Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection.

Background: Limited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome. Methods: PCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months. Comparisons based on vaccination status alone and unsupervised hierarchical clustering were performed. A second cohort of vaccinated Omicron patients were evaluated acutely and at ten months. Results: Acutely, unvaccinated patients manifested overexpression of proteins involved in immune and inflammatory responses, while vaccinated patients exhibited adaptive immune responses without significant inflammation. At three and ten months, only unvaccinated patients had diminished but sustained inflammatory (C3b, CCL15, IL17RE) and immune responses (DEFA5,TREM1). Both groups had underexpression of pathways essential for cellular function, signaling, and angiogenesis (AKT1, MAPK14, HSPB1) across phases. Unsupervised clustering, based on protein expression, identified four groups of patients with variable vaccination rates demonstrating that additional clinical factors influence the plasma proteome. The proteome of vaccinated Omicron patients did not differ from vaccinated pre-Omicron patients. Conclusions: Vaccination attenuates the inflammatory response to SARS-CoV-2 infection across phases. However, at ten months after symptom onset, changes in the plasma proteome persist in both vaccinated and unvaccinated individuals, which may be relevant to post-acute sequelae of SARS-CoV-2 and other viral infections associated with post-acute infection syndromes.

Acute coronary syndrome due to coronary vasospasm: a case report.

Coronary vasospasm can lead to decreased cardiac perfusion and result in acute coronary syndrome. Here is a case of a 49-year-old man presented to the emergency department with epigastric pain and nausea with normal initial electrocardiogram. However, 6 h later, the patient experienced severe chest pain prompting a repeat electrocardiogram demonstrating inferior ST-segment elevation with troponin I levels peaked at 1.2 ng/ml (normal range: 0.00-0.02 ng/ml). Coronary angiography revealed angiographic stenosis in the left circumflex territory of a left dominant system which resolved with intracoronary nitroglycerin administration indicating ischemia with nonobstructive coronary arteries secondary to coronary vasospasm. He was discharged on isosorbide mononitrate and amlodipine therapy and had no recurrence of symptoms during follow-up.

[Box: see text].

Effective Management of a Giant Deforming Pleomorphic Adenoma With Airway Displacement in a 93-Year-Old Patient: A Case Report.

Benign salivary gland tumors are a rare and diverse group of neoplasms with significant variations in their site of origin, histological features, and biological behavior. This report describes the case of a 93-year-old woman with a markedly enlarged left cervical mass. Physical inspection uncovered a tumor of approximately 32 x 30 cm, featuring necrotic and ulcerated areas. The neoplasm, diagnosed as a pleomorphic adenoma (PA) through prior biopsies, had been growing gradually over fifteen years, with delayed surgical intervention due to concerns about her age and the tumor's size. Preoperative contrast-enhanced CT imaging showed a large left-sided cervical mass in close proximity to the airway, but without displacement or infiltration into major structures. An elective surgical approach was undertaken, involving complete resection of the giant PA, confirmed by histopathological evaluation. During the first month of postoperative follow-up, the patient experienced partial facial nerve paralysis but showed no evidence of tumor recurrence. Despite the tumor's considerable size, proximity to the airway, and the patient's advanced age, curative surgical intervention proved feasible. This case underscores that, with meticulous preoperative planning and careful surgical execution, age should not be a contraindication for surgery.

Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the CAMEO-DAPA Trial.

BACKGROUND: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. METHODS: In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. RESULTS: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). CONCLUSIONS: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Association of kidney function with SGLT2 inhibitor discontinuation among United States Veterans.

