Advancing Inclusive Biodiversity Research: Strategies for Equitable Practices and Collective Impact / Promovendo a Pesquisa Inclusiva em Biodiversidade: Estratégias para Práticas Equitativas e Impacto Coletivo

Biodiversity research is essential for addressing the global biodiversity crisis, necessitating diverse participation and perspectives. However, the field currently faces a significant inclusivity problem as local expertise from biodiversity-rich but economically disadvantaged regions is often underrepresented. The underrepresentation of local experts is driven by four main challenges: linguistic bias, undervalued contributions, parachute science practices, and capacity constraints. While fragmented solutions exist, a unified multi-stakeholder approach is necessary to address these interconnected and systemic issues. Here, we introduce a holistic framework of collective responsibility, integrating tailored strategies that embrace diversity and dismantle systemic barriers for equitable collaboration. This framework delineates the diverse actors and practices required for promoting inclusivity in biodiversity research, assigning clear responsibilities to researchers, publishers, institutions, and funding bodies. Strategies for researchers include cultivating self-awareness, expanding literature searches, fostering partnerships with local experts, and promoting knowledge exchange. For institutions, we recommend establishing specialized liaison roles, implementing equitable policies, allocating resources for diversity initiatives, and enhancing support for international researchers. Publishers can facilitate multilingual dissemination, remove financial barriers, establish inclusivity standards, and ensure equitable representation in peer review. Funders should remove systemic barriers, strengthen research networks, and prioritize equitable resource allocation. Implementing these stakeholder-specific strategies can help dismantle deep-rooted biases and structural inequities in biodiversity research, catalyzing a shift towards a more inclusive and representative model that amplifies diverse perspectives and maximizes collective knowledge for effective global conservation.

A pesquisa em biodiversidade é essencial para enfrentar a crise global de biodiversidade, exigindo perspectivas diversificadas. No entanto, este campo do conhecimento enfrenta um significativo problema de inclusão, uma vez que os conhecimentos ecológicos produzidos em áreas ricas em biodiversidade, mas economicamente desfavorecidas, são frequentemente sub-representados. Esta sub-representação é impulsionada por quatro desafios principais: viés linguístico, contribuições científicas subvalorizadas, colaborações baseadas em práticas colonialistas (parachute science) e lacunas na capacitação e no acesso a dados. Embora soluções fragmentadas existam, uma abordagem multilateral unificada é necessária para abordar estas questões sistêmicas. Aqui, introduzimos uma abordagem holística de responsabilidade coletiva, integrando estratégias personalizadas que abraçam a diversidade e desmantelam barreiras sistêmicas para uma colaboração equitativa. Esta abordagem delineia os diversos atores e práticas necessárias para promover a inclusão na pesquisa sobre biodiversidade, atribuindo responsabilidades claras a pesquisadores, editoras, instituições e órgãos de fomento. As estratégias para os investigadores incluem o cultivo da autoconsciência, a expansão das pesquisas bibliográficas, o fomento de parcerias com especialistas locais e a promoção do intercâmbio de conhecimentos. Para as instituições, recomendamos o estabelecimento de funções de intermediação especializadas, a implementação de políticas equitativas, a alocação de recursos para iniciativas de diversidade e o reforço do apoio a pesquisadores internacionais. As editoras podem facilitar a divulgação multilíngue, eliminar barreiras financeiras, estabelecer normas de inclusão e assegurar uma representação equitativa na avaliação pelos pares. Os financiadores devem eliminar barreiras sistêmicas, fortalecer redes de pesquisa e dar prioridade à distribuição equitativa de recursos. A implementação dessas estratégias específicas para as partes interessadas pode ajudar a desmantelar vieses profundamente enraizados e desigualdades estruturais na pesquisa de biodiversidade, catalisando uma mudança para um modelo mais inclusivo e representativo que amplifica perspectivas diversas e maximiza o conhecimento coletivo para uma eficaz conservação da biodiversidade global.

