A Novel Minimally Invasive Surgically Induced Skeletal Muscle Injury Model in Sheep.

Sports-related muscle injuries account for 10-55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.

Epidemiological and clinical description of patients with oropharyngeal cancer treated in a public oncology referral hospital in Chile.

Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile.

Autonomous Robotic Surgery: Has the Future Arrived?

Autonomous robotic surgery represents a pioneering field dedicated to the integration of robotic systems with varying degrees of autonomy for the execution of surgical procedures. This paradigm shift is made possible by the progressive integration of artificial intelligence (AI) and machine learning (ML) into the realm of surgical interventions. While the majority of autonomous robotic systems remain in the experimental phase, a notable subset has successfully transitioned into clinical applications. Noteworthy procedures, such as venipuncture, hair implantations, intestinal anastomosis, total knee replacement, cochlear implant, radiosurgery, and knot tying, among others, exemplify the current capabilities of autonomous surgical systems. This review endeavors to comprehensively address facets of autonomous robotic surgery, commencing with a concise elucidation of fundamental concepts and traversing the pivotal milestones in the historical evolution of robotic surgery. This historical trajectory underscores the incremental assimilation of autonomous systems into surgical practices. This review aims to address topics related to autonomous robotic surgery, starting with a description of fundamental concepts and going through the milestones in robotic surgery history that also show the gradual incorporations of autonomous systems. It also includes a discussion of the key benefits and risks of this technology, the degrees of autonomy in surgical robots, their limitations, the current legal regulations governing their usage, and the main ethical concerns inherent to their nature.

Viewpoint on Human Immunodeficiency Virus Medical Care Retention Guidelines in the Coronavirus 2019 Pandemic Era and Beyond: Lessons Learned From Electronic Health Record Screening and Outreach.

In this viewpoint, we discuss retention in care for people with human immunodeficiency virus (HIV) and call into question the methodology used to characterize retention, as well as the definitions themselves. Optimal retention for people with HIV (PWH) is defined in multiple ways by major healthcare leaders in the United States, typically focusing on appointment attendance or laboratory work. Yet, these definitions rely on in-person encounters, an approach to care that is becoming less common due to the rise of telehealth visits, particularly in light of the coronavirus disease 2019 pandemic. Our recent work showed that relying on electronic health records to identify PWH who were not retained in care not only failed to capture the nuances of modern HIV medical treatment engagement, but also led to misidentification of patients' retention status due to limitations in the record system. As such, we recommend a reevaluation of how HIV medical care retention is defined and reported.

On the way to potential antifungal compounds: synthesis and in vitro activity of 2-benzofuranylacetic acid amides.

Crop losses caused by microbial infections are a significant global issue, especially in tropical regions. The development of novel antimicrobial agents, particularly antifungal agents, has been explored from various perspectives, including chemical synthesis. However, conventional approaches typically involve synthesizing new and potent compounds on a small scale (a few milligrams), making the scale-up of the reaction a major challenge. In this manuscript, we present a method for the synthesis of new and active (against Fusarium oxysporum) benzofuranyl acetic acid amides. Our strategy allows us to synthesize the key precursor on the gram scale, enabling the production of sufficient quantities of other active compounds within short timeframes for conducting biological studies. All the reactions used in this manuscript are recognized by their industrial application.

Anti-Inflammatory Effect of Izalpinin Derived from Chromolaena leivensis: λ-Carrageenan-Induced Paw Edema and In Silico Model.

The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand-protein complexes present acceptable stability, with RMSD values within the allowed range.

Enhancing distress tolerance to uplift motivation in recovery: Results from an open development trial.

