A cross sectional study assessing steatotic liver disease in patients with systemic lupus erythematosus.

Patients with immune-mediated inflammatory diseases are prone to steatotic liver disease (SLD), which has been observed in patients with psoriasis and hidradenitis suppurativa. We aimed to assess whether systemic lupus erythematosus (SLE) was associated with SLD and to define factors associated with SLD in SLE. This was a cross-sectional study, we included 106 consecutive patients with SLE who were seen in the rheumatology clinic between June 2021 and March 2022 and we chose two sex-paired controls for each SLE. All the participants underwent FibroScan and anthropometric assessments. SLD was defined as a controlled attenuation parameter ≥ 275dB/m. Prevalence of SLD was lower in patients with SLE (21.7% vs 41.5%, p < 0.001). Patients with SLE and SLD had a lower frequency of hydroxychloroquine use (65% vs 84%, p = 0.04), and higher C3 levels [123mg/dl (IQR 102-136) vs 99mg/dl (IQR 78-121), p = 0.004]. Factors associated with SLD in SLE were body mass index (BMI), waist circumference, glucose, and C3; hydroxychloroquine use was a protective factor. On univariate analysis, SLE was associated with a reduced risk of SLD (OR 0.39, 95%CI 0.23-0.67); however, after adjusting for age, BMI, waist, glucose, triglycerides, high-density cholesterol, low-density cholesterol, leukocytes, and hydroxychloroquine, it was no longer associated (OR 0.43, 95%CI 0.10-1.91). In conclusion, the prevalence of SLD in patients with SLE was not higher than that in the general population, and SLE was not associated with SLD. The factors associated with SLD were anthropometric data, glucose, hydroxychloroquine, and C3 levels.

Occurrence of Guillain-Barré Syndrome in the Early Post-operative Period After an Urgent Liver Transplant.

Solid organ transplant recipients are prone to developing a wide range of complications associated with the procedure itself, as well as with immunosuppressants. Guillain-Barré syndrome, which is part of the spectrum of inflammatory neuropathies, is not expected to occur early after organ transplant when immunosuppression is at its highest point. We describe the clinical case of a patient who underwent an urgent liver transplant due to acute liver failure secondary to drug-induced liver injury and developed Guillain-Barré syndrome early after the transplant.

Sea cucumber (Holothuria glaberrima) intestinal microbiome dataset from Puerto Rico, generated by shotgun sequencing.

The sea cucumber (H. glaberrima) is a species found in the shallow waters near coral reefs and seagrass beds in Puerto Rico. To characterize the microbial taxonomic composition and functional profiles present in the sea cucumber, total DNA was obtained from their intestinal system, fosmid libraries constructed, and subsequent sequencing was performed. The diversity profile displayed that the most predominant domain was Bacteria (76.56 %), followed by Viruses (23.24 %) and Archaea (0.04 %). Within the 11 phyla identified, the most abundant was Proteobacteria (73.16 %), followed by Terrabacteria group (3.20 %) and Fibrobacterota, Chlorobiota, Bacteroidota (FCB) superphylum (1.02 %). The most abundant species were Porvidencia rettgeri (21.77 %), Pseudomonas stutzeri (14.78 %), and Alcaligenes faecalis (5.00 %). The functional profile revealed that the most abundant functions are related to transporters, MISC (miscellaneous information systems), organic nitrogen, energy, and carbon utilization. The data collected in this project on the diversity and functional profiles of the intestinal system of the H. glaberrima provided a detailed view of its microbial ecology. These findings may motivate comparative studies aimed at understanding the role of the microbiome in intestinal regeneration.

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Chylous ascites after associating liver partition and portal vein ligation for stage hepatectomy (ALPPS): overview and case report.

Chylous ascites is an uncommon pathology with low incidence following hepato-pancreato-biliary surgery, there are no cases reported in the international literature following the associating liver partition and portal vein ligation for stage hepatectomy (ALPPS) procedure. It is caused by abnormal intraperitoneal accumulation of lymph fluid in the abdominal cavity secondary to obstruction or injury to the chyle cistern or its tributaries. We describe the case of a 49-year-old woman diagnosed with colon cancer and liver metastasis. ALPPS was performed, on a first and second stage, presenting a high drainage output as well as change in the characteristics of the drainage fluid. The diagnosis of chylous ascites was confirmed by finding triglyceride levels in the drainage fluid at 300 mg/dL. Medical treatment was started based on a hyper-protein diet and fat restriction, supplemented with medium-chain triglycerides and somatostatin analog, with fistula resolution. It can be managed with medical treatment.

