Metagenomic analysis of microbial consortia native to the Amazon, Highlands, and Galapagos regions of Ecuador with potential for wastewater remediation.

Native microbial consortia have been proposed for biological wastewater treatment, but their diversity and function remain poorly understood. This study investigated three native microalgae-bacteria consortia collected from the Amazon, Highlands, and Galapagos regions of Ecuador to assess their metagenomes and wastewater remediation potential. The consortia were evaluated for 12 days under light (LC) and continuous dark conditions (CDC) to measure their capacity for nutrient and organic matter removal from synthetic wastewater (SWW). Overall, all three consortia demonstrated higher nutrient removal efficiencies under LC than CDC, with the Amazon and Galapagos consortia outperforming the Highlands consortium in nutrient removal capabilities. Despite differences in α- and ß-diversity, microbial species diversity within and between consortia did not directly correlate with their nutrient removal capabilities. However, all three consortia were enriched with core taxonomic groups associated with wastewater remediation activities. Our analyses further revealed higher abundances for nutrient removing microorganisms in the Amazon and Galapagos consortia compared with the Highland consortium. Finally, this study also uncovered the contribution of novel microbial groups that enhance wastewater bioremediation processes. These groups have not previously been reported as part of the core microbial groups commonly found in wastewater communities, thereby highlighting the potential of investigating microbial consortia isolated from ecosystems of megadiverse countries like Ecuador.

Prophage terminase with tRNase activity sensitizes Salmonella enterica to oxidative stress.

Phage viruses shape the evolution and virulence of their bacterial hosts. The Salmonella enterica genome encodes several stress-inducible prophages. The Gifsy-1 prophage terminase protein, whose canonical function is to process phage DNA for packaging in the virus head, unexpectedly acts as a transfer ribonuclease (tRNase) under oxidative stress, cleaving the anticodon loop of tRNALeu. The ensuing RNA fragmentation compromises bacterial translation, intracellular survival, and recovery from oxidative stress in the vertebrate host. S. enterica adapts to this transfer RNA (tRNA) fragmentation by transcribing the RNA repair Rtc system. The counterintuitive translational arrest provided by tRNA cleavage may subvert prophage mobilization and give the host an opportunity for repair as a way of maintaining bacterial genome integrity and ultimately survival in animals.

Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization.

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

Native microalgal-bacterial consortia from the Ecuadorian Amazon region: an alternative to domestic wastewater treatment.

In low-middle income countries (LMIC), wastewater treatment using native microalgal-bacterial consortia has emerged as a cost-effective and technologically-accessible remediation strategy. This study evaluated the effectiveness of six microalgal-bacterial consortia (MBC) from the Ecuadorian Amazon in removing organic matter and nutrients from non-sterilized domestic wastewater (NSWW) and sterilized domestic wastewater (SWW) samples. Microalgal-bacterial consortia growth, in NSWW was, on average, six times higher than in SWW. Removal rates (RR) for NH4 +- N and PO4 3--P were also higher in NSWW, averaging 8.04 ± 1.07 and 6.27 ± 0.66 mg L-1 d-1, respectively. However, the RR for NO3 - -N did not significantly differ between SWW and NSWW, and the RR for soluble COD slightly decreased under non-sterilized conditions (NSWW). Our results also show that NSWW and SWW samples were statistically different with respect to their nutrient concentration (NH4 +-N and PO4 3--P), organic matter content (total and soluble COD and BOD5), and physical-chemical parameters (pH, T, and EC). The enhanced growth performance of MBC in NSWW can be plausibly attributed to differences in nutrient and organic matter composition between NSWW and SWW. Additionally, a potential synergy between the autochthonous consortia present in NSWW and the native microalgal-bacterial consortia may contribute to this efficiency, contrasting with SWW where no active autochthonous consortia were observed. Finally, we also show that MBC from different localities exhibit clear differences in their ability to remove organic matter and nutrients from NSWW and SWW. Future research should focus on elucidating the taxonomic and functional profiles of microbial communities within the consortia, paving the way for a more comprehensive understanding of their potential applications in sustainable wastewater management.

Anaerobic respiration of host-derived methionine sulfoxide protects intracellular Salmonella from the phagocyte NADPH oxidase.