BACKGROUND: The impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on cardiovascular disease and chronic kidney disease (CKD) may be limited if discontinued in persons with CKD. We sought to determine whether CKD at SGLT2i initiation was associated with subsequent discontinuation. METHODS: This cohort study used electronic health record data of patients who initiated SGLT2i in the Veterans Health Administration from January 2017 through December 2021. The primary exposure was eGFR category at the time of SGLT2i initiation. The risk of SGLT2i discontinuation, defined by a provider order or expiration of an SGLT2i prescription without resumption in the following 180 days, was estimated using proportional hazards models with inverse probability weights for censoring due to death. Analyses were stratified by year of SGLT2i initiation. RESULTS: Among the 222,772 patients initiating an SGLT2i during the study period, median age was 68 (IQR: 60-73) years, 95% were male, and median (IQR) eGFR was 73 (58, 89) mL/min/1.73m2. Median follow-up was 1.6 years; 32% experienced SGLT2i discontinuation. Cumulative risk of discontinuation at one year was 21% to 27% across calendar years; approximately 41% of these discontinuations occurred within the first three months. There was a graded association between lower baseline eGFR and greater risk of discontinuation; this association attenuated across calendar years. Those initiating an SGLT2i in 2017 with baseline eGFR of 45-59 and 30-44 had 1.34- (95%CI: 1.21-1.49) and 2.04-fold (95%CI: 1.58-2.63) risks of discontinuation, respectively, compared to those with eGFR ≥60 ml/min/1.73m2. These hazard ratios reduced to 1.05 (95%CI: 1.02-1.10) and 1.20 (95%CI: 1.14-1.26), respectively, in those initiated in 2021. CONCLUSIONS: A substantial proportion of patients experience SGLT2i discontinuation within a year of initiation. Persons with lower eGFR had higher discontinuation rates; however, this trend attenuated over time. Additional studies identifying determining factors of discontinuation are needed to fully realize the benefits of SGLT2i.

How to assess survival prognosis in patients hospitalized for community-acquired pneumonia in 2024?

PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is increasingly recognized as a complex, multisystemic disease with the potential to cause both acute and long-term sequelae, significantly impacting patient mortality rates. In this manuscript, the authors review the current methodologies for assessing mortality risk among CAP patients. RECENT FINDINGS: The most common prediction scores for ICU care and short-term mortality include Pneumonia Severity Index (PSI), CURB-65, SMART COP, SCAP, and ATS/IDSA criteria. These models have clinical utility in the prediction of short-term mortality, but they have significant limitations in addressing long-term mortality. For patients who are discharged alive from the hospital, we do not have scores to predict long term mortality. SUMMARY: The development of an optimal prognostic tool for postacute sequelae of CAP is imperative. Such a tool should identify specific populations at increased risk. Moreover, accurately identifying at-risk populations is essential for their inclusion in clinical trials that evaluate potential therapies designed to improve short and long-term clinical outcomes in patients with CAP.

ESBL-producing Escherichia coli prevalence and sharing across seabirds of central Chile.

Antimicrobial resistance (AMR) is a major global public threat, now largely reported in natural environments. Seabirds are carriers of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli), but different foraging and breeding behaviour could impact ESBL-E. coli circulation. We compared the prevalence and genetic determinants of ESBL-E. coli from resident Kelp gulls (Larus dominicanus, Ld), migratory Franklin's gulls (Larus pipixcan, Lp), and endemic Peruvian pelicans (Pelecanus thagus, Pt) from the Humboldt Current Ecosystem (HCE) of central Chile. From 2020 to 2022, we collected 699 fresh faecal samples (Ld = 449, Lp = 116, Pt = 134), and isolated 271 ESBL-E. coli (39 %). Whole-genome-sequencing (WGS) was performed on 85 E. coli selected isolates to identify their Sequence Type (ST), AMR genes, virulence genes, mobile genetic elements (MGE), and to assess potential interspecies transmission. ESBL-genes were detected in the remaining ESBL-E. coli isolates by PCR. ESBL-E. coli prevalence in Ld (46 % [CI: 42-51 %]) and Pt (34 % [CI: 27-43 %]) was higher than in Lp (15 % [CI: 9-22 %]). WGS revealed 41 ESBL-E. coli STs including pandemic clones ST10, ST58, ST131 and ST410. The blaCTX-M-1 and blaCTX-M-15 genes were the most prevalent among ESBL genes, and were mostly associated with MGE IncI1-I(Alpha) and ISEc9. We also report the pAmpC blaCMY-2 gene associated to MGE Inc1-I(Alpha) and IS640 in two E. coli from a Ld and a Lp. Eight ESBL-E. coli of the same ST were shared by at least two seabird species, including ST10 (Ld and Pt); ST88, ST410 and ST617 (Pt and Lp); ST38, ST58, ST131, and SST1722 (three species). Single nucleotide polymorphism (SNP) phylogenetic analyses of ST38, ST617 and ST1722 showed a low difference of SNPs between STs found in different seabird species, suggesting ESBL-E. coli clonal exchanges. Our results highlight ESBL-E. coli dissemination across seabirds of the HCE, including species that unusually forage on human waste like pelicans.

Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC.