Chemical sensing of common microorganisms found in biopharmaceutical industries using MIR laser spectroscopy and multivariate analysis.

Mid-infrared laser spectroscopy was used to investigate common bacteria encountered in biopharmaceutical industries. The study involved the detection of bacteria using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Substrates similar to surfaces commonly used in biopharmaceutical industries were used as support media for the samples. Reflectance measurements were assisted by Multivariate Analysis (MVA) to assemble a powerful spectroscopic technique with classification and identification resources. The species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique's capability to discriminate from microorganisms of the same family. Principal Components Analysis and Partial Least Squares-Discriminant Analysis differentiated between the bacterial species, using QCL-GAP-MVA as the reference. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity.

Discovery of Conformationally Constrained ALK2 Inhibitors.

Despite decades of research on new diffuse intrinsic pontine glioma (DIPG) treatments, little or no progress has been made on improving patient outcomes. In this work, we explored novel scaffold modifications of M4K2009, a 3,5-diphenylpyridine ALK2 inhibitor previously reported by our group. Here we disclose the design, synthesis, and evaluation of a first-in-class set of 5- to 7-membered ether-linked and 7-membered amine-linked constrained inhibitors of ALK2. This rigidification strategy led us to the discovery of the ether-linked inhibitors M4K2308 and M4K2281 and the amine-linked inhibitors M4K2304 and M4K2306, each with superior potency against ALK2. Notably, M4K2304 and M4K2306 exhibit exceptional selectivity for ALK2 over ALK5, surpassing the reference compound. Preliminary studies on their in vivo pharmacokinetics, including blood-brain barrier penetration, revealed that these constrained scaffolds have favorable exposure and do open a novel chemical space for further optimization and future evaluation in orthotopic models of DIPG.

Gene expression during the development of Mycobacterium smegmatis biofilms on hydroxyapatite surfaces / Expresión génica durante el desarrollo de biopelículas de Mycobacterium smegmatis en superficies de hidroxiapatita

Bacterial biofilms are a consortium of bacteria that are strongly bound to each other and the surface on which they developed irreversibly. Bacteria can survive adverse environmental conditions and undergo changes when transitioning from a planktonic form to community cells. The process of mycobacteria adhesion is complex, involving characteristics and properties of bacteria, surfaces, and environmental factors; therefore, the formation of different biofilms is possible. Cell wall-, lipid-, and lipid transporter-related genes (glycopeptidolipids, GroEL1, protein kinase) are important in mycobacterial biofilm development. We investigated gene expression during in vitro development of Mycobacterium smegmatis biofilms on a hydroxyapatite (HAP) surface. Biofilm formation by M. smegmatis cells was induced for 1, 2, 3, and 5 days on the HAP surface. Mycobacteria on polystyrene generated an air–liquid interface biofilm, and on the fifth day, it increased by 35% in the presence of HAP. Six genes with key roles in biofilm formation were analyzed by real-time RT‒qPCR during the biofilm formation of M. smegmatis on both abiotic surfaces. The expression of groEL1, lsr2, mmpL11, mps, pknF, and rpoZ genes during biofilm formation on the HAP surface did not exhibit significant changes compared to the polystyrene surface. These genes involved in biofilm formation are not affected by HAP.(AU)

Different serum sodium assay, different model for end stage liver disease - sodium scores in patients awaiting liver transplant: A cross-sectional study.