Advancing Inclusive Biodiversity Research: Strategies for Equitable Practices and Collective Impact / Promoción de la investigación inclusiva sobre la biodiversidad: estrategias para prácticas equitativas e impacto colectivo

Biodiversity research is essential for addressing the global biodiversity crisis, necessitating diverse participation and perspectives. However, the field currently faces a significant inclusivity problem as local expertise from biodiversity-rich but economically disadvantaged regions is often underrepresented. The underrepresentation of local experts is driven by four main challenges: linguistic bias, undervalued contributions, parachute science practices, and capacity constraints. While fragmented solutions exist, a unified multi-stakeholder approach is necessary to address these interconnected and systemic issues. Here, we introduce a holistic framework of collective responsibility, integrating tailored strategies that embrace diversity and dismantle systemic barriers for equitable collaboration. This framework delineates the diverse actors and practices required for promoting inclusivity in biodiversity research, assigning clear responsibilities to researchers, publishers, institutions, and funding bodies. Strategies for researchers include cultivating self-awareness, expanding literature searches, fostering partnerships with local experts, and promoting knowledge exchange. For institutions, we recommend establishing specialized liaison roles, implementing equitable policies, allocating resources for diversity initiatives, and enhancing support for international researchers. Publishers can facilitate multilingual dissemination, remove financial barriers, establish inclusivity standards, and ensure equitable representation in peer review. Funders should remove systemic barriers, strengthen research networks, and prioritize equitable resource allocation. Implementing these stakeholder-specific strategies can help dismantle deep-rooted biases and structural inequities in biodiversity research, catalyzing a shift towards a more inclusive and representative model that amplifies diverse perspectives and maximizes collective knowledge for effective global conservation.

La investigación sobre la biodiversidad es esencial para hacer frente a la crisis mundial de la biodiversidad, lo cual requiere una participación y perspectivas diversas. Sin embargo, el estudio de la biodiversidad se enfrenta actualmente a un importante problema de inclusión, ya que los conocimientos locales de regiones altamente biodiversas, aunque económicamente desfavorecidas, suelen tener menor representación. La escasa representación de los expertos locales se debe a cuatro retos principales: el sesgo lingüístico, la subestimación de contribuciones, las prácticas científicas de paracaídas y las limitaciones de capacidad. Si bien existen soluciones fragmentadas, es necesario un enfoque unificado de múltiples partes interesadas para abordar estos problemas interconectados y sistémicos. Aquí, presentamos un marco holístico de responsabilidad colectiva, integrando estrategias personalizadas que abrazan la diversidad y desmantelan las barreras sistémicas para una colaboración equitativa. Este marco delinea los diversos actores y prácticas necesarias para promover la inclusión en la investigación sobre biodiversidad, asignando responsabilidades claras a investigadores, editores, instituciones y organismos de financiación. Las estrategias para los investigadores incluyen cultivar la autoconciencia, la ampliación de las búsquedas bibliográficas, el fomento de asociaciones con expertos locales y la promoción del intercambio de conocimientos. En el caso de las instituciones, recomendamos establecer funciones de colaboración especializadas, implementar políticas equitativas, asignar recursos para iniciativas de diversidad y mejorar el apoyo a los investigadores internacionales. Los editores pueden facilitar la difusión multilingüe, eliminar las barreras financieras, establecer normas de inclusión y garantizar una representación equitativa en la revisión por pares. Los financiadores deben eliminar las barreras sistémicas, fortalecer las redes de investigación y priorizar la asignación equitativa de recursos. La implementación de estas estrategias específicas para las partes interesadas puede ayudar a desmantelar los sesgos profundamente arraigados y las desigualdades estructurales en la investigación sobre biodiversidad, catalizando un cambio hacia un modelo más inclusivo y representativo que amplifique las diversas perspectivas y maximice el conocimiento colectivo para una conservación global efectiva.

Clinical Characteristics of Idiopathic Granulomatous Mastitis in a Hispanic Border Population: A Case Series and Literature Review.

Idiopathic granulomatous mastitis (IGM) is an autoimmune condition of the breast that is commonly encountered in women of non-white ethnicity such as Southeast Asians, Middle Easterners, and Hispanics. This condition often presents as a painful breast mass, and many patients undergo invasive diagnostic procedures or surgical excision, which can lead to disfiguring scars. Early recognition and prompt treatment with immunosuppressive medications can prevent invasive workups and management. Although previously thought to require an exclusively surgical approach, it now prompts interdisciplinary management. In this context, we present a case series of patients with IGM in a Hispanic population of South Texas.

PIGA mutations and glycosylphosphatidylinositol anchor dysregulation in polyposis-associated duodenal tumorigenesis.