BACKGROUND AND AIMS: Simultaneous inhibition of the TGF-ß and programmed cell death 1 ligand 1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death 1 ligand 1, was evaluated in patients with advanced HCC. APPROACH AND RESULTS: In this global, open-label, phase I study (NCT02517398), patients with programmed cell death 1 ligand 1-unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200 mg every 2 weeks in a dose-escalation (n = 38) or dose-expansion (n = 68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was the best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. Secondary endpoints included investigator-assessed best overall response, safety, and pharmacokinetics. Median follow-up times (range) were 41.4 (39.8-44.2) and 38.6 (33.5-39.7) months in the dose-escalation and dose-expansion cohorts, respectively. The objective response rate was below the prespecified 20% objective response rate threshold set to evaluate the efficacy of bintrafusp alfa in both cohorts (10.5% and 8.8%, respectively). Median overall survival and progression-free survival, respectively, were 13.8 and 1.5 months in the dose-escalation cohort and 13.5 and 1.4 months in the dose-expansion cohort. Treatment-related adverse events occurred in 78.9% and 64.7% of patients in the respective cohorts (grade ≥3 in 18.4% and 25.0% of patients). CONCLUSIONS: Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.

Prognostic Significance and Biologic Associations of Senescence-Associated Secretory Phenotype Biomarkers in Heart Failure.

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach. METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism. CONCLUSIONS: Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.

Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. CONCLUSIONS: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Endothelin-1 down-regulates nuclear factor erythroid 2-related factor-2 and contributes to perivascular adipose tissue dysfunction in obesity.

Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.

Rationale and Design of the Latin-American Registry of Peripheral Interventions: Insights From SOLACI Peripheral.

Background: Chronic limb-threatening ischemia (CLTI) represents the most advanced stage of lower extremity peripheral artery disease (PAD). The aim of this manuscript is to provide an overview of the demographic and clinical characteristics of patients with lower-limb peripheral artery disease, as well as the procedural and technical aspects of peripheral endovascular interventions in Latin-America. Methods: The SOLACI peripheral registry is a prospective, multi-center, observational, and hospital-based registry of patients with lower-limb PAD, who are treated with endovascular interventions across Latin American countries. Results: A total of 1057 independent procedures (997 patients) were analyzed in this report. The most common clinical presentation was CLTI (61.2%): Advanced stage of the disease was common, and the symptomatic classification was predominately Rutherford V (minor tissue loss) in 37.6%. Index endovascular procedures mainly treated femoral-popliteal and infrapopliteal regions. Disease extending across multiple vascular territories was common and 27.6% of patients underwent angioplasty of multiple regions during the same procedure. There was a high prevalence of cardiovascular risk factors and concomitant comorbidities: hypertension (84.5%), dyslipidemia 67.4%), diabetes mellitus (64.7%), myocardial infarction (17%) and stroke (8.4%). Major adverse events during hospitalization included death from any cause (1.3%), cardiovascular death (0.7 %), myocardial infarction (0.4%), stroke (0.1%) and bleeding (0.8%). Conclusions: Real-world data on lower limb-PAD in Latin American countries will help us identify unmet needs and generate evidence-based recommendations to facilitate the development of more effective preventive and treatment strategies according to each country's necessities and resources.

Targeting the dependence on PIK3C3-mTORC1 signaling in dormancy-prone breast cancer cells blunts metastasis initiation.

Halting breast cancer metastatic relapses following primary tumor removal and the clinical dormant phase, remains challenging, due to a lack of specific vulnerabilities to target during dormancy. To address this, we conducted genome-wide CRISPR screens on two breast cancer cell lines with distinct dormancy properties: 4T1 (short-term dormancy) and 4T07 (prolonged dormancy). We discovered that loss of class-III PI3K, Pik3c3, revealed a unique vulnerability in 4T07 cells. Surprisingly, dormancy-prone 4T07 cells exhibited higher mTORC1 activity than 4T1 cells, due to lysosome-dependent signaling occurring at the cell periphery. Pharmacological inhibition of Pik3c3 counteracted this phenotype in 4T07 cells, and selectively reduced metastasis burden only in the 4T07 dormancy-prone model. This mechanism was also detected in human breast cancer cell lines in addition to a breast cancer patient-derived xenograft supporting that it may be relevant in humans. Our findings suggest dormant cancer cell-initiated metastasis may be prevented in patients carrying tumor cells that display PIK3C3-peripheral lysosomal signaling to mTORC1. Statement of Significance: We reveal that dormancy-prone breast cancer cells depend on the class III PI3K to mediate a constant peripheral lysosomal positioning and mTORC1 hyperactivity. Targeting this pathway might blunt breast cancer metastasis.

