Hiatal Hernia of Stomach and Lesser Omentum in a Cadaver: Is It a Type III or IV?

Hiatal hernias, protrusions of abdominal viscera through the esophageal hiatus, are classified into four types. Types I and II involve ascent of the stomach without affecting the gastroesophageal junction. Types III and IV involve the gastroesophageal junction. Type IV specifically may have stomach as well as other abdominal organ involvement, such as pancreas or omentum. Among these types, type IV is the most complex and rare form, accounting for only 0.1% of all cases of hiatal hernias. This report presents a case of a type IV hiatal hernia involving the lesser omentum and a significant portion of the stomach in an 86-year-old male cadaver with a history of mediastinal surgery. To our knowledge, this presentation in a cadaver has not previously been reported in the literature.  This case highlights classification inconsistencies in the literature, particularly regarding type IV hiatal hernias. It is unclear given the current classification system, whether this presentation would be considered a type III or type IV hiatal hernia as it fits both criteria and there are several interpretations of the criteria of a type IV hiatal hernia. Inconsistencies in the classification system may impede standardization of care. This report highlights the need for a more precise classification system that better accounts for anatomical changes and clinical presentation.

Prevalence of Drug-Resistant Tuberculosis in HIV-Positive and Diabetic Patients in Sinaloa, Mexico: A Retrospective Cross-Sectional Study.

Tuberculosis (TB) is a disease caused by the bacillus Mycobacterium tuberculosis (MTB). Human immunodeficiency virus (HIV) infection and type 2 diabetes mellitus (T2DM) are among the main risk factors for the development of TB and increase the risk of drug-resistant TB developing (DR-TB). The aim of this study was to estimate the prevalence of DR-TB in patients with HIV or T2DM in Sinaloa, Mexico. This was an observational and cross-sectional study. The analysis was conducted using the clinical data of patients registered on the National Epidemiological Surveillance System for TB (SINAVE/PUI-TB) platform with a presumed diagnosis of TB during 2019 to 2021 in Sinaloa, Mexico. The prevalence of DR-TB was estimated in HIV and T2DM patients, as well as the odds ratios for their sociodemographic variables, using the Chi-square test. There were 2, 4, and 4 TB-HIV cases and 2, 6, and 9 TB-T2DM cases during 2019, 2020, and 2021, respectively, whereas there were 2 and 1 DRTB-HIV and DRTB-T2DM cases, respectively. The results indicated that the WHO guidelines for DR-TB were not properly applied to this high-risk population. Hence, the appropriate application of guidelines for TB and DR-TB detection in these patients needs to be immediately implemented by the State health system.

Selective Bias Virtual Screening for Discovery of Promising Antimalarial Candidates targeting Plasmodium N-Myristoyltransferase.

Malaria remains a significant public health challenge, with Plasmodium vivax being the species responsible for the most prevalent form of the disease. Given the limited therapeutic options available, the search for new antimalarials against P. vivax is urgent. This study aims to identify new inhibitors for P. vivax N-myristoyltransferase (PvNMT), an essential drug target against malaria. Through a validated virtual screening campaign, we prioritized 23 candidates for further testing. In the yeast NMT system, seven compounds exhibit a potential inhibitor phenotype. In vitro antimalarial phenotypic assays confirmed the activity of four candidates while demonstrating an absence of cytotoxicity. Enzymatic assays reveal LabMol-394 as the most promising inhibitor, displaying selectivity against the parasite and a strong correlation within the yeast system. Furthermore, molecular dynamics simulations shed some light into its binding mode. This study constitutes a substantial contribution to the exploration of a selective quinoline scaffold and provides valuable insights into the development of new antimalarial candidates.

l-carnitine enhances the kinematics and protects the sperm membranes of chilled and frozen-thawed Peruvian Paso horse spermatozoa.

l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through ß-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1-10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa.

Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1.2 to 2.3 µM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-activity relationship (QSAR) models to analyze protein-ligand interactions, revealing that these naphthoquinones exhibit a protein binding pattern similar to brequinar, a potent HsDHODH inhibitor. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.

The clinical manifestations of hyperostosis frontalis Interna: A qualitative systematic review of cases.