Intracellular Salmonella experiencing oxidative stress downregulates aerobic respiration. To maintain cellular energetics during periods of oxidative stress, intracellular Salmonella must utilize terminal electron acceptors of lower energetic value than molecular oxygen. We show here that intracellular Salmonella undergoes anaerobic respiration during adaptation to the respiratory burst of the phagocyte NADPH oxidase in macrophages and in mice. Reactive oxygen species generated by phagocytes oxidize methionine, generating methionine sulfoxide. Anaerobic Salmonella uses the molybdenum cofactor-containing DmsABC enzymatic complex to reduce methionine sulfoxide. The enzymatic activity of the methionine sulfoxide reductase DmsABC helps Salmonella maintain an alkaline cytoplasm that supports the synthesis of the antioxidant hydrogen sulfide via cysteine desulfuration while providing a source of methionine and fostering redox balancing by associated dehydrogenases. Our investigations demonstrate that nontyphoidal Salmonella responding to oxidative stress exploits the anaerobic metabolism associated with dmsABC gene products, a pathway that has accrued inactivating mutations in human-adapted typhoidal serovars.

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. RESULTS: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. CONCLUSIONS: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor ß signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Sulfur-Doped g-C3N4 Heterojunctions for Efficient Visible Light Degradation of Methylene Blue.

The discharge of synthetic dyes from different industrial sources has become a global issue of concern. Enormous amounts are released into wastewater each year, causing concerns due to the high toxic consequences. Photocatalytic semiconductors appear as a green and sustainable form of remediation. Among them, graphitic carbon nitride (g-C3N4) has been widely studied due to its low cost and ease of fabrication. In this work, the synthesis, characterization, and photocatalytic study over methylene blue of undoped, B/S-doped, and exfoliated heterojunctions of g-C3N4 are presented. The evaluation of the photocatalytic performance showed that exfoliated undoped/S-doped heterojunctions with 25, 50, and 75 mass % of S-doped (g-C3N4) present enhanced activity with an apparent reaction rate constant (kapp) of 1.92 × 10-2 min-1 for the 75% sample. These results are supported by photoluminescence (PL) experiments showing that this heterojunction presents the less probable electron-hole recombination. UV-vis diffuse reflectance and valence band-X-ray photoelectron spectroscopy (VB-XPS) allowed the calculation of the band-gap and the valence band positions, suggesting a band structure diagram describing a type I heterojunction. The photocatalytic activities calculated demonstrate that this property is related to the surface area and porosity of the samples, the semiconductor nature of the g-C3N4 structure, and, in this case, the heterojunction that modifies the band structure. These results are of great importance considering that scarce reports are found concerning exfoliated B/S-doped heterojunctions.

Understanding the Feature Space and Decision Boundaries of Commercial WAFs Using Maximum Entropy in the Mean.

The security of a network requires the correct identification and characterization of the attacks through its ports. This involves the follow-up of all the requests for access to the networks by all kinds of users. We consider the frequency of connections and the type of connections to a network, and determine their joint probability. This leads to the problem of determining a joint probability distribution from the knowledge of its marginals in the presence of errors of measurement. Mathematically, this consists of an ill-posed linear problem with convex constraints, which we solved by the method of maximum entropy in the mean. This procedure is flexible enough to accommodate errors in the data in a natural way. Also, the procedure is model-free and, hence, it does not require fitting unknown parameters.

Effectiveness of Tranexamic Acid in the Postoperative Period in Body Contour Surgery: Randomized Clinical Trial.

Background: Tranexamic acid (TXA) is used to reduce bleeding in body contouring procedures; however, there are no studies that show the effectiveness of TXA when it is also used in the immediate postoperative period. Methods: A controlled, randomized, parallel, and open-label clinical trial was carried out in adult patients undergoing liposculpture and/or abdominoplasty. A control group administering presurgical TXA and a study group with presurgical and postsurgical TXA were formed. The decrease in hemoglobin and the incidence of blood transfusions between both groups were compared as well as the possible adverse effects of TXA. Results: Four hundred twenty-seven subjects were included, 208 (48.7%) in the control group and 219 (51.3%) in the study group. The median age was 34 years (interquartile range 28-42). Median postoperative hemoglobin levels at 24 hours were similar in both groups (study 11.3 g/dL versus control 11.1 g/dL, P = 0.07); however, at 72 hours, postoperative hemoglobin was higher in the study group versus control (10.8 versus 10.0 g/dL, P ≤ 0.001). The incidence of transfusions at 72 hours was 1.8% in the study group and 8.6% in the control group, for a risk ratio of 0.21 (95% confidence interval 0.07-0.61). There were no adverse or thromboembolic events. Conclusion: TXA proved to be more effective in reducing intra- and postsurgical bleeding and the need for transfusions, when used preoperatively and continued for 48 hours after surgery, than when used only preoperatively, without reporting adverse or thromboembolic effects.