Objective: This open pilot study examines the feasibility, acceptability, and qualitative outcomes of an interactive web- and text message-delivered personalized feedback intervention aimed at cultivating motivation and tolerance of distress for adults initiating outpatient buprenorphine treatment. Methods: Patients (n = 10) initiating buprenorphine within the past 8 weeks first completed a web-based intervention focused on enhancing motivation and providing psychoeducation on distress tolerance skills. Participants then received 8 weeks of daily personalized text messages that provided reminders of salient motivational factors and recommended distress tolerance-oriented coping skills. Participants completed self-report measures to assess intervention satisfaction, perceived usability, and preliminary efficacy. Additional perspectives were captured via qualitative exit interviews. Results: In total, 100% of retained participants (n = 9) engaged with the text messages throughout the entire 8-week period. Mean scores of 27 (SD = 5.05) on the Client Satisfaction Questionnaire at the end of 8-week period indicated a high degree of satisfaction with the text-based intervention. The average rating on the System Usability Scale was 65.3 at the end of the 8-week program, suggesting that the intervention was relatively easy to use. Participants also endorsed positive experiences with the intervention during qualitative interviews. Clinical improvements were observed across the intervention period. Conclusions: Preliminary findings from this pilot suggest that the content and delivery method of this combined web- and text message-based personalized feedback intervention is perceived by patients as feasible and acceptable. Leveraging digital health platforms to augment buprenorphine has potential for high scalability and impact to reduce opioid use, increase adherence/retention to treatment, and prevent future incidence of overdose. Future work will evaluate the efficacy of the intervention in a randomized clinical trial design.

Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against Fusarium oxysporum: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect.

In this manuscript, the synthesis of enamine-type Schiff bases 1−48 derived from the amino acids L-Ala, L-Tyr, and L-Phe was carried out. Their in vitro activity and in vivo protective effect against Fusarium oxysporum were also evaluated through mycelial growth inhibition and disease severity reduction under greenhouse conditions. The in vitro activity of test compounds 1−48 showed half-maximal inhibitory concentrations (IC50) at different levels below the 40 mM range. Deep analysis of the IC50 variations indicated that the size of the substituent on the acetylacetone derivatives and the electronic character on the cyclohexane-3-one fragment influenced the antifungal effect. 3D-QSAR models based on atoms (atom-based approach) were built to establish the structure−activity relationship of the test Schiff bases, showing a good correlation and predictive consistency (R2 > 0.70 and Q2 > 0.60). The respective contour analysis also provided information about the structural requirements for potentiating their antifungal activity. In particular, the amino acid-related fragment and the alkyl ester residue can favor hydrophobic interactions. In contrast, the nitrogen atoms and enamine substituent are favorable regions as H-donating and electron-withdrawing moieties. The most active compounds (40 and 41) protected cape gooseberry plants against F. oxysporum infection (disease severity index < 2), involving adequate physiological parameters (stomatal conductance > 150 mmol/m2s) after 45 days of inoculation. These promising results will allow the design of novel Schiff base-inspired antifungals using 2-amino acids as precursors.

Síntesis y actividad antifúngica in vitro frente a Fusarium oxysporum de amidas N-alquilsustituidas derivadas de 2-aminoácidos

Una serie de amidas N-alquilsustituidas 1-16 fueron sintetizadas a partir de malonato de dietilo y ésteres de alquilo derivados de los aminoácidos L-triptófano, L-alanina, L-fenilalanina y L-tirosina. Los métodos de síntesis empleados involucraron calentamiento por irradiación de microondas empleando tanto un ácido de Lewis (AlCl3) o 4-dimetilaminopiridina (DMAP) como catalizador y auxiliar nucleofílico, respectivamente. Los resultados sugieren que el uso de irradiación de microondas y de DMAP conlleva mejores rendimientos en un tiempo de reacción más corto. Para ilustrar las diferencias observadas, se presentan las propuestas mecanísticas de cada método de reacción para la formación de amidas N-alquilsustituidas. Finalmente, las amidas sintetizadas se evaluaron en condiciones in vitro frente a Fusarium oxysporum; mostraron actividad antifúngica a diferentes niveles (0,40 mM < IC50 < 29,1 mM), lo cual indicó que las variaciones de la actividad observada de este grupo de compuestos pueden deberse al efecto de la amida acíclica como bioisóstero no clásico de algunas fitoalexinas heterocíclicas.

N-alkyl substituted amides 1-16 were synthesized from diethyl malonate and alkyl esters derived from the amino acids L -tryptophan, L -alanine, L -phenylalanine, and L -tyrosine. In addition, a microwave-assisted protocol was employed using a Lewis acid (AlCl3) or dimethylaminopyridine (DMAP) as a catalyst and nucleophilic auxiliary, respectively, affording the desired compounds. The results suggest that DMAP-catalyzed reactions under microwave irradiation yield higher during short reaction times. Each reaction method's mechanistic proposals for forming N-alkyl-substituted amides are presented to illustrate the observed differences. The synthesized amides were evaluated under in vitro conditions against Fusarium oxysporum. The compounds exhibited antifungal activity at different levels (0.40 mM < IC50 < 29.1 mM). These results indicated that the observed activity variations of this compound group might be due to the effect of acyclic amide as a non-classical bioisostere of some heterocyclic phytoalexins.