Hyperostosis frontalis interna (HFI) is a condition defined as abnormal bone growth on the posterior aspect of the frontal bone. Despite uncertainties regarding its etiology and prognosis, clinicians typically consider HFI a benign pathology. There are no studies organizing all the possible manifestations of the disease. The present study aims to organize all the clinical manifestations of HFI within the current case report/series literature. A blinded PRISMA-guided search of HFI case reports and case series yielded 43 relevant articles and provided 110 patients for analysis. The symptoms presenting alongside HFI were extracted and tabulated. We found high-frequency clinical manifestations of HFI (>20% of patients) to include headaches, obesity, vertigo/dizziness symptoms, cognitive decline, and depression. An additional 15 symptoms were tabulated at frequencies found to be less than 20%. Based on our analysis, we suggest the constellation of high-frequency symptoms can offer a more comprehensive clinical picture of symptomatic HFI which may be valuable to consider for clinicians and future researchers in the field of HFI.

Sequencing and description of the genome of a strain of Stenotrophomonas geniculata isolated from a patient infected with COVID-19 at Hospital Regional No.1 de Charo, Michoacán, México.

Stenotrophomonas is a bacterial genus that can be found in various environments, such as water, soil, and clinical samples. Due to their high genetic and phenotypic diversity, it is difficult to properly identify and classify all isolates. The COVID-19 pandemic caused an increase in nosocomial infections, which played a major role in the high mortality rate among patients in intensive care. This is the first report of the identification of S. geniculata as a nosocomial opportunistic pathogen isolated from a patient with COVID-19. Their genome was isolated, sequenced, and assembled, and it consists of 4,488,090 bp in 24 contigs, 4,103 coding sequences, and a G+C content of 66.58%.

Barcode-style lateral flow immunochromatographic strip for the semi-quantitative detection of ochratoxin A in coffee samples.

Ochratoxin A (OTA) is a mycotoxin contaminating agricultural products produced by fungi, associated with important toxic effects. Thus, the development of fast, sensitive, and economical approaches for OTA detection is crucial. In this study, a barcode-style lateral flow assay for the semi-quantitative detection of OTA in coffee samples was developed. To achieve this goal, a BSA-OTA complex was immobilized in three test zones to compete with OTA molecules in the sample for binding with anti-OTA antibodies labeled with gold nanoparticles. Different concentrations of OTA in the sample produced distinct colour patterns, allowing semi-quantification of the analyte. The assay exhibited high sensitivity, with a limit of detection of 2.5 µg.L-1, and high reproducibility, with variation coefficient values between 2% and 13%. Moreover, the colour patterns obtained in the analysis with coffee samples were similar to the results obtained with standard OTA solutions, demonstrating a reliable applicability in real samples.

Time warping between main epidemic time series in epidemiological surveillance.

The most common reported epidemic time series in epidemiological surveillance are the daily or weekly incidence of new cases, the hospital admission count, the ICU admission count, and the death toll, which played such a prominent role in the struggle to monitor the Covid-19 pandemic. We show that pairs of such curves are related to each other by a generalized renewal equation depending on a smooth time varying delay and a smooth ratio generalizing the reproduction number. Such a functional relation is also explored for pairs of simultaneous curves measuring the same indicator in two neighboring countries. Given two such simultaneous time series, we develop, based on a signal processing approach, an efficient numerical method for computing their time varying delay and ratio curves, and we verify that its results are consistent. Indeed, they experimentally verify symmetry and transitivity requirements and we also show, using realistic simulated data, that the method faithfully recovers time delays and ratios. We discuss several real examples where the method seems to display interpretable time delays and ratios. The proposed method generalizes and unifies many recent related attempts to take advantage of the plurality of these health data across regions or countries and time, providing a better understanding of the relationship between them. An implementation of the method is publicly available at the EpiInvert CRAN package.

Cuando negocian los rebeldes colombianos: indicadores estratégicos del acuerdo de paz con las FARC

¿Porque grupos como las FARC firmaron un acuerdo de paz, mientras otros grupos como el ELN se niegan a hacerlo? La respuesta a este interrogante está ligada al concepto de punto de inflexión, que es el momento crucial en el que los acontecimientos giran hacia su resultado final. National Security Research Division (RAND) ha determinado indicadores comunes a los puntos de inflexión de ochenta y nueve conflictos contrainsurgentes, con el fin de promover e identificar la llegada de esta fase final del conflicto. Este trabajo presenta una metodología de análisis cualitativo basada en estos indicadores de debilitamiento de la insurgencia, que sugieren los posibles resultados de los conflictos contrainsurgentes. Estos indicadores se relacionan con la dinámica del conflicto colombiano, lo que permite validar determinadas condiciones estratégicas que posibilitaron la salida negociada al conflicto con las FARC (Fuerzas Armadas Revolucionarias de Colombia). Las conclusiones incluyen ocho indicadores presentes en el curso del conflicto sin los cuales no hubiese sido posible el acuerdo de paz en el resultado tipo II: Gobierno Gana. El estudio propone criterios de evaluación y gestión del conflicto.