Prognostic Value of Cardio-Ankle Vascular Index for Cardiovascular and Kidney Outcomes: Systematic Review and Meta-Analysis.

Background: Arterial stiffness causes cardiovascular disease and target-organ damage. Carotid-femoral pulse wave velocity is regarded as a standard arterial stiffness metric. However, the prognostic value of cardio-ankle vascular index (CAVI), which is mathematically corrected for blood pressure, remains understudied. Objectives: The purpose of this study was to determine the association of CAVI with cardiovascular and kidney outcomes. Methods: PubMed, Scopus, and Web of Science were searched until May 6, 2023, for longitudinal studies reporting the association of CAVI with mortality, cardiovascular events (CVEs) (including death, acute coronary syndromes, stroke, coronary revascularization, heart failure hospitalization), and kidney function decline (incidence/progression of chronic kidney disease, glomerular filtration rate decline). Random-effects meta-analysis was performed. Studies were assessed with the "Quality in Prognostic Studies" tool. Results: Systematic review identified 32 studies (105,845 participants; follow-up range: 12-148 months). Variable cutoffs were reported for CAVI. The risk of CVEs was higher for high vs normal CAVI (HR: 1.46 [95% CI: 1.22-1.75]; P < 0.001; I2 = 41%), and per SD/unit CAVI increase (HR: 1.30 [95% CI: 1.20-1.41]; P < 0.001; I2 = 0%). Among studies including participants without baseline cardiovascular disease (primary prevention), higher CAVI was associated with first-time CVEs (high vs normal: HR: 1.60 [95% CI: 1.15-2.21]; P = 0.005; I2 = 65%; HR per SD/unit increase: 1.28 [95% CI: 1.12-1.47]; P < 0.001; I2 = 18%). There was no association between CAVI and mortality (HR = 1.31 [0.92-1.87]; P = 0.130; I2 = 53%). CAVI was associated with kidney function decline (high vs normal: HR = 1.30 [1.18-1.43]; P < 0.001; I2 = 38%; HR per SD/unit increase: 1.12 [95% CI: 1.07-1.18]; P < 0.001; I2 = 0%). Conclusions: Higher CAVI is associated with incident CVEs, and this association is present in the primary prevention setting. Elevated CAVI is associated with kidney function decline.

Comparative effectiveness of frame-based and mask-based Gamma Knife stereotactic radiosurgery in brain metastases: A 509 patient meta-analysis.

PURPOSE: Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. METHODS: Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. RESULTS: From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89-1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78-0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89-1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72-3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38-21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22-1.76, p = 0.37). CONCLUSION: Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions.

Pneumatophore CO2 effluxes decrease with increased salinity in mangrove forests of Yucatan, Mexico.

Although mangrove forests are great carbon sinks, they also release carbon dioxide (CO2) from soil, plants, and water through respiration. Many studies have focused on CO2 effluxes only from soils, but the role of biogenic structures such as pneumatophore roots has been poorly studied. Hence, CO2 effluxes from pneumatophores were quantified at sediment-air (non-flooded sediment) and water-air (flooded sediment) interfaces along a salinity gradient in three mangrove types (fringe, scrub, and basin) dominated by Avicennia germinans during the dry and rainy seasons in Yucatan, Mexico. Pneumatophore abundance explained up to 91% of CO2 effluxes for scrub, 87% for fringe, and 83% for basin mangrove forests at the water-air interface. Overall, CO2 effluxes were inversely correlated with temperature and salinity. The highest CO2 effluxes were in the fringe and the lowest were in the scrub mangrove forests. Flooding decreased CO2 effluxes from the dry to the rainy season in all mangrove forests. These results highlight the contribution of pneumatophores to mangrove respiration, and the need to include them in our current carbon budgets and models, but considering different exchange interfaces, seasons, and mangrove ecotypes.

Cutaneous Rosai-Dorfman disease with MAP2K1 mutation, initially mimicking an infection with parasitized histiocytes.