Uma série de amidas N-alquil substituídas foram sintetizadas a partir de malonato de dietila e ésteres alquílicos derivados dos aminoácidos ʟ-triptofano, L -alanina, L-fenilalanina e L-tirosina. Os métodos de síntese empregados foram realizados usando aquecimento por irradiação de micro-ondas empregando um ácido de Lewis (AlCl3) ou dimetilaminopiridina (DMAP) como catalisador. Os resultados sugerem que a irradiação de micro-ondas usando DMAP leva a melhores rendimentos em um tempo de reação mais curto. Para ilustrar as diferenças observadas, são apresentadas as propostas mecanísticas de cada método de reação para a formação de amidas N-alquilsubstituídas. Finalmente, as amidas sintetizadas foram avaliadas in vitro contra Fusarium oxysporum, mostrando atividade antifúngica em diferentes níveis (0.40 mM < IC50 < 29.1 mM), o que indica que as variações observadas na atividade desse grupo de compostos podem ser devidas ao efeito de amida acíclica como um bioisóstero não clássico de algumas fitoalexinas heterocíclicas.

Perceptions of medications, program settings, and drug use histories among individuals engaged in treatment for opioid use disorder.

Background: Nearly two million adults in the US currently live with an Opioid Use Disorder (OUD) diagnosis. Recent efforts have encouraged and facilitated widespread adoption of empirically supported medications for opioid use disorder (MOUD), yet MOUD and OUD behavioral health interventions remain dramatically underutilized. Fear of discrimination and judgment, compounded by systemic and regulatory barriers, hinder individuals' access to specialty treatment.Objectives: The goal of the current study was to (1) reveal how perspectives toward OUD treatment may differ across medication types, program settings, and drug use history; (2) address systemic and regulatory components that potentially foster and propagate positive or negative attributions to OUD; and (3) understand how experiences reduce patients' willingness to pursue and/or maintain long term treatment.Methods: Twenty-four adults engaged in buprenorphine treatment at two outpatient addiction treatment centers participated in in-depth, qualitative interviews between 2019 and 2020 in Providence, Rhode Island.Results: Thematic analysis revealed negative attributions toward OUD across all participants. Three key themes developed from the coding and analysis: (1) differential perceptions of therapeutic medications (2) negative perceptions of treatment programs and (3) perceptions of drugs and people who use drugs.Conclusions: Stigmatizing language remains a major public health issue that needs to be addressed to facilitate treatment for individuals for OUD and other drug use disorders. Incorporating strategies targeting labeling across medication types, program settings, and drug use may improve treatment outcomes by reducing the inaccurate beliefs surrounding OUD and connecting patients to evidence-based support.

Feasibility and Acceptability of a Digital Health Intervention to Promote Continued Engagement in Medication for Opioid Use Disorder Following Release From Jail/Prison.

Background: Despite the extensive benefits of implementing Medications for Opioid Use Disorder (MOUD) in jail/prison, criminal justice-involved populations face significant challenges when transitioning back to the community following a period of incarceration. These risk factors are associated with increased drug use and discontinuation of evidence-based care. Novel intervention strategies are needed to support this high-risk period of transition. The primary objective of this protocol was to gather perspectives from the target population to optimize feasibility and acceptability of a combined in-person and text message-delivered intervention designed to support community reentry and continuation of MOUD. Methods: Participants (n = 8), who had prior experience engaging in MOUD while in jail/prison, were recruited from an outpatient primary care clinic in Rhode Island. A semi-structured interview was conducted to assess barriers/facilitators to technology following release, experiences of community reentry and OUD treatment, perceptions of continuum of care, and feasibility/acceptability of the intervention. All interviews were coded independently by 2 research assistants. Results: Participants reacted positively toward an intervention designed to support the transition to community-based care. Most participants denied any apprehension about using this type of platform. Obtaining a cell phone following release was endorsed as generally viable; however, special consideration must be paid to the consistency of cell phone service as well as digital literacy. Participants readily agreed on the utility of structured, daily text messages that provide motivational reminders and distress tolerance skill suggestions as well as the opportunity to access "on-demand" support. Conclusion: Overall, individuals engaged in MOUD while in jail/prison were receptive to a motivational- and distress tolerance-based digital health intervention to support recovery. Incorporating thematic results on suggested structural changes may increase the usability of this intervention to promote continuation of MOUD following release from jail/prison.

