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We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20⯵g/g body weight (BW) GTE by gavage; the GEN group received 100â¯mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.
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Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.
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Gerbillinae , Próstata , Receptores Androgénicos , Privación de Sueño , Testosterona , Animales , Masculino , Privación de Sueño/metabolismo , Privación de Sueño/patología , Próstata/metabolismo , Próstata/patología , Testosterona/sangre , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Corticosterona/sangre , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Castración , Andrógenos/metabolismoRESUMEN
Human RAD52 protein binds DNA and is involved in genomic stability maintenance and several forms of DNA repair, including homologous recombination and single-strand annealing. Despite its importance, there are very few structural details about the variability of the RAD52 ring size and the RAD52 C-terminal protein-protein interaction domains. Even recent attempts to employ cryogenic electron microscopy (cryoEM) methods on full-length yeast and human RAD52 do not reveal interpretable structures for the C-terminal half that contains the replication protein A (RPA) and RAD51 binding domains. In this study, we employed the monodisperse purification of two RAD52 deletion constructs and small angle X-ray scattering (SAXS) to construct a structural model that includes RAD52's RPA binding domain. This model is of interest to DNA repair specialists as well as for drug development against HR-deficient cancers.
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SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., Stenotrophomonas maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of S. aureus, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., S. maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.
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The need to increase food production to address the world population growth can only be fulfilled with precision agriculture strategies to increase crop yield with minimal expansion of the cultivated area. One example is site-specific fertilization based on accurate monitoring of soil nutrient levels, which can be made more cost-effective using sensors. This study developed an impedimetric multisensor array using ion-selective membranes to analyze soil samples enriched with macronutrients (N, P, and K), which is compared with another array based on layer-by-layer films. The results obtained from both devices are analyzed with multidimensional projection techniques and machine learning methods, where a decision tree model algorithm chooses the calibrations (best frequencies and sensors). The multicalibration space method indicates that both devices effectively distinguished all soil samples tested, with the ion-selective membrane setup presenting a higher sensitivity to K content. These findings pave the way for more environmentally friendly and efficient agricultural practices, facilitating the mapping of cropping areas for precise fertilizer application and optimized crop yield.
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Introduction: Sow mortality in the U.S. swine industry has increased in recent years, for which pelvic organ prolapse (POP) is a major contributor, accounting for 21% of all sow mortality. Dysbiosis of microbial communities has been associated with disease and reproductive dysfunction in several species, and previous studies have shown changes in vaginal microbiota in sows with increased risk for POP during late gestation. However, there is insufficient knowledge surrounding the potential relationship between fecal microbiota and POP in sows. Therefore, the study objective was to identify differences in sow fecal microbiota and determine if fecal and vaginal microbial communities are correlated in relation to POP risk. Methods: Sows were evaluated for POP risk using an established perineal scoring system, with a perineal score (PS) of 1 (PS1) presuming little to no risk of POP to a PS of 3 (PS3) presuming high risk of POP. In the current study, 2,864 sows were scored during gestation week 15, and 1.0%, 2.7%, and 23.4% of PS1, PS2, and PS3 sows, respectively, subsequently experienced POP. Fecal swabs (n = 215) were collected between gestation days 108-115, DNA was extracted, and 16S rRNA gene amplicon sequencing libraries were analyzed using mothur, phyloseq and SAS in reference to PS and POP outcome. Additionally, co-occurrence networks were constructed using CoNet to compare fecal and vaginal microbiota from the same cohort of sows and identify correlations between different taxa. Results: Differences in fecal community composition (PERMANOVA; P < 0.05), structure (alpha diversity measurements; P < 0.05), and 13 individual operational taxonomic units (OTUs) were revealed between PS1 and PS3 assigned sows. No differences in fecal microbiota were detected as a result of POP outcome. However, the abundances of several taxa were correlated across sample collection sites, suggesting the fecal and vaginal microbial communities may be related to one another. Discussion: Collectively, fewer differences in the fecal microbiota exist in sows with differing risk for POP compared to the vaginal microbiota, suggesting the vaginal microbiome may be more relevant in relation to POP outcome, although correlations between fecal and vaginal communities may provide insight for strategies to combat POP.
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Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2â-) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O22-) or hydroperoxide (HO2-) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.