The pathogenesis of duodenal tumours in the inherited tumour syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated Polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumours and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of PIGA in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyses the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. Implications: PIGA somatic mutation in duodenal tumours from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.

Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention.

BACKGROUND & AIMS: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. METHODS: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. RESULTS: Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair-deficient cancers and precancers via transcriptomics analysis. CONCLUSIONS: Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers.

Non-invasive detection of slow conduction with cardiac magnetic resonance imaging for ventricular tachycardia ablation.

AIMS: Non-invasive myocardial scar characterization with cardiac magnetic resonance (CMR) has been shown to accurately identify conduction channels and can be an important aid for ventricular tachycardia (VT) ablation. A new mapping method based on targeting deceleration zones (DZs) has become one of the most commonly used strategies for VT ablation procedures. The aim of the study was to analyse the capability of CMR to identify DZs and to find predictors of arrhythmogenicity in CMR channels. METHODS AND RESULTS: Forty-four consecutive patients with structural heart disease and VT undergoing ablation after CMR at a single centre (October 2018 to July 2021) were included (mean age, 64.8 ± 11.6 years; 95.5% male; 70.5% with ischaemic heart disease; a mean ejection fraction of 32.3 ± 7.8%). The characteristics of CMR channels were analysed, and correlations with DZs detected during isochronal late activation mapping in both baseline maps and remaps were determined. Overall, 109 automatically detected CMR channels were analysed (2.48 ± 1.15 per patient; length, 57.91 ± 63.07 mm; conducting channel mass, 2.06 ± 2.67 g; protectedness, 21.44 ± 25.39 mm). Overall, 76.1% of CMR channels were associated with a DZ. A univariate analysis showed that channels associated with DZs were longer [67.81 ± 68.45 vs. 26.31 ± 21.25 mm, odds ratio (OR) 1.03, P = 0.010], with a higher border zone (BZ) mass (2.41 ± 2.91 vs. 0.87 ± 0.86 g, OR 2.46, P = 0.011) and greater protectedness (24.97 ± 27.72 vs. 10.19 ± 9.52 mm, OR 1.08, P = 0.021). CONCLUSION: Non-invasive detection of targets for VT ablation is possible with CMR. Deceleration zones found during electroanatomical mapping accurately correlate with CMR channels, especially those with increased length, BZ mass, and protectedness.

Waist Remodeling without Incision, with Ultrasound-guided Monocortical Fracture.

Background: Rib remodeling is a surgical technique for waist shaping in women and men. However, one of the main patient complaints is the scar. We aimed to describe a scarless, ultrasound-guided rib remodeling (RibXcar) technique that assessed the degree of angular variation of the fracture by ultrasound and the variation in waist measurement and patient satisfaction through a survey. Methods: The RibXcar technique was performed in 30 women aged 18-35 years in Peru, Colombia, and Mexico between October and December 2022 by three board-certified plastic surgeons trained in ultrasound and in this technique. The plastic surgeons measured costal angles before and immediately, 1 month, and 3 months after the surgery by ultrasound, as well as the waist in the same site and at these time points. Similarly, patient satisfaction was surveyed 3 months after the surgery, in which questions were asked about body aesthetics and the puncture site. Results: Ultrasound angular measurements before and immediately, 1 month, and 3 months after the surgical procedure were 168.00, 158.00, 160.00, and 160.43 degrees in the 10th rib, 170.50, 160.50, 152.50, and 163.50 degrees in the 11th rib, and 172.00, 162.00, 154.00, and 165.00 degrees in the 12th rib, respectively. The satisfaction survey showed that patients were satisfied with the aesthetic results of both the shape of the waist and the puncture site. Conclusions: RibXcar surgery maintains the angular variation over time. Similarly, waist measurements show a sustained reduction. Three months postoperatively, the patients were satisfied with the aesthetic results of the waist and the puncture site.

Kite Mastopexy: Small Scar and Tissue-conserving Technique.