New Drug Design Avenues Targeting Alzheimer's Disease by Pharmacoinformatics-Aided Tools.

Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer's disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.

Synthesis (Z) vs (E) Selectivity, Antifungal Activity against Fusarium oxysporum, and Structure-Based Virtual Screening of Novel Schiff Bases Derived from l-Tryptophan.

Schiff bases are widely used molecules due to their potential biological activity. In this manuscript, we presented the synthesis and NMR study of new enamine Schiff bases derived from l-tryptophan, showing that the Z-form of the enamine is the main tautomeric form for aliphatic precursors. The DFT-B3LYP methodology at the 6-311+G**(d,p) level suggested that the tautomeric imine forms are less stable than the corresponding enamine forms. Their isomerism depends on the formation of intramolecular hydrogen bonds and steric factors associated with the starting carbonyl precursors. The in vitro biological activity tests against Fusarium oxysporum revealed that acetylacetone derivatives are the most active agents (IC50 < 0.9 mM); however, the antifungal activity could be disfavored by bulky groups on ester and enamine moieties. Finally, the structure-based virtual screening through molecular docking and MM-GBSA rescoring revealed that Schiff bases 3e, 3g, and 3j behave putatively as binders for target proteins involved in the life processes of F. oxysporum. In this sense, molecular dynamics analysis showed that the ligand-protein complexes have good stability with root-mean-square deviation (RMSD) values within the allowed range. Therefore, the present study paves the way for designing new antifungal compounds based on l-tryptophan-derived Schiff bases.

High polarity extracts obtained from Ilex guayusa Loes. leaves, exhibit antioxidant capacity / Extractos de alta polaridad obtenidos a partir de las hojas de Ilex guayusa Loes. exhiben capacidad antioxidante

Background: Ilex guayusa Loes. belongs to the family Aquifoliaceae. It is an evergreen tree native to the Amazon region. According to traditional uses, it is used as a diaphoretic, narcotic, purgative, among other uses. Objective: To evaluate the antioxidant capacity, quantify phenols and total flavonoids of extracts obtained from Ilex guayusa leaves. Methods: Total ethanolic extract was obtained using Soxhlet-type equipment, with subsequent liquid/liquid fractionation with solvents of different polarities (petroleum ether, dichloromethane, and ethyl acetate); were reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+), determining the inhibitory concentration 50 (IC50) and relative antioxidant activity (%AAR), with subsequent statistical analysis (ANOVA and Tukey's post-hoc). Total phenols and flavonoids were quantified using the Folin-Ciocalteu method and complex formation with AlCl3, respectively. Results: The ethanolic extract of leaves showed the highest antioxidant activity in both the DPPH• and ABTS•+ methods with IC50 values of 4.58 and 3.82 ppm, respectively. Conclusions: According to the results obtained in this study, it was possible to corroborate that the ethanolic extract (EE) obtained from the leaves of I. guayusa showed the highest antioxidant capacity, by the DPPH• and ABTS•+ methods. Additionally, it was possible to relate this capacity to the high flavonoids content present in this extract. Based on the above and accompanied by future studies, the Ilex guayusa species could be proposed as an important source of antioxidant compounds with possible application in medicine and the food industry