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Superóxido Dismutasa , Humanos , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Manganeso/metabolismo , Manganeso/química , Transporte de Electrón , Oxidación-Reducción , Espectroscopía de Absorción de Rayos X , Superóxidos/metabolismo , Superóxidos/química , Protones , Electrones , Modelos Moleculares , Oxígeno/metabolismo , Oxígeno/químicaRESUMEN
Proliferating cell nuclear antigen (PCNA), the homotrimeric eukaryotic sliding clamp protein, recruits and coordinates the activities of a multitude of proteins that function on DNA at the replication fork. Chromatin assembly factor 1 (CAF-1), one such protein, is a histone chaperone that deposits histone proteins onto DNA immediately following replication. The interaction between CAF-1 and PCNA is essential for proper nucleosome assembly at silenced genomic regions. Most proteins that bind PCNA contain a PCNA-interacting peptide (PIP) motif, a conserved motif containing only eight amino acids. Precisely how PCNA is able to discriminate between binding partners at the replication fork using only these small motifs remains unclear. Yeast CAF-1 contains a PIP motif on its largest subunit, Cac1. We solved the crystal structure of the PIP motif of CAF-1 bound to PCNA using a new strategy to produce stoichiometric quantities of one PIP motif bound to each monomer of PCNA. The PIP motif of CAF-1 binds to the hydrophobic pocket on the front face of PCNA in a similar manner to most known PIP-PCNA interactions. However, several amino acids immediately flanking either side of the PIP motif bind the IDCL or C-terminus of PCNA, as observed for only a couple other known PIP-PCNA interactions. Furthermore, mutational analysis suggests positively charged amino acids in these flanking regions are responsible for the low micromolar affinity of CAF-1 for PCNA, whereas the presence of a negative charge upstream of the PIP prevents a more robust interaction with PCNA. These results provide additional evidence that positive charges within PIP-flanking regions of PCNA-interacting proteins are crucial for specificity and affinity of their recruitment to PCNA at the replication fork.
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Factor 1 de Ensamblaje de la Cromatina , Modelos Moleculares , Antígeno Nuclear de Célula en Proliferación , Unión Proteica , Saccharomyces cerevisiae , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Nuclear de Célula en Proliferación/química , Antígeno Nuclear de Célula en Proliferación/genética , Factor 1 de Ensamblaje de la Cromatina/metabolismo , Factor 1 de Ensamblaje de la Cromatina/química , Factor 1 de Ensamblaje de la Cromatina/genética , Cristalografía por Rayos X , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Secuencias de Aminoácidos , Sitios de Unión , Secuencia de Aminoácidos , Conformación ProteicaRESUMEN
BACKGROUND: Gender representation trends at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Annual Meetings and the effect of the 2018 'We R SAGES' initiatives are unknown. We assessed gender trends in oral presentations at the SAGES Annual Meeting between 2012 and 2022 with a focus on assessing the impact of the 2018 initiatives. METHODS: Abstracts selected for oral presentations from 2012 to 2022 were reviewed for presenter and first, second, and senior author gender. Gender was categorized as woman, man, or unknown using public professional profiles. Subsequent publications were identified using search engines. The primary outcome was the temporal trend of proportion of women in each role using interrupted time series analysis. Secondary outcomes included publication rates based on first and senior author genders in 2012-2018 versus 2019-2022. RESULTS: 1605 abstracts were reviewed. The proportion of women increased linearly in all categories: presenter (2.4%/year, R2 = 0.91), first author (2.4%/year, R2 = 0.90), senior author (2%/year, R2 = 0.65), and overall (2.2%, R2 = 0.91), (p < 0.01 for all). Prior to 2018, the proportion of women increased annually for presenters (coefficient: 0.026, 95% CI [0.016, 0.037], p = 0.002) and first authors (coefficient: 0.026, 95% CI [0.016, 0.037], p = 0.002), but there was no significant increase after 2018 (p > 0.05). Female second author proportion increased annually prior to 2018 (coefficient: 0.012, 95% CI [0.003, 0.021], p = 0.042) and increased by 0.139 (95% CI [0.070, 0.208], p = 0.006) in 2018. Annual female senior author proportion did not significantly change after 2018 (p > 0.05). 1198 (75.2%) abstracts led to publications. Women were as likely as men to be first (79% vs 77%, p = 0.284) or senior author (79% vs 77%, p = 0.702) in abstracts culminating in publications. There was no difference in woman first author publication rate before and after 2018 (80% vs 79%, p = 1.000), but woman senior author publication rate increased after 2018 (71% vs 83%, p = 0.032). CONCLUSION: There was an upward trend in women surgeons' presentations and associated publications in the SAGES Annual Meetings over the last decade.