Why did groups like FARC sign a peace agreement while other groups like ELN refuse to do so? The answer to this question is linked to the concept of a tipping point, which is the point at which events take a crucial turn toward their outcome. The National Security Research Division (RAND) determined strategic indicators common to tipping points in 89 counterinsurgency conflicts to promote and identify the arrival of this final phase of the conflict. This work presents a qualitative analysis methodology based on these indicators of insurgency weakening that suggest possible outcomes of counterinsurgency conflicts. These indicators are related to information on the dynamics of the Colombian conflict, which allows validation of certain strategic conditions that enabled the negotiated exit from the conflict with FARC. The conclusions include eight indicators present in the course of the conflict without which the peace agreement would not have been possible in the Type II outcome: Government Wins. The study proposes criteria for conflict evaluation and management.

Por que grupos como as FARC assinaram um acordo de paz, enquanto outros grupos, como o ELN, se recusaram a fazê-lo? A resposta a essa pergunta está ligada ao conceito de ponto de inflexão, que é o momento crucial em que os eventos se voltam para seu resultado final. A National Security Research Division (RAND) identificou indicadores comuns aos pontos de inflexão de 89 conflitos de contrainsurgência para promover e identificar a chegada dessa fase final do conflito. Este documento apresenta uma metodologia de análise qualitativa com base nesses indicadores de enfraquecimento da insurgência, que sugerem os possíveis resultados dos conflitos de contrainsurgência. Esses indicadores estão relacionados à dinâmica do conflito colombiano, o que permite a validação de determinadas condições estratégicas que possibilitaram a solução negociada do conflito com as FARC (Forças Armadas Revolucionárias da Colômbia). As conclusões incluem oito indicadores presentes no curso do conflito, sem os quais o acordo de paz não teria sido possível no resultado do tipo II: vitórias do governo. O estudo propõe critérios para avaliação e gerenciamento de conflitos.

Calidad de atención interhospitalaria: Revisión sistemática / Quality of interhospital care: Systematic review / Qualidade do atendimento inter-hospitalar: revisão sistemática

En la actualidad la calidad de atención durante los traslados interhospitalarios de pacientes es una tarea compleja, que desafía la capacidad del personal de salud para mantener un ambiente de cuidado alrededor de estos pacientes. Objetivo. Analizar la calidad de atención interhospitalaria. Metodología. Se realizó una revisión sistemática y se evalúa la calidad de atención interhospitalaria. En la búsqueda de información se utilizaron términos DeCS y operadores boleanos con algoritmos (calidad de atención) AND (Interhospitalaria); (Care quality) AND (Interhospital). Considerando estudios de 2017-2023, en bases de datos como PubMed se obtuvieron 48 artículos, PLoS one 5 artículos, Science Direct 11, Scielo 33 artículos, Sage Journals 6, Elsevier 7, Springer Link 5 artículos. De los 131 artículos en total, se eliminaron 70 en base a resúmenes incompletos y se excluyeron 34 artículos que no tenían información completa; obteniendo 17 artículos para realizar la extracción y el análisis de los datos. Conclusión. Existen estrategias para una adecuada atención interhospitalaria, tales como: oxigenación por membrana extracorpórea como una opción para transportar de forma segura a los pacientes con Síndrome de distrés respiratorio agudo grave, es fundamental garantizar medidas de higiene y el suministro de equipos de protección personal para prevenir propagación de enfermedades; asegurar adecuada comunicación e intercambio de información, a través de medios virtuales, tanto para los familiares y personal; es esencial tener un plan general para prevenir cualquier evento impredecible y agudo, mejoran la eficiencia de la prestación de atención médica, lo que finalmente se traduce en mejores resultados para los pacientes.

