to those of children with typical development. The results of this project will provide further evidence to: (a) better characterize children with DCD for the design of educational materials, and (b) establish acute exercise as a potential intervention to improve motor learning and attention.

Helminth infection in wild boars in Primorye, Russia.

Wild boars have a worldwide distribution and also have major economic, veterinary, and medical importance. Due to a small amount of data on the parasitic fauna of wild boars in the Russian Far East, especially in Prymorye territory, a post-mortem parasitic examination of 20 wild boars was provided. The general prevalence was 25%, and a total of six helminth species, including one larva stage, were found. The most prevalent helminth species were Gnathostoma doloresi (25%) and Metastrongylus elongatus (20%). Followed by Trichuris suis and Ascaris suum (15%). The lowest prevalence was registered for Cysticercus tenuicollis (the larvae stage of T. hydatigena). Parasites were found in each region, with the highest prevalence registered in the Chuguevskii region. Totally 100% of adult boars were positive for helminth infections, instead of 60% of young specimens. Some helminthes found (G. doloresi, T. suis, A. suum) have zoonotic potential and can be involved in the circulation of human parasitic diseases, especially in rural areas. Further research work on parasitic infections in wild boars in Prymorye is necessary due to the high prevalence of helminthes in wild boars.

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Impact of patient safety on outcomes. From prevention to the treatment of post-intensive care syndrome.

Survivors of critical illness may present physical, psychological, or cognitive symptoms after hospital discharge, encompassed within what is known as post-intensive care syndrome. These alterations result from both the critical illness itself and the medical interventions surrounding it. For its prevention, the implementation of the ABCDEF bundle (Assess/treat pain, Breathing/awakening trials, Choice of sedatives, Delirium reduction, Early mobility and exercise, Family) has been proposed, along with additional strategies grouped under the acronym GHIRN (Good communication, Handout materials, Redefined ICU architectural design, Respirator, Nutrition). In addition to these preventive measures during the ICU stay, high-risk patients should be identified for subsequent follow-up through multidisciplinary teams coordinated by Intensive Care Medicine Departments.