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.

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.

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)

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.

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.

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.

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.

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.

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.

[Results of abdominal wall closure using the 4:1 suture/wound lenght technique]. / Resultados del cierre de pared abdominal utilizando técnica longitud sutura/herida 4:1.

Background: Laparotomy is a daily procedure for the general surgeon and its main complication is the formation of hernias. Objective: To determine if the suture length to wound length ratio 4:1 for wall closure decreases the incidence of hernia. Material and methods: Data from patients (n = 86) in whom abdominal wall closure was performed from August 2017 to January 2018 were prospectively reviewed. Patients who could not undergo adequate follow-up, those managed with open abdomen, or those with use of non-absorbable suture materials were excluded. 2 groups were formed: in one, the suture length to wound length ratio 4:1 technique was used as wall closure, and in the other it was used conventional suture; the length of the wound-suture length was measured, and the follow-up was post-surgical. For statistical analysis it was used descriptive statistics and inferential statistics (chi-squared and Mann-Withney's U). Results: The 2 groups had similar characteristics in all the inclusion criteria. There was a statistically significant difference in dehiscence and hernias. For both complications, the 4:1 suture is a protective factor. For the first it was obtained: p = 0.000, relative risk (RR) 0.114 with 95% confidence interval (95% CI) 0.030-0.437, and for the second, p = 0.000, RR .091, 95% CI 0.027-0.437. Conclusions: Abdominal wall closure using 4:1 suture/wound length was shown to decrease the incidence of hernia.

Introducción: la laparotomía es un procedimiento cotidiano del cirujano general y una su principales complicaciones es la formación de hernias. Objetivo: determinar si la relación 4:1 longitud de sutura-largo de herida para cierre de pared disminuye la incidencia de hernia. Material y métodos: datos de pacientes (n = 86) en quienes se realizó cierre de pared abdominal de agosto de 2017 a enero de 2018 fueron revisados prospectivamente. Fueron excluidos los pacientes a quienes no se les pudo realizar el seguimiento adecuado, los manejados con abdomen abierto, o en los que se utilizaron de materiales de sutura no absorbibles. Se formaron 2 grupos: en uno se utilizó la técnica 4:1 longitud de sutura-largo de herida como cierre de pared, y en el otro la sutura convencional; se midió la longitud de herida-largo de sutura y el seguimiento fue en el postquirúrgico. Para el análisis estadístico, se usó estadística descriptiva y estadística inferencial (chi cuadrada y U de Mann-Withney). Resultados: los 2 grupos tuvieron características semejantes en todos los criterios de inclusión. Hubo diferencia estadísticamente significativa en dehiscencia y hernias; para ambas complicaciones, la sutura 4:1 es un factor protector. Para la primera se obtuvo una p = 0.000, razón de riesgo (RR) 0.114 con intervalo de confianza del 95% (IC 95%) 0.030-0.437 y en la segunda una p = 0.000, RR 0.091, IC 95% 0.027-0.437. Conclusiones: el cierre de pared abdominal con longitud sutura/herida 4:1 demostró que disminuye la incidencia de hernia.

Técnica de la incisión y cierre de piel en "punto de mira" para la reversión de estoma. Experiencia en el Centro Médico Nacional "La Raza", México / Gunsight skin incision and closure technique for stoma reversal. Experience in Centro Médico Nacional "La Raza", México

RESUMEN Antecedentes: la cirugía de restitución del tránsito intestinal presenta complicaciones posoperatorias tales como infección de sitio quirúrgico, asociado a percepción de pobre resultado cosmético por parte de los pacientes. Objetivo: describir la técnica quirúrgica de incisión y cierre de piel en "punto de mira" para la reversión de estoma y los resultados posoperatorios. Material y métodos: entre noviembre de 2020 y mayo de 2021 se realizó esta técnica a 15 pacientes con estatus de colostomía e ileostomía. Se analizaron los resultados transoperatorios y posoperatorios. Resultados: edad promedio: 38±2,5 años, índice de masa corporal: 28±1,5 kg/m2, tiempo de estadía hospitalaria: 4±2 días. La técnica presentó buena exposición de tejidos y ningún paciente presentó infección de sitio quirúrgico. A los 30 días del alta, el 100% de los pacientes expresaron alta satisfacción por el resultado estético evidenciado mediante la escala Likert 3. Conclusión: la utilización de este procedimiento ofrece ventajas técnicas, y alta satisfacción de los pacientes.

ABSTRACT Background: Stoma reversal has postoperative complications such as surgical site infection associated with patients' perception of a poor cosmetic outcome. Objective: The aim of this study is to describe the gunsight skin incision and closure technique for stoma reversal and the postoperative results. Material and methods: Between November 2020 and May 2021, this technique was performed on 15 patients with colostomy and ileostomy. The intraoperative and postoperative results were analyzed. Results: Mean age was 38 ± 2.5 years, body mass index was 28±1.5 kg/m2, and length of hospital stay was 4 ± 2 days. The technique provided good tissue exposure and no patients presented surgical site infection. Thirty days after discharge 100% of patients reported high satisfaction with the cosmetic result as evidenced by the 3-point Likert scale. Conclusion: This procedure offers technical advantages and high patient satisfaction.

Propolis: Antineoplastic Activity, Constituents, and Mechanisms of Action.

Propolis is a beehive product with great pharmacological potential, including antineoplastic activity. OBJECTIVES: The aim of this study is to provide an actual understanding of the existent scientific information regarding the antiproliferative effect of propolis, proposed mechanisms of action, and challenges to meet. METHODS: An assessment of the scientific literature was attained using the PubMed and SciFinder platforms. Research papers, clinical trials, and reviews published between the years 2000 - 2021, were considered. The words "anticancer", "antitumor", "antiproliferative" and "propolis" were used in the search criteria. CONCLUSION: A summary of several antiproliferative activities of different types of propolis is exposed. The potential health benefits of propolis are discussed. The variable plant origin of propolis partially accounts for its anti-cancer activities. Even when some mechanisms of action of propolis have been proposed, much of the genesis of how this effect is produced is yet to be answered, including several molecular mechanisms in different biological systems.