Currently, the quality of care during interhospital transfers of patients is a complex task, which challenges the ability of health care personnel to maintain a caring environment around these patients. Objective. To analyze the quality of interhospital care. Methodology. A systematic review was carried out and the quality of interhospital care was evaluated. DeCS terms and Boolean operators with algorithms (Care quality) AND (Interhospital); (Care quality) AND (Interhospital) were used in the information search. Considering studies from 2017-2023, in databases such as PubMed 48 articles were obtained, PLoS one 5 articles, Science Direct 11, Scielo 33 articles, Sage Journals 6, Elsevier 7, Springer Link 5 articles. Of the 131 articles in total, 70 were eliminated based on incomplete abstracts and 34 articles that did not have complete information were excluded; obtaining 17 articles to perform data extraction and analysis. Conclusion. There are strategies for adequate interhospital care, such as: extracorporeal membrane oxygenation as an option to safely transport patients with Severe Acute Respiratory Distress Syndrome, it is essential to ensure hygiene measures and the provision of personal protective equipment to prevent the spread of disease; ensure adequate communication and exchange of information, through virtual means, both for family members and staff; it is essential to have a general plan to prevent any unpredictable and acute event, improve the efficiency of health care delivery, which ultimately translates into better outcomes for patients.

A qualidade do atendimento durante as transferências inter-hospitalares de pacientes é atualmente uma tarefa complexa, que desafia a capacidade da equipe de saúde de manter um ambiente de cuidado em torno desses pacientes. Objetivo. Analisar a qualidade do atendimento interhospitalar. Metodologia. Realizamos uma revisão sistemática e avaliamos a qualidade do atendimento inter-hospitalar. Na busca de informações, foram utilizados termos do DeCS e operadores booleanos com algoritmos (Care quality) AND (Interhospital); (Care quality) AND (Interhospital). Considerando estudos de 2017 a 2023, foram obtidos 48 artigos em bancos de dados como PubMed, 5 artigos em PLoS one, 11 artigos em Science Direct, 33 artigos em Scielo, 6 artigos em Sage Journals, 7 artigos em Elsevier e 5 artigos em Springer Link. Do total de 131 artigos, 70 artigos foram eliminados com base em resumos incompletos e 34 artigos foram excluídos por não terem informações completas, obtendo-se 17 artigos para extração e análise de dados. Conclusões. Existem estratégias para o atendimento inter-hospitalar adequado, tais como oxigenação por membrana extracorpórea como uma opção para o transporte seguro de pacientes com síndrome da angústia respiratória aguda grave; garantia de medidas de higiene e fornecimento de equipamentos de proteção individual para evitar a propagação de doenças; garantia de comunicação e troca de informações adequadas, por meios virtuais, tanto para os familiares quanto para a equipe; ter um plano geral para evitar qualquer evento imprevisível e agudo é essencial para melhorar a eficiência da prestação de serviços de saúde, o que, em última análise, se traduz em melhores resultados para os pacientes.

Genomic Profiling of Multidrug-Resistant Swine Escherichia coli and Clonal Relationship to Human Isolates in Peru.

The misuse of antibiotics is accelerating antimicrobial resistance (AMR) in Escherichia coli isolated from farm animals. The genomes of ten multidrug-resistant (MDR) E. coli isolates from pigs were analyzed to determine their sequence types, serotypes, virulence, and AMR genes (ARGs). Additionally, the relationship was evaluated adding all the available genomes of Peruvian E. coli from humans using the cgMLST + HierCC scheme. Two aEPEC O186:H11-ST29 were identified, of which H11 and ST29 are reported in aEPEC isolates from different sources. An isolate ETEC-O149:H10-ST100 was identified, considered a high-risk clone that is frequently reported in different countries as a cause of diarrhea in piglets. One ExPEC O101:H11-ST167 was identified, for which ST167 is an international high-risk clone related to urinary infections in humans. We identified many ARGs, including extended-spectrum ß-lactamase genes, and one ETEC harboring the mcr-1 gene. CgMLST + HierCC analysis differentiated three clusters, and in two, the human isolates were grouped with those of swine in the same cluster. We observed that Peruvian swine MDR E. coli cluster with Peruvian E. coli isolates from healthy humans and from clinical cases, which is of great public health concern and evidence that AMR surveillance should be strengthened based on the One Health approach.

Winds of change a tale of: asthma and microbiome.

The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.

On a generalized Klausmeier model.

In this paper we study a generalized Klausmeier model replacing the integer derivative by a local fractional derivative. This derivative enables us to consider a wide range of systems with already well-known derivatives. We analyze the stability of this new model as well as the homotopic perturbation method. Finally, an inverse problem associated with a real data set is solved.

Triclabendazole resistance in Fasciola hepatica: First report in sheep from the Santa Cruz province, Argentinian Patagonia.

