Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients.

Epidemiological studies show that having a history of cancer protects from the development of Alzheimer's Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer's Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-ß-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.

Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. Traditionally, two therapeutic strategies have been employed for its treatment: heart rate control and rhythm control. Recent clinical studies have emphasized the critical role of early restoration of sinus rhythm in improving patient outcomes. The persistence of the irregular rhythm allows for the progression and structural remodeling of the atria, eventually leading to irreversible stages, as observed clinically when AF becomes permanent. Cardioversion to sinus rhythm alters this progression pattern through mechanisms that are still being studied. In this review, we provide an in-depth analysis of the pathophysiological mechanisms responsible for maintaining AF and how they are modified during sinus rhythm restoration using existing therapeutic strategies at different stages of clinical investigation. Moreover, we explore potential future therapeutic approaches, including the promising prospect of gene therapy.

A partially averaged system to model neuron responses to interferential current stimulation.

The interferential current (IFC) therapy is a noninvasive electrical neurostimulation technique intended to activate deep neurons using surface electrodes. In IFC, two independent kilohertz-frequency currents purportedly intersect where an interference field is generated. However, the effects of IFC on neurons within and outside the interference field are not completely understood, and it is unclear whether this technique can reliable activate deep target neurons without side effects. In recent years, realistic computational models of IFC have been introduced to quantify the effects of IFC on brain cells, but they are often complex and computationally costly. Here, we introduce a simplified model of IFC based on the FitzHugh-Nagumo (FHN) model of a neuron. By considering a modified averaging method, we obtain a non-autonomous approximated system, with explicit representation of relevant IFC parameters. For this approximated system we determine conditions under which it reliably approximates the complete FHN system under IFC stimulation, and we mathematically prove its ability to predict nonspiking states. In addition, we perform numerical simulations that show that the interference effect is observed only for a narrow set of IFC parameters and, in particular, for a beat frequency no higher than about 100 [Hz]. Our novel model tailored to the IFC technique contributes to the understanding of neurostimulation modalities using this type of signals, and can have implications in the design of noninvasive electrical stimulation therapies.

Both younger and elderly patients in pain are willing to undergo knee replacement despite the COVID-19 pandemic: a study on surgical waiting lists.

PURPOSE: To identify factors influencing patient's availability to re-schedule primary total knee replacement (TKR) or revision (RKR) surgery after the lockdown (March-May 2020) during the COVID-19 pandemic. METHODS: A prospective cohort study through a telephone survey was performed in 156 patients (143 for primary and 13 for revision) included in the TKR and RKR surgical waiting list before March 2020. Contact of each patient with COVID-19, stress and anxiety, perceived pain, and function were obtained in the interviews, and also the preference of each patient to have re-scheduled surgery (early or late). Finally, we registered their response (acceptance or refusal) when surgery was effectively re-scheduled. RESULTS: 88 out of 156 patients waiting for knee replacement (76/143 of those waiting for TKR, 12/13 of those waiting for RKR) declared themselves ready for surgery in less than 1 month. When re-scheduled, 115 patients underwent surgery and 41 refused. Significantly different preferences were found for age (more prone to surgery if under 65), revision surgery (more readily available), pain (7.9 ± 1.7/10 in NRS in those undergoing surgery, 5.6 ± 2.3/10 in those refusing, p = 0.000), or COVID-19 diagnosis, but not other close contact with COVID-19, comorbidities, stress, or anxiety. A logistic regression model confirmed that revision surgery (OR 9.33), perceived severe pain (OR 5.21), and age under 65 years (OR 5.82) were significantly associated with patient preference. The probability of patients over 65 to prefer early surgery reached 60% only with pain at or above 9/10. CONCLUSIONS: Surgical timing preferences for knee replacement vary between patients older than 65 years (immediate surgery only when pain is intense) and younger patients (immediate surgery no matter the amount of pain). Even if COVID-19 severely stroke our population, the need for knee replacement stood in the young population and even in the aged population at risk for COVID when pain was important.

Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Recent studies suggest that cellular senescence plays a role in Alzheimer's Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-ß-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.

Variation in plant belowground resource allocation across heterogeneous landscapes: implications for post-fire resprouting.