Rarely, Rosai-Dorfman disease (RDD) manifests exclusively in the skin, typically as nodules on the trunk and extremities. Recognition of characteristic histopathologic features enables diagnosis of RDD. A 55-year-old female presented with a 7-year history of cutaneous nodules involving the trunk and extremities. A prior skin biopsy specimen at a different institution had demonstrated a dense dermal lymphohistiocytic infiltrate with histiocytes containing GMS+ forms, favored to represent cryptococcal organisms, with a differential diagnosis including other infections with parasitized histiocytes. Despite antibiotic therapy, lesions persisted. After a presentation to our institution, a biopsy specimen showed a diffuse infiltrate, including histiocytes with voluminous pale cytoplasm with focal emperipolesis of inflammatory cells and S100 immunohistochemical positivity. Clinical and radiologic examinations did not identify significant extracutaneous involvement. A genetic study performed on the biopsy specimen identified a K57Q mutation of MAP2K1. The presence of this mutation correlated with prior reports of MAP2K1 mutation in classic RDD, thereby supporting our histopathologic diagnosis of RDD over an infectious process and further illuminating options for targeted therapies. At 3-year follow-up, the patient has been managed with a course of systemic corticosteroids and excision of bothersome lesions. Consideration of systemic therapy is ongoing.

Hematological and biochemical characterization of aging farm male rat strains in the National Center for Geriatrics and Gerontology.

Laboratory rats, like mice, are a type of animal commonly used in scientific investigations as well as in basic aging and geriatric research. The selection of a rat strain is an important first step in the planning and design of an experiment due to physiological, anatomical, and ethological variations in each strain, which may significantly modify the expected results. In the present study, we characterized age-related changes, from 3 months old (mo) to 24 mo, in three male rat strains commonly used in medical research: RccHan®ï¸:WIST (RccHan:WIST), F344/NSlc (F344), and Slc:SD Rat (SD). The body weight, water/food consumption, and survival rate of each strain were physiologically evaluated. Hematological and biochemical values were analyzed every three months. Hematological results showed a decrease in lymphocytes and increases in other leukocytes from 12 mo in F344 and SD rats. The incidence of hematological disorder was 10-15% in F344 and SD rats from 18 mo. Increases in hepatic biochemical parameters (alanine transaminase (GPT/ALT) and aspartate transaminase (GOT/AST)) and cytopathological parameters (creatine phosphokinase (CPK)) were observed in male F344 rats at 12 mo. Triglycerides (TG) serum levels were significantly elevated in the 12 mo RccHan:WIST rats, while Lipase (LIP) levels were significantly reduced in 24 mo. The present results revealed significant variations in hematological and biochemical values in the different laboratory male rat strains due to genetic and nutritional-metabolic factors specific to each strain.

Energy efficiency in medium-scale airports: Two Mexican airports as case of study.

Reducing energy consumption in the operation of airports has been identified as one of the approaches to achieve the commitments of the countries in reducing their greenhouse gas (GHG) emissions. The first step in this approach is the development of an energy diagnostic. However, multiple practical aspects remain unresolved when applying the existing methodologies to perform energy diagnostics, especially in the case of small and medium-scale airports. Seeking to address these issues, this work presents energy diagnostics of two Mexican international airports so that it can be used to carry out energy diagnostics in other airports with similar characteristics. Emphasis is given to identifying and prioritizing, from a sustainable point of view, the strategies to reduce energy consumption and GHG emissions. The Ciudad del Carmen Airport (CME) is located in a nearshore region with high ambient temperatures (27 °C) and humidities. It was found that in 2019, the CME airport consumed 123 MWh with an average of 577 Wh per passenger, with the HVAC system being the primary energy consumer. Critical strategies for the CME airport include photovoltaic systems and HVAC renovation. In contrast, the Puebla airport (PBC) is located in a region with comfortable ambient conditions (16 °C). In 2019, the PBC airport consumed 61.31 MWh/year and 442 Wh per passenger. The main strategies for PBC include expanding its photovoltaic energy generation system, employee awareness programs, and renewing the vehicle fleet with electric vehicles.

Longitudinal analysis of the lung proteome reveals persistent repair months after mild to moderate COVID-19.

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate. However, at 9 months, quantified radiographic abnormalities resolve in the majority of patients, and yet compared to healthy persons, all showed ongoing activation of cellular repair processes and depression of the renin-kallikrein-kinin, coagulation, and complement systems. This dissociation of prolonged reparative processes from symptom and radiographic resolution suggests that occult ongoing disruption of the lung proteome is underrecognized and may be relevant to recovery from other serious viral pneumonias.