In the fall of 2022, decreased triclabendazole (TCBZ) efficacy against F. hepatica was suspected in a sheep farm located in the Santa Cruz province, Argentinian Patagonia. Since TCBZ-resistance in F. hepatica has never been reported in this province, this study aimed to confirm potential TCBZ-resistance in F. hepatica and to evaluate the efficacy of closantel (CLO) and nitroxinil (NTX), through faecal egg count reduction test (FECRT), and the efficacy of albendazole (ABZ) through the in vitro egg hatch test (EHT) in sheep. Sixty-eight (68) animals were selected from a herd of eighty (80) female Merino naturally infected with F. hepatica based on eggs per gram of F. hepatica (EPGFh) counts and assigned into four (4) groups (n = 17 per group): Group Control, animals did not receive anthelmintic treatment; Group TCBZ, animals were orally treated with TCBZ (12 mg/kg); Group CLO, animals were orally treated with CLO (10 mg/kg); and Group NTX, animals were subcutaneously treated with NTX (10 mg/kg). The fluke egg output was monitored on days 0 and 21 post-treatment. For the EHT, liver fluke eggs were isolated from faecal samples (approx. 50 g) collected from animals of the control group. TCBZ efficacy against liver fluke was 53.4%, confirming the presence of TCBZ-resistant isolates on the farm. CLO and NTX were highly effective (100%) for the treatment of F. hepatica on this farm. The EHT was carried out in two different laboratories, in which was observed an ABZ efficacy of 95.8 (Bariloche) and 96.5% (Tandil). These results indicate the ABZ susceptibility of this F. hepatica isolate and the inter-laboratory precision of the test.

Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity.

Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic compounds with novel mechanisms of action. The success of kinase inhibitors for oncological treatments has paved the way for the exploitation of protein kinases as drug targets in various diseases, including malaria. Casein kinases are ubiquitous serine/threonine kinases involved in a wide range of cellular processes such as mitotic checkpoint signaling, DNA damage response, and circadian rhythm. In Plasmodium, it is suggested that these protein kinases are essential for both asexual and sexual blood-stage parasites, reinforcing their potential as targets for multi-stage antimalarials. To identify new putative PfCK2α inhibitors, we utilized an in silico chemogenomic strategy involving virtual screening with docking simulations and quantitative structure-activity relationship predictions. Our investigation resulted in the discovery of a new quinazoline molecule (542), which exhibited potent activity against asexual blood stages and a high selectivity index (>100). Subsequently, we conducted chemical-genetic interaction analysis on yeasts with mutations in casein kinases. Our chemical-genetic interaction results are consistent with the hypothesis that 542 inhibits yeast Cka1, which has a hinge region with high similarity to PfCK2α. This finding is in agreement with our in silico results suggesting that 542 inhibits PfCK2α via hinge region interaction.

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity.

In tropical and subtropical areas, malaria stands as a profound public health challenge, causing an estimated 247 million cases worldwide annually. Given the absence of a viable vaccine, the timely and effective treatment of malaria remains a critical priority. However, the growing resistance of parasites to currently utilized drugs underscores the critical need for the identification of new antimalarial therapies. Here, we aimed to identify potential new drug candidates against Plasmodium falciparum, the main causative agent of malaria, by analyzing the transcriptomes of different life stages of the parasite and identifying highly expressed genes. We searched for genes that were expressed in all stages of the parasite's life cycle, including the asexual blood stage, gametocyte stage, liver stage, and sexual stages in the insect vector, using transcriptomics data from publicly available databases. From this analysis, we found 674 overlapping genes, including 409 essential ones. By searching through drug target databases, we discovered 70 potential drug targets and 75 associated bioactive compounds. We sought to expand this analysis to similar compounds to known drugs. So, we found a list of 1557 similar compounds, which we predicted as actives and inactives using previously developed machine learning models against five life stages of Plasmodium spp. From this analysis, two compounds were selected, and the reactions were experimentally evaluated. The compounds HSP-990 and silvestrol aglycone showed potent inhibitory activity at nanomolar concentrations against the P. falciparum 3D7 strain asexual blood stage. Moreover, silvestrol aglycone exhibited low cytotoxicity in mammalian cells, transmission-blocking potential, and inhibitory activity comparable to those of established antimalarials. These findings warrant further investigation of silvestrol aglycone as a potential dual-acting antimalarial and transmission-blocking candidate for malaria control.

An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration.

During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 µg/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.