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Congresos como Asunto , Médicos Mujeres , Sociedades Médicas , Humanos , Femenino , Congresos como Asunto/estadística & datos numéricos , Sociedades Médicas/estadística & datos numéricos , Estudios Transversales , Médicos Mujeres/estadística & datos numéricos , Masculino , Estados Unidos , Autoria , Gastroenterología/estadística & datos numéricosRESUMEN
Gestational complications are common in radiological practice and can be identified and evaluated using various imaging methods. Each complication typically presents with specific imaging features; however, there is a lack of comprehensive literature that consolidates this information to facilitate a diagnostic algorithm and focused study. In this context, this review aims to revisit the theoretical basis of differentials in pregnancy-related complications, discussing classic imaging features and providing examples of key features for each diagnosis. The focus is on essential information for accurate diagnosis, emphasizing the role of radiologists in contributing to better outcomes.
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Cerebral palsy (CP) describes some upper motoneuron disorders due to non-progressive disturbances occurring in the developing brain that cause progressive changes to muscle. While longer sarcomeres increase muscle stiffness in patients with CP compared to typically developing (TD) patients, changes in extracellular matrix (ECM) architecture can increase stiffness. Our goal was to investigate how changes in muscle and ECM architecture impact muscle stiffness, gait and joint function in CP. Gracilis and adductor longus biopsies were collected from children with CP undergoing tendon lengthening surgery for hamstring and hip adduction contractures, respectively. Gracilis biopsies were collected from TD patients undergoing anterior cruciate ligament reconstruction surgery with hamstring autograft. Muscle mechanical testing, two-photon imaging and hydroxyproline assay were performed on biopsies. Corresponding data were compared to radiographic hip displacement in CP adductors (CPA), gait kinematics in CP hamstrings (CPH), and joint range of motion in CPA and CPH. We found at matched sarcomere lengths muscle stiffness and collagen architecture were similar between TD and CP hamstrings. However, CPH stiffness (R2 = 0.1973), collagen content (R2 = 0.5099) and cross-linking (R2 = 0.3233) were correlated to decreased knee range of motion. Additionally, we observed collagen fibres within the muscle ECM increase alignment during muscular stretching. These data demonstrate that while ECM architecture is similar between TD and CP hamstrings, collagen fibres biomechanics are sensitive to muscle strain and may be altered at longer in vivo sarcomere lengths in CP muscle. Future studies could evaluate the impact of ECM architecture on TD and CP muscle stiffness across in vivo operating ranges. KEY POINTS: At matched sarcomere lengths, gracilis muscle mechanics and collagen architecture are similar in TD patients and patients with CP. In both TD and CP muscles, collagen fibres dynamically increase their alignment during muscle stretching. Aspects of muscle mechanics and collagen architecture are predictive of in vivo knee joint motion and radiographic hip displacement in patients with CP. Longer sarcomere lengths in CP muscle in vivo may alter collagen architecture and biomechanics to drive deficits in joint mobility and gait function.
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Parálisis Cerebral , Colágeno , Humanos , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/patología , Niño , Masculino , Femenino , Colágeno/metabolismo , Fenómenos Biomecánicos , Adolescente , Músculo Grácil , Rango del Movimiento Articular , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Marcha/fisiología , Músculos Isquiosurales/fisiología , Músculos Isquiosurales/fisiopatología , Matriz Extracelular/fisiologíaRESUMEN
Justification and objectives: The Spanish Academy of Dermatology and Venereology (AEDV) Psoriasis and Pediatric Working Groups (PSW and PWG) have developed a set of recommendations for the management of pediatric psoriasis based on the best available evidence and experts' opinion. Methodology: The methodology of nominal groups was followed, with help from a scoping review. A coordinator was designated, and a group of experts was selected based on their experience and knowledge on the management of psoriasis. The coordinator defined both the objectives and the key points of the document. Then, with help from a documentalist, a systematic literature review was conducted across Medline, Embase and Cochrane Library until May 2023. Systematic literature reviews, meta-analyses, and observational studies were included. National and international clinical practice guidelines and consensus documents were reviewed. With this information, the coordinator proposed preliminary recommendations that were discussed and modified in a nominal group meeting with all experts. After several review processes, which included an external review, the final document was generated. Results: Practical recommendations on the evaluation and management of patients with pediatric psoriasis are presented in association with other AEDV documents. The evaluation of the pediatric patient, the definition of the therapeutic objectives, the criteria for indication and selection of treatment are addressed. Practical issues such as therapeutic failure, response maintenance, comorbidity and risk management are also included.