INTRODUCTION AND AIMS: Sodium can be measured with direct or indirect methods; abnormal plasma total protein concentration can impact on sodium measured by indirect ion-selective electrodes (ISE). Serum sodium is an important item to determine the Model for End Stage Liver Disease Sodium (MELD-Na) score, commonly used for liver graft allocation. Patients with cirrhosis usually have hypoproteinemia. The aim of this study was to determine if there was a significant difference between the MELD-Na scores calculated based on the results of two different serum sodium ISE: indirect and direct. METHODS: This was a retrospective study; we included 166 patients that underwent liver transplant assessment, and that had paired (i.e. same date and time) direct and indirect sodium determinations. We calculated the MELD-Na scores with both sodium determinations, and we compared them. RESULTS: There was a significant difference between MELD-Na scores; the mean difference was 0.4±1.3. If MELD-Na score had been determined by the sodium measured by the direct ISE, 69 patients (42%) would have stayed in the same place on the waiting list, 67 patients (40%) would have moved up, and 30 patients (18%) would have moved down. CONCLUSIONS: There was a statistically significant difference between the MELD-Na scores calculated based on the two different sodium concentrations, which would theoretically result in changes in the order of the waiting list. This finding should prompt studies to assess if MELD-Na calculated based on direct methods has a better performance to predict clinically relevant outcomes.

Gene expression during the development of Mycobacterium smegmatis biofilms on hydroxyapatite surfaces.

Bacterial biofilms are a consortium of bacteria that are strongly bound to each other and the surface on which they developed irreversibly. Bacteria can survive adverse environmental conditions and undergo changes when transitioning from a planktonic form to community cells. The process of mycobacteria adhesion is complex, involving characteristics and properties of bacteria, surfaces, and environmental factors; therefore, the formation of different biofilms is possible. Cell wall-, lipid-, and lipid transporter-related genes (glycopeptidolipids, GroEL1, protein kinase) are important in mycobacterial biofilm development. We investigated gene expression during in vitro development of Mycobacterium smegmatis biofilms on a hydroxyapatite (HAP) surface. Biofilm formation by M. smegmatis cells was induced for 1, 2, 3, and 5 days on the HAP surface. Mycobacteria on polystyrene generated an air-liquid interface biofilm, and on the fifth day, it increased by 35% in the presence of HAP. Six genes with key roles in biofilm formation were analyzed by real-time RT‒qPCR during the biofilm formation of M. smegmatis on both abiotic surfaces. The expression of groEL1, lsr2, mmpL11, mps, pknF, and rpoZ genes during biofilm formation on the HAP surface did not exhibit significant changes compared to the polystyrene surface. These genes involved in biofilm formation are not affected by HAP.

Antimycobacterial Precatorin A Flavonoid Displays Antibiofilm Activity against Mycobacterium bovis BCG.

The aim of this study was to evaluate the potential antibiofilm activity of Rhynchosia precatoria (R. precatoria) compounds over Mycobacterium bovis BCG (M. bovis BCG) as a model for Mycobacterium tuberculosis (Mtb). We evaluated the antibiofilm activity as the ability to both inhibit biofilm formation and disrupt preformed biofilms (bactericidal) of R. precatoria compounds, which have been previously described as being antimycobacterials against Mtb. M. bovis BCG developed air-liquid interface biofilms with surface attachment ability and drug tolerance. Of the R. precatoria extracts and compounds that were tested, precatorin A (PreA) displayed the best biofilm inhibitory activity, as evaluated by biofilm biomass quantification, viable cell count, and confocal and atomic force microscopy procedures. Furthermore, its combination with isoniazid at subinhibitory concentrations inhibited M. bovis BCG biofilm formation. Nonetheless, neither PreA nor the extract showed bactericidal effects. PreA is the R. precatoria compound responsible for biofilm inhibitory activity against M. bovis BCG.

Canine Mammary Cancer: State of the Art and Future Perspectives.

Mammary cancer is the most frequently diagnosed neoplasia in women and non-spayed female dogs and is one of the leading causes of death in both species. Canines develop spontaneous mammary tumors that share a significant number of biological, clinical, pathological and molecular characteristics with human breast cancers. This review provides a detailed description of the histological, molecular and clinical aspects of mammary cancer in canines; it discusses risk factors and currently available diagnostic and treatment options, as well as remaining challenges and unanswered questions. The incidence of mammary tumors is highly variable and is impacted by biological, pathological, cultural and socioeconomic factors, including hormonal status, breed, advanced age, obesity and diet. Diagnosis is mainly based on histopathology, although several efforts have been made to establish a molecular classification of canine mammary tumors to widen the spectrum of treatment options, which today rely heavily on surgical removal of tumors. Lastly, standardization of clinical study protocols, development of canine-specific biological tools, establishment of adequate dog-specific disease biomarkers and identification of targets for the development of new therapies that could improve survival and have less adverse effects than chemotherapy are among the remaining challenges.