Background: Breasts are considered one of the most physically and sexually appealing features of the female body. Reduction/augmentation techniques have greatly evolved in the last decades.We are reporting our experience with an innovative technique for mastopexy that recovers the aesthetics of the breast and avoids over-resection of its lower pole. Methods: Inclusion criteria were women who underwent kite mastopexy with or without implants between January 2018 and May 2022 in a single center (Bogota, Colombia). Exclusion criteria were patients with American Society of Anesthesiology score more than II, with any uncontrolled chronic illness and/or medical history of diabetic mellitus, metabolic syndrome, body mass index more than 32 kg per m2, and active smokers. Results: We found 133 consecutive female patients. Age range was 18 and 67 years (median 39). Breast implants were used for the purpose of kite mastopexy in 52% cases. Patients were divided into two groups: implants (group 1) versus no implants (group 2). Procedure 1 involved mastopexy without implants; procedure 2 included current implant users who underwent either implant removal or in whom implants were not used for the sake of mastopexy. Procedures 3 and 4 included patients who underwent either new implant placement or implant exchange, respectively. Average time of surgery was 1.5 hours. Minor complications were mostly related to wound dehiscence. No major complications were reported. Conclusions: Kite mastopexy restores the breast aesthetics by following specific markings, a new plication of breast pillars, and a reduced scar. Our technique demonstrates a very low rate of complications while entailing natural and appealing results.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Diverse approaches to nature recovery are needed to meet the varied needs of people and nature.

Conservation and restoration projects often fail to engage local communities during the planning and implementation stage. In addition, when considering urban boundary ecosystems, there exists a wide range of stakeholders that must be involved in the planning process to ensure social equity in land management outcomes. Traditional methods for assessing future landscape change scenarios have been critiqued for their inability to adequately incorporate the diverse range of stakeholder values. This paper presents a multicriteria mapping study, incorporating a novel application of the Nature Futures Framework, to assess nature recovery scenarios on Brighton and Hove's Downland Estate-an urban boundary landscape surrounding the city of Brighton and Hove in Sussex, South East England. We focus on two key research outcomes. First, we assess the perceived performance of alternative nature recovery options across Nature Future value perspectives and between contrasting stakeholder groups. Second, by mapping stakeholder values from our multicriteria mapping study, we demonstrate that the Nature Futures Framework provides a robust framework within which to assess the diverse values stakeholders hold for land use change. We propose that utilizing the Nature Futures Framework, in combination with the multicriteria mapping interview technique, can form a valuable tool to elicit stakeholder values that may have been hidden, or underrepresented in traditional assessment methods, and to compare the perceived performance of alternative nature recovery scenarios between stakeholder groups. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-023-01337-w.

Colorectal surveillance outcomes from an institutional longitudinal cohort of lynch syndrome carriers.

Objective: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity. Design: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions. Results: On multivariate analysis, age (≥45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P<0.001). We observed a non-statistically significant trend for Hispanics having a higher and earlier cumulative incidence of adenomas compared to non-Hispanics (P=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198). Conclusion: Screening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics.

Naproxen chemoprevention induces proliferation of cytotoxic lymphocytes in Lynch Syndrome colorectal mucosa.

Background: Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients. Methods: Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled 'Naproxen Study' were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens. Results: Using data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen. Conclusions: Our findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.

Effects of Bipolar Radiofrequency on Collagen Synthesis from Patients with Brachial Ptosis.

Radiofrequency is frequently used for skin rejuvenation, localized fat elimination and cellulite treatment. It prompts the expression of thermal shock proteins that lead to dermal thickening as a result of collagen synthesis. The authors report a histological and clinical analysis of the arm subdermal changes before and after bipolar radiofrequency treatment plus liposuction to determine their benefits for arm contouring. Methods: Inclusion criteria included patients with stage 1, 2a, and 2b brachial ptosis (Duncan classification) and upper limb fat deposits who were considered candidates for third-generation ultrasound-assisted liposculpture plus radiofrequency-assisted lipolysis/skin tightening. Arm subdermal tissue samples (5 mm³) were analyzed before and after the intervention. We used 10% formaldehyde for tissue fixation and stained each sample with hematoxylin/eosin, Masson trichrome, and antibody markers against the cell cycle Ki-67 protein. Results: We analyzed a total of 12 biopsies from six patients who meet the inclusion/exclusion criteria. Histological findings with hematoxylin/eosin revealed hyperplastic and metaplastic changes with focal distribution within the papillary and reticular dermis. Masson trichrome staining showed an increase of the characteristic basophilia of thin type-I and type-III collagen fibers. In contrast, molecular analysis reported an increase in fibroblast activity mediated by the activation of the heat shock protein HSP47. Conclusion: Radiofrequency may be a great alternative to improve skin retraction in patients with mild to moderate brachial dermatochalasis through the activation of HSP47 heat shock protein and the production of type-I and type-III collagen.