Seminal Plasma Proteins Associated with The Fertility of Brahman Bulls in The Colombian Low Tropics.

The sperm interacts with seminal plasma proteins during its transport through the female reproductive tract to reach the oocyte. Seminal plasma proteins have been associated as biomarkers of fertility in bovine males, while two-dimensional electrophoresis in polyacrylamide gels under denaturing conditions (2D-PAGE) is a useful technique for their separation, allowing their subsequent analysis with the aid of specialised software. Brahman bulls are known for their tolerance to tropical conditions such as low-quality pastures, high temperatures, and relative humidity as well as moderate resistance to infestations by parasites and insects. The present study describes the two-dimensional electrophoretic profiles of the seminal plasma proteins in the rainy and dry seasons, associating them with the fertility of Brahman bulls in the Colombian Orinoquía in a 90-days breeding season and a single-sire mating system (1 bull per 50 Brahman cows) with 60 consecutive days of rest. The fertility-related seminal plasma protein spots increased in the dry season. Likewise, a meaningful relationship was found between the protein spots that possibly coincide with the Binder of Sperm Proteins. It was also found that bulls with the highest percentages of pregnancy also had similarities in their 2D seminal plasma maps. We conclude that the seminal plasma protein profile of Brahman bulls raised in the Colombian low tropic changes between rainy and dry seasons, and such changes may influence the reproductive performance of those animals.

Factors associated with adolescent pregnancy in Maharashtra, India: a mixed-methods study.

Reducing the adolescent birth rate is paramount in achieving the health-related Sustainable Development Goals, given that pregnancy and childbirth are the leading cause of mortality among young women aged 15-19. This study aimed to explore predictors of adolescent pregnancy among girls aged 13-18 years in Maharashtra, India, during the COVID-19 pandemic. Using a mixed-methods approach, primary data were gathered from two regions in Maharashtra between February and April 2022. Quantitative data from face-to-face interviews with 3049 adolescent girls assessed various household, social, and behavioural factors, as well as the socioeconomic and health impacts of COVID-19. Qualitative data from seven in-depth interviews were analysed thematically. The findings reveal that girls from low socioeconomic backgrounds face a higher likelihood of adolescent pregnancy. Multivariable analysis identified several factors associated with increased risk, including older age, being married, having more sexual partners, and experiencing COVID-19-related economic vulnerability. On the other hand, rural residence, secondary and higher secondary education of the participants, and higher maternal education were associated with a decreased likelihood of adolescent pregnancy. In the sub-sample of 565 partnered girls, partner's emotional abuse also correlated with higher rates of adolescent pregnancy. Thematic analysis of qualitative data identified four potential pathways leading to adolescent pregnancy: economic hardships and early marriage; personal safety, social norms, and early marriage; social expectations; and lack of knowledge on contraceptives. The findings underscore the significance of social position and behavioural factors and the impact of external shocks like the COVID-19 pandemic in predicting adolescent pregnancy in Maharashtra, India.Plain Language Summary: Adolescent pregnancy is an important health issue for young girls. In South Asia, one out of every five adolescent girls becomes a mother before turning 18, and in India, around 9% of girls aged 15-19 get pregnant yearly. This study focused on understanding the factors associated with adolescent pregnancy in Maharashtra, India, especially after the COVID-19 pandemic. We collected information from both urban and rural areas in Maharashtra. A total of 3049 adolescent girls participated in a survey, and seven girls participated in detailed interviews. Our analysis showed that factors like older age, being married, having multiple sexual partners, and experiencing economic difficulties due to COVID-19 increased the chances of adolescent pregnancy. On the other hand, living in rural areas, higher education for both the girls and their mothers reduced the likelihood of adolescent pregnancy. Qualitative analysis revealed that economic challenges, concerns about safety and societal norms, early marriage, societal expectations, and lack of knowledge about contraceptives could contribute to adolescent pregnancy in Maharashtra.