RING Program: The CFAR Diversity, Equity, and Inclusion Pathway Initiative.

BACKGROUND: Case Western Reserve University (CWRU)/University Hospitals Cleveland Medical Center in Cleveland, OH, and the University of Pittsburgh (Pitt) in Pittsburgh, PA, forged a strategic alliance to form the Rustbelt Center for AIDS Research. The Rustbelt Center for AIDS Research developed a National Institutes of Health-supported diversity, equity, and inclusion pathway initiative termed the "Rustbelt Investigators for the Next Generation (RING) Program" that provides research training experiences for Puerto Rican students that will help them pursue a biomedical research career in HIV. SETTING: The RING Program provides 10-week research training experiences in different disciplines of HIV/AIDS for under-represented minority undergraduate and masters students from 4 campuses (Río Piedras, Mayagüez, Humacao, and Cayey) at the University of Puerto Rico. Mentors are drawn from both CWRU and Pitt. RESULTS: The RING Program recently completed our first wave of recruitment. Recruitment sessions were either virtual or on site at the University of Puerto Rico campuses and included an overview presentation, a Q&A session, and in-person interviews. We interviewed 32 eligible applicants and accepted 10 into the program, of which 9 were female. Five students were matched with faculty at CWRU and 5 with faculty at Pitt. CONCLUSIONS: The RING Program is a comprehensive program in laboratory and implementation science that aims to enhance under-represented Hispanic undergraduate and masters students' passion for pursuing a biomedical research career in HIV.

SARS-CoV-2 Variants of Concern and Clinical Severity in the Mexican Pediatric Population.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) presents global heterogeneity, and their relative effect on pediatric severity is still limited. In this study, we associate VOCs with pediatric clinical severity outcomes in Mexico. Bioinformatics methods were used to characterize VOCs and single amino acid (aa) mutations in 75,348 SARS-CoV-2 genetic sequences from February 2020 to October 2022. High-predominance VOCs groups were calculated and subsequently associated with 372,989 COVID-19 clinical pediatric outcomes. We identified 21 high-frequency mutations related to Omicron lineages with an increased prevalence in pediatric sequences compared to adults. Alpha and the other lineages had a significant increase in case fatality rate (CFR), intensive critical unit (ICU) admission, and automated mechanical ventilation (AMV). Furthermore, a logistic model with age-adjusted variables estimated an increased risk of hospitalization, ICU/AMV, and death in Gamma and Alpha, in contrast to the other lineages. We found that, regardless of the VOCs lineage, infant patients presented the worst severity prognoses. Our findings improve the understanding of the impact of VOCs on pediatric patients across time, regions, and clinical outcomes. Enhanced understanding of the pediatric severity for VOCs would enable the development and improvement of public health strategies worldwide.

Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Anti-Inflammatory Potential of Seasonal Sonoran Propolis Extracts and Some of Their Main Constituents.

Biological properties of Sonoran propolis (SP) are influenced by harvest time. Caborca propolis showed cellular protective capacity against reactive oxygen species, which might be implicated in anti-inflammatory effects. However, the anti-inflammatory activity of SP has not been investigated so far. This study investigated the anti-inflammatory activity of previously characterized seasonal SP extracts (SPE) and some of their main constituents (SPC). The anti-inflammatory activity of SPE and SPC was evaluated by measuring nitric oxide (NO) production, protein denaturation inhibition, heat-induced hemolysis inhibition, and hypotonicity-induced hemolysis inhibition. SPE from spring, autumn, and winter showed a higher cytotoxic effect on RAW 264.7 cells (IC50: 26.6 to 30.2 µg/mL) compared with summer extract (IC50: 49.4 µg/mL). SPE from spring reduced the NO secretion to basal levels at the lowest concentration tested (5 µg/mL). SPE inhibited the protein denaturation by 79% to 100%, and autumn showed the highest inhibitory activity. SPE stabilized erythrocyte membrane against heat-induced and hypotonicity-induced hemolysis in a concentration-dependent manner. Results indicate that the flavonoids chrysin, galangin, and pinocembrin could contribute to the anti-inflammatory activity of SPE and that the harvest time influences such a property. This study presents evidence of SPE pharmacological potential and some of their constituents.