Ultrastructural Characterization of Human Gingival Fibroblasts in 3D Culture.

Cell spheroids are applied in various fields of research, such as the fabrication of three-dimensional artificial tissues in vitro, disease modeling, stem cell research, regenerative therapy, and biotechnology. A preclinical 3D culture model of primary human gingival fibroblasts free of external factors and/or chemical inducers is presented herein. The ultrastructure of the spheroids was characterized to establish a cellular model for the study of periodontal tissue regeneration. The liquid overlay technique was used with agarose to generate spheroids. Fibroblasts in 2D culture and cell spheroids were characterized by immunofluorescence, and cell spheroids were characterized by optical and scanning electron microscopy, energy-dispersive X-ray spectroscopy, backscattered electrons, and Fourier transform infrared spectroscopy. Ostegenic related genes were analyzed by RT-qPCR. Gingival fibroblasts formed spheroids spontaneously and showed amorphous calcium phosphate nanoparticle deposits on their surface. The results suggest that human gingival fibroblasts have an intrinsic potential to generate a mineralized niche in 3D culture.

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer.

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

Effect of Different Extraction Methods and Geographical Origins on the Total Phenolic Yield, Composition, and Antimicrobial Activity of Sugarcane Bagasse Extracts.

Several parameters, including particle size, solvent, temperature, and extraction method, affect phenolic compounds' extraction yield from a plant matrix. Considering the wide availability of sugarcane bagasse (SCB), this study analyzed the effect of different extraction methods and geographical origins on the yield, quality, and antimicrobial activity of phenolic compounds from SCB extracts. Samples from three geographical locations (Veracruz, Mexico; Santa Rosa, Texas, USA; and St. Mary, Louisiana, USA) were analyzed. Extraction was performed using an orbital shaker or ultrasonic bath at various times at a fixed temperature of 50°C, with 90% ethanol or methanol. The highest yield (5.91 mg GAE) was obtained using an orbital shaker for 24 h with 90% methanol as the solvent. HPLC-MS identified desferrioxamine b, baicalein, madecassic acid, and podototarin at different concentrations in all three SCB samples. The antimicrobial activity of these compounds was tested against Escherichia coli K12, Bacillus cereus, Enterobacter aerogenes, Streptococcus aureus, and Enterobacter cloacae. The antimicrobial activity was also tested against modifications of the Saccharomyces cerevisiae: the MutL Homolog 1 (MLH1), Slow Growth Suppressor (SGS1), O-6-MethylGuanine-DNA methyltransferase (MGT1), and RADiation sensitive (RAD14), carrying mutations related to different cancer types. In addition, the results were compared with the effect of ampicillin and kanamycin. The SCB extracts showed up to 90% growth inhibition against B. cereus at 200-800 µg/mL and 50% growth inhibition against S. aureus at 800 µg/mL. The inhibitory effect against modified yeast SGS1, RAD14, and MLH1 was 50-80% at 800 µg/mL. The percentage of inhibition and the phenolic compound contents differed depending on the origin of the SCB sample. These findings are promising for using this industrial byproduct to obtain compounds for nutraceutical, food additive, or medical uses.

Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability.

Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the intoxication is mainly focused on treating the symptoms, meaning there is no specific antidote against VTD. In this pursuit, we were interested in studying the molecular interactions of VTD with cyclodextrins (CDs). CDs are supramolecular macrocycles with the ability to form host-guest inclusion complexes (ICs) inside their hydrophobic cavity. Since VTD is a lipid-soluble alkaloid, we hypothesized that it could form stable inclusion complexes with different types of CDs, resulting in changes to its physicochemical properties. In this investigation, we studied the interaction of VTD with ß-CD, γ-CD and sulfobutyl ether ß-CD (SBCD) by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. Docking and molecular dynamics studies confirmed the most stable configuration for the inclusion complexes. Finally, with an interest in understanding the effects of the VTD/CD molecular interactions, we performed cell-based assays (CBAs) on Neuro-2a cells. Our findings reveal that the use of different amounts of CDs has an antidote-like concentration-dependent effect on the cells, significantly increasing cell viability and thus opening opportunities for novel research on applications of CDs and VTD.