Aortic valve reconstruction surgery with Ozaki technique: initials results from a single center / Cirugía de reconstrucción de válvula aórtica con técnica de Ozaki: resultados iniciales en un centro de referencia

Abstract Background: Aortic valve (AV) replacement is the gold standard treatment for severe symptomatic AV disease. Recently, AV reconstruction surgery (Ozaki procedure) emerges as a surgical alternative with good results in the medium term. Methods: We retrospectively analyzed 37 patients who underwent AV reconstruction surgery between January 2018 and June 2020 in a national reference center in Lima, Peru. The median age was 62 years, interquartile range (IQR: 42-68). The main indication for surgery was AV stenosis (62.2%), in most cases due to bicuspid valve (19 patients, 51.4%). Twenty-two (59.4%) patients had another pathology with surgical indication associated to AV disease, 8 (21.6%) had dilatation of the ascending aorta with indication for replacement. Results: One in-hospital death occurred (1/38, 2.7%) due to perioperative myocardial infarction. There was a significant reduction in the medians of the peak (70 mmHg, CI 95% = 50.03-79.86 vs. 14 mmHg, CI 95% = 11.93-17.5, p < 0.0001) and mean (45.5 mmHg CI 95% = 30.6-49.68 vs. 7 mmHg, CI 95% = 5.93-9.6, p < 0.0001) AV gradients when we compared baseline characteristics with first 30-days results. In an average of 19 (± 8.9) months of follow-up, survival, reoperation-free survival for valve dysfunction, and survival free of AV insufficiency ≥ II were 97.3%, 100% and 91.9%, respectively. Significant reduction in the medians of the peak and mean AV gradients was maintained. Conclusions: AV reconstruction surgery showed optimal results in term of mortality, reoperation-free survival, and hemodynamic characteristics of the neo-AV.

Resumen Introducción: El reemplazo de la válvula aórtica es el tratamiento de elección para la valvulopatía aórtica severa sintomática. Recientemente, la cirugía de reconstrucción valvular aórtica (procedimiento de Ozaki) emerge como una alternativa quirúrgica con buenos resultados a mediano plazo. Métodos: Analizamos retrospectivamente 37 pacientes intervenidos de reconstrucción de válvula aórtica entre enero de 2018 y junio de 2020 en un centro de referencia nacional en Lima, Perú. La mediana de edad fue de 62 años (rango intercuartílico: 42-68). La estenosis de la válvula fue la principal indicación de cirugía (62.2%), en la mayoría de los casos por válvula bicúspide (19 pacientes, 51.4%). 22 (59.4%) pacientes presentaban otra patología con indicación de cirugía, 8 (21.6%) presentaban dilatación de la aorta ascendente con indicación de reemplazo. Resultados: La mortalidad intrahospitalaria fue de 1/38, 2.7%, por infarto de miocardio perioperatorio. Hubo una reducción significativa en las medianas del gradiente máximo (70 mmHg, IC 95% = 50.03-79.86 vs. 14 mmHg, IC 95% = 11.93-17.5, p < 0.0001) y gradiente medio (45.5 mmHg IC 95% = 30.6-49.68 vs. 7 mmHg, IC 95% = 5.93-9.6, p < 0.0001) de la válvula aórtica cuando comparamos las características basales con los resultados de los primeros 30 días. En una media de 19 (± 8.9) meses de seguimiento la sobrevida fue del 97.3%; la sobrevida libre de reoperación por disfunción valvular, 100% y la sobrevida libre de insuficiencia aórtica ≥ II, 91.9%, respectivamente. Se mantuvo una reducción significativa en las medianas de los gradientes máximo y medio de la válvula aórtica. Conclusiones: La cirugía de reconstrucción de válvula aórtica con pericardio autólogo mostró resultados óptimos en términos de mortalidad, supervivencia libre de reoperación y características hemodinámicas de la neo-válvula.

Functional brain connectivity indexes derived from low-density EEG of pre-implanted patients as VNS outcome predictors.