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We develop a framework for on-the-fly machine learned force field molecular dynamics simulations based on the multipole featurization scheme that overcomes the bottleneck with the number of chemical elements. Considering bulk systems with up to 6 elements, we demonstrate that the number of density functional theory calls remains approximately independent of the number of chemical elements, in contrast to the increase in the smooth overlap of the atomic positions scheme.
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INTRODUCTION: Pathogenic variants in the gene encoding for BMPR2 are a major genetic risk factor for heritable pulmonary arterial hypertension (PAH). Due to incomplete penetrance, deep-phenotyping of unaffected carriers (UCs) of a pathogenic BMPR2 variant through multi-modality screening may aid in early diagnosis and identify susceptibility traits for future development of PAH. METHODS: 28 UCs (44±16â years, 57% female) and 21 healthy controls (43±18â years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging (cMRI), transthoracic echocardiography (TTE), cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC). Right ventricular (RV) pressure-volume (PV) loops were constructed to assess load independent contractility and compared with a healthy control group. A transgenic Bmpr2Δ71Ex1/+ rat model was employed to validate findings in humans. RESULTS: UCs had lower indexed right ventricular end-diastolic (80±18â mL·m-2 versus 64±14â mL·m-2;p= 0.003), end-systolic (34±11â mL·m-2 versus 27±8â mL·m-2;p=0.024) and left end-diastolic volumes (69±14â mL·m-2 versus 60±11â mL·m-2;p=0.019) than control subjects. Bmpr2Δ71Ex1/+ rats were also observed to have smaller cardiac volumes than WT rats. PV loop analysis showed significantly higher afterload (Ea) (0.15±0.06 versus 0.27±0.08; p<0.001), and end-systolic elastance (Ees) 0.28±0.07 versus 0.35±0.10; p=0.047) in addition to lower RV-pulmonary artery coupling (Ees/Ea)(2.24±1.03 versus 1.36±0.37; p=0.006) in UCs. During the 4-year follow-up period, two UCs developed PAH with normal NT-proBNP and TTE indices at diagnosis. CONCLUSION: Unaffected BMPR2 mutation carriers have an altered cardiac phenotype mimicked in Bmpr2Δ71Ex1/+ transgenic rats. Future efforts in establishing an effective screening protocol for individuals at risk for developing PAH warrants longer follow-up periods.
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PURPOSE: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events. METHODS: Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence's certainty. RESULTS: From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events. CONCLUSIONS: Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.
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Erectile dysfunction (ED) is a common issue that aging men encounter, but whether internalized gay ageism (i.e., the internalization of ageist messages within the context of aging as a gay man) is related to ED among older gay men is unknown. A cross-sectional web-based survey explored the relationship between internalized gay ageism, health-related and social factors, and ED among older gay men who resided in the Midwest United States (N = 181). Internalized gay ageism was not significantly associated with ED. However, hierarchical regression analysis found that age (ß = .224, t = 2.70, p = .008) and overall health (ß = -.247, t = -3.05, p = .003) were significantly associated with ED among older gay men, suggesting that older gay men share similar risk factors for ED as the general male population. Future research should continue to explore other factors that are unique to gay men that may be associated with ED.
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Disfunción Eréctil , Homosexualidad Masculina , Humanos , Masculino , Disfunción Eréctil/psicología , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Persona de Mediana Edad , Estudios Transversales , Anciano , Ageísmo/psicología , Factores de Riesgo , Encuestas y Cuestionarios , Minorías Sexuales y de Género/psicología , Minorías Sexuales y de Género/estadística & datos numéricosRESUMEN
OBJECTIVE: Short distances between the lowest visceral/renal artery and the aortic bifurcation are technically challenging during complex endovascular aortic aneurysm repair (EVAR), particularly after previous infrarenal repair. Traditionally, inverted limb bifurcated devices have been used in addition to fenestrated-branched (FB) endografts, but short overlap, difficult cannulation, and potential crushing of bridging stents are limitations for their use. This study reviews the early experience of patient-specific company manufactured devices (PS-CMDs) with a unibody bifurcated FB design for complex EVAR. METHODS: Consecutive complex EVAR procedures over a 34-month period with unibody bifurcated FB-devices as part of physician-sponsored investigational device exemption studies at two institutions were reviewed. Unibody bifurcated FB designs included FB bifurcated or fenestrated inverted limb devices. End points included technical success, survival, frequency of type I or III endoleaks, limb occlusion, and secondary interventions. RESULTS: Among 168 patients undergoing complex EVAR, 33 patients (19.6%; 78.7% male; mean age, 77 years) received unibody bifurcated FB PS-CMDs. FB bifurcated and fenestrated inverted limb devices were used in 31 (93.9%) and 2 (6.06%) patients, respectively. The median maximum aneurysm diameter was 61 mm (interquartile range [IQR], 55-69 mm). Prior EVAR was reported by 29 patients (87.9%), of whom 2 (6.06%) had suprarenal stents. A short distance between the lowest renal artery and aortic bifurcation was demonstrated in 30 patients (90.9%), with median distance of 47 mm (IQR, 38-54 mm). Preloaded devices were used in 23 patients (69.7%). A total of 128 fenestrations were planned; 22 (17.2%) were preloaded with guidewires and 5 (3.9%) with catheters. The median operative time was 238 minutes (226-300 minutes), with a median fluoroscopy time of 65.5 minutes (IQR, 56.0-77.7 minutes) and a median dose area product of 147 mGy∗cm2 (IQR, 105-194 mGy∗cm2). Exclusive femoral access was used in 14 procedures (42.4%). Technical success was 100%. Target vessel primary patency was 100% at a median follow-up time of 11.7 months (IQR, 3.5-18.6 months). Two patients (6.06%) required reintervention for iliac occlusion; one patient required stenting and the other a femoral-femoral bypass. No aortic-related deaths occurred after the procedure. During follow-up, 11 type II endoleaks (33.3%) and 1 type Ib endoleak (3.03%) were detected; the latter was treated with leg extension. No type Ia or III endoleaks occurred. CONCLUSIONS: Complex EVAR using unibody bifurcated FB-PS-CMDs is a simple, safe, and cost-effective alternative for the treatment of patients with short distances between the renal arteries and the aortic bifurcation. Further studies are required to assess benefits and durability of unibody bifurcated FB devices.
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AIM: To evaluate the mechanosensitivity of muscle satellite cells (MuSCs) and fibro-adipogenic progenitors (FAPs) in cerebral palsy (CP) and the efficacy of the drug verteporfin in restoring cells' regenerative capacity. METHOD: Muscle biopsies were collected from six children with CP and six typically developing children. MuSCs and FAPs were isolated and plated on collagen-coated polyacrylamide gels at stiffnesses of 0.2 kPa, 8 kPa, and 25 kPa. Cells were treated with verteporfin to block mechanosensing or with dimethyl sulfoxide as a negative control. MuSC differentiation and FAP activation into myofibroblasts were measured using immunofluorescence staining. RESULTS: Surprisingly, MuSC differentiation was not affected by stiffness; however, stiff substrates resulted in large myonuclear clustering. Across all stiffnesses, MuSCs from children with CP had less differentiation than those of their typically developing counterparts. FAP activation into myofibroblasts was significantly higher in children with CP than their typically developing peers, but was not affected by stiffness. Verteporfin did not affect differentiation or activation in either cell population, but slightly decreased myonuclear clustering on stiff substrates. INTERPRETATION: Cells from children with CP were less regenerative and more fibrotic compared to those of their typically developing counterparts, with MuSCs being sensitive to increases in stiffness. Therefore, the mechanosensitivity of MuSCs and FAPs may represent a new target to improve differentiation and activation in CP muscle.
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This paper presents a method for designing low carbon bio-based building materials, also named bio-concretes, produced with wood wastes in shavings form (WS) and cementitious pastes. As the aggregates phase of bio-concretes is composed of plant-based particles, known as porous and high water-absorbing materials, the bio-concretes cannot be designed by using the traditional design rules used for conventional mortar or concrete. Then, the method used in the current paper is an adaptation of a previous one that has been developed in a recent paper where bio-concretes were produced with a cement matrix, three types of bio-aggregates, and a proposal of a design abacus. However, when that abacus is used for designing WBC with low cement content in the matrix, the target compressive strength is not reached. In the present paper, the method is extended to low cement content matrix (up to 70% of cement substitution) and also considering the greenhouse gas (GHG) emission of the WBC. To obtain data for proposing a new design abacus, an experimental program was carried out by producing nine workable WBCs, varying wood volumetric fractions (40-45-50%), and water-to-binder ratios. The bio-concretes produced presented adequate consistency, lightness (density between 715 and 1207 kg/m3), and compressive strength ranging from 0.64 to 12.27 MPa. In addition, the GHG emissions of the WBC were analysed through the Life Cycle Assessment methodology. From the relationships obtained between density, compressive strength, water-to-binder ratio, cement consumption, and GHG emissions of the WBC, calibration constants were proposed for developing the updated and more complete abacus regarding an integrated mix design methodology.