Antecedentes:Ilex guayusa Loes. pertenece a la familia Aquifoliaceae. Es un árbol perenne, nativo de la región amazónica. De acuerdo con los usos tradicionales es empleada como diaforético, narcótico, purgativo, entre otros usos. Objetivo: Evaluar la capacidad antioxidante, cuantificar fenoles y flavonoides totales de extractos obtenidos a partir de las hojas de Ilex guayusa. Métodos: El extracto etanólico total se obtuvo mediante un equipo tipo "Soxhlet", con posterior fraccionamiento líquido/líquido con solventes de diferentes polaridades (éter de petróleo, diclorometano y acetato de etilo); se hicieron reaccionar con 2,2-difenil-1-picrilhidracilo (DPPH•) y ácido 2,2'-azino-bis-3-etilbenzotiazolin-6-sulfónico (ABTS•+), determinando la concentración inhibitoria 50 (IC50) y la actividad antioxidante relativa (%AAR), con posterior análisis estadístico (ANOVA y post-hoc de Tukey). Los fenoles y flavonoides totales se cuantificaron con el método de Folin-Ciocalteu y el de formación de complejos con AlCl3, respectivamente. Resultados: El extracto etanólico de las hojas fue el que presentó mayor actividad antioxidante tanto en el método DPPH• como en el ABTS•+ con valores de IC50 de 4,58 y 3,82 ppm, respectivamente. Conclusiones: De acuerdo con los resultados obtenidos en este estudio, se pudo corroborar que el extracto etanólico obtenido de las hojas de I. guayusamostró la mayor capacidad antioxidante, por los métodos DPPH• y ABTS•+. Adicionalmente, se pudo relacionar esta capacidad con el alto contenido de flavonoides presentes en este extracto. Con base en lo anterior y acompañado de futuros estudios, la especie I. guayusa podría proponerse como una importante fuente de compuestos antioxidantes con posible aplicación en los campos de la medicina y la industria alimentaria

A Compendium of the Most Promising Synthesized Organic Compounds against Several Fusarium oxysporum Species: Synthesis, Antifungal Activity, and Perspectives.

Vascular wilt caused by F. oxysporum (FOX) is one of the main limitations of producing several agricultural products worldwide, causing economic losses between 40% and 100%. Various methods have been developed to control this phytopathogen, such as the cultural, biological, and chemical controls, the latter being the most widely used in the agricultural sector. The treatment of this fungus through systemic fungicides, although practical, brings problems because the agrochemical agents used have shown mutagenic effects on the fungus, increasing the pathogen's resistance. The design and the synthesis of novel synthetic antifungal agents used against FOX have been broadly studied in recent years. This review article presents a compendium of the synthetic methodologies during the last ten years as promissory, which can be used to afford novel and potential agrochemical agents. The revision is addressed from the structural core of the most active synthetic compounds against FOX. The synthetic methodologies implemented strategies based on cyclo condensation reactions, radical cyclization, electrocyclic closures, and carbon-carbon couplings by metal-organic catalysis. This revision contributes significantly to the organic chemistry, supplying novel alternatives for the use of more effective agrochemical agents against F. oxysporum.

Muscle Precursor Cells Enhance Functional Muscle Recovery and Show Synergistic Effects With Postinjury Treadmill Exercise in a Muscle Injury Model in Rats.

BACKGROUND: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established. PURPOSE: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (105 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation. RESULTS: Red fluorescence-labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)-positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm2 and 686.0 ± 11.6 µm2, respectively) compared with the Vehicle group (247.5 ± 10.7 µm2), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%). CONCLUSION: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries. CLINICAL RELEVANCE: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.

PSC-db: A Structured and Searchable 3D-Database for Plant Secondary Compounds.

Plants synthesize a large number of natural products, many of which are bioactive and have practical values as well as commercial potential. To explore this vast structural diversity, we present PSC-db, a unique plant metabolite database aimed to categorize the diverse phytochemical space by providing 3D-structural information along with physicochemical and pharmaceutical properties of the most relevant natural products. PSC-db may be utilized, for example, in qualitative estimation of biological activities (Quantitative Structure-Activity Relationship, QSAR) or massive docking campaigns to identify new bioactive compounds, as well as potential binding sites in target proteins. PSC-db has been implemented using the open-source PostgreSQL database platform where all compounds with their complementary and calculated information (classification, redundant names, unique IDs, physicochemical properties, etc.) were hierarchically organized. The source organism for each compound, as well as its biological activities against protein targets, cell lines and different organism were also included. PSC-db is freely available for public use and is hosted at the Universidad de Talca.

Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT: a proof-of-concept study in a rat model.

BACKGROUND: Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. METHODS: Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. RESULTS: Optimal contrast agent dose was found to be 20 mL/kg injected at 400 µL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. CONCLUSION: Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.

Lithopedion in a geriatric patient

Abstract Lithopedion (lithos = rock and paidion = child) is a rare condition that only occurs in 1.5 to 1.8% of extrauterine pregnancies and in 0.00045% of all pregnancies. It consists of an ectopic pregnancy in which the fetus dies but cannot be reabsorbed by the mother's body, which then coats it in a calcium-rich substance.We present the case of a 77-year-old woman with an incidental diagnosis of a lithopedion, which had been retained in her left pelvis for presumably 40 years.