Objective. In 1/3 of patients, anti-seizure medications may be insufficient, and resective surgery may be offered whenever the seizure onset is localized and situated in a non-eloquent brain region. When surgery is not feasible or fails, vagus nerve stimulation (VNS) therapy can be used as an add-on treatment to reduce seizure frequency and/or severity. However, screening tools or methods for predicting patient response to VNS and avoiding unnecessary implantation are unavailable, and confident biomarkers of clinical efficacy are unclear.Approach. To predict the response of patients to VNS, functional brain connectivity measures in combination with graph measures have been primarily used with respect to imaging techniques such as functional magnetic resonance imaging, but connectivity graph-based analysis based on electrophysiological signals such as electroencephalogram, have been barely explored. Although the study of the influence of VNS on functional connectivity is not new, this work is distinguished by using preimplantation low-density EEG data to analyze discriminative measures between responders and non-responder patients using functional connectivity and graph theory metrics.Main results. By calculating five functional brain connectivity indexes per frequency band upon partial directed coherence and direct transform function connectivity matrices in a population of 37 refractory epilepsy patients, we found significant differences (p< 0.05) between the global efficiency, average clustering coefficient, and modularity of responders and non-responders using the Mann-Whitney U test with Benjamini-Hochberg correction procedure and use of a false discovery rate of 5%.Significance. Our results indicate that these measures may potentially be used as biomarkers to predict responsiveness to VNS therapy.

The methylglyoxal pathway is a sink for glutathione in Salmonella experiencing oxidative stress.

Salmonella suffer the cytotoxicity of reactive oxygen species generated by the phagocyte NADPH oxidase in the innate host response. Periplasmic superoxide dismutases, catalases and hydroperoxidases detoxify superoxide and hydrogen peroxide (H2O2) synthesized in the respiratory burst of phagocytic cells. Glutathione also helps Salmonella combat the phagocyte NADPH oxidase; however, the molecular mechanisms by which this low-molecular-weight thiol promotes resistance of Salmonella to oxidative stress are currently unknown. We report herein that Salmonella undergoing oxidative stress transcriptionally and functionally activate the methylglyoxal pathway that branches off from glycolysis. Activation of the methylglyoxal pathway consumes a substantial proportion of the glutathione reducing power in Salmonella following exposure to H2O2. The methylglyoxal pathway enables Salmonella to balance glucose utilization with aerobic respiratory outputs. Salmonella take advantage of the metabolic flexibility associated with the glutathione-consuming methylglyoxal pathway to resist reactive oxygen species generated by the enzymatic activity of the phagocyte NADPH oxidase in macrophages and mice. Taken together, glutathione fosters oxidative stress resistance in Salmonella against the antimicrobial actions of the phagocyte NADPH oxidase by promoting the methylglyoxal pathway, an offshoot metabolic adaptation of glycolysis.

Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy.

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.

Enhanced vs conventional monofocal intraocular lens clinical results in patients with cataract: randomized clinical trial.

PURPOSE: To compare clinical outcomes between an enhanced and a conventional monofocal intraocular lens (IOL) after cataract surgery. SETTING: Ophthalmology Unit, Hospital del Salvador, University of Chile (tertiary care hospital). DESIGN: Double-masked, prospective randomized controlled trial. METHODS: 66 healthy adults with corneal astigmatism less than 1.50 diopters and axial length between 21 and 27 mm were randomly allocated (1:1) for bilateral phacoemulsification with either an enhanced monofocal IOL (ICB00) or a conventional aspheric monofocal IOL (ZCB00) implant. The refractive target was emmetropia in both eyes. Visual acuities, defocus curves, Catquest-9SF, and quality of vision (QoV) were measured 3 months postoperatively. RESULTS: Binocular uncorrected intermediate visual acuity was improved in patients implanted with the enhanced monofocal lens (0.37 ± 0.12) compared with the conventional monofocal (0.45 ± 0.10) ( P < .01). There were no significant differences in corrected distance visual acuity (CDVA), Catquest-9SF, or QoV scores. CONCLUSIONS: The enhanced monofocal IOL provided 1 additional line of intermediate visual acuity after cataract surgery. There was no significant change in either CDVA or QoV.