PREMISE: Resource availability affects biomass allocation in ways that could influence plant responses to disturbance such as fire. This is important because fire also varies across landscapes in ways that are correlated to resource availability. We hypothesized that plants growing in landscape microsites with a shortage of nutrients and water allocate more biomass and resources to belowground structures (and thus promote traits that enhance post-fire resprouting ability) than plants in more mesic sites. METHODS: We selected sites in three contrasting topographies (3 gullies, 3 midslopes, and 3 ridges) that supported different vegetation types and fire regimes, in Jalisco, Mexico. At each site, we measured soil nutrient and water content and light availability. Then we sampled biomass and root starch allocation in three post-fire resprouting shrubs that grow across a wide range of microenvironmental conditions. RESULTS: The ridges showed the highest values of solar radiation and the lowest of soil N and water content. Overall, we found a significant tendency for higher root-to-shoot (R/S) ratios, greater fine root biomass, and higher root starch content, in individuals growing in ridges or midslopes compared to the values of the plants living in gullies. CONCLUSIONS: Plants located in open canopy sites, characterized by a shortage of nutrients and water, tend to allocate more biomass belowground than plants in wet and fertile sites. Thus, plants in wet and fertile forests should be more vulnerable to increased disturbance such as wildfires.

Functional categorization of de novo transcriptome assembly of Vanilla planifolia Jacks. potentially points to a translational regulation during early stages of infection by Fusarium oxysporum f. sp. vanillae.

BACKGROUND: Upon exposure to unfavorable environmental conditions, plants need to respond quickly to maintain their homeostasis. For instance, physiological, biochemical and transcriptional changes occur during plant-pathogen interaction. In the case of Vanilla planifolia Jacks., a worldwide economically important crop, it is susceptible to Fusarium oxysporum f. sp. vanillae (Fov). This pathogen causes root and stem rot (RSR) in vanilla plants that lead to plant death. To investigate how vanilla plants, respond at the transcriptional level upon infection with Fov, here we employed the RNA-Seq approach to analyze the dynamics of whole-transcriptome changes during two-time frames of the infection. RESULTS: Analysis of global gene expression profiles upon infection by Fov indicated that the major transcriptional change occurred at 2 days post-inoculation (dpi), in comparison to 10 dpi. Briefly, the RNA-Seq analysis carried out in roots found that 3420 and 839 differentially expressed genes (DEGs) were detected at 2 and 10 dpi, respectively, as compared to the control. In the case of DEGs at 2 dpi, 1563 genes were found to be up-regulated, whereas 1857 genes were down-regulated. Moreover, functional categorization of DEGs at 2 dpi indicated that up-regulated genes are mainly associated to translation, whereas down-regulated genes are involved in cell wall remodeling. Among the translational-related transcripts, ribosomal proteins (RPs) were found increased their expression exclusively at 2 dpi. CONCLUSIONS: The screening of transcriptional changes of V. planifolia Jacks upon infection by Fov provides insights into the plant molecular response, particularly at early stages of infection. The accumulation of translational-related transcripts at early stages of infection potentially points to a transcriptional reprogramming coupled with a translational regulation in vanilla plants upon infection by Fov. Altogether, the results presented here highlight potential molecular players that might be further studied to improve Fov-induced resistance in vanilla plants.

Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance.

Adipo/cytokines in atherosclerotic secretomes: increased visfatin levels in unstable carotid plaque.

BACKGROUND: Novel pro-inflammatory and anti-inflammatory derivatives from adipose tissue, known as adipokines, act as metabolic factors. The aim of this study was to analyse the secreted expression of different adipo/cytokines in secretomes of unstable carotid atherosclerotic plaque versus non-atherosclerotic mammary artery. METHODS: We evaluated the secretion levels of adiponectin, visfatin, lipocalin-2, resistin, IL-6 and TNFR2 by ELISA in human secretomes from cultured unstable carotid atherosclerotic plaque (n = 18) and non-atherosclerotic mammary artery (n = 13). We also measured visfatin serum levels in patients suffering from atherosclerosis and in a serum cohort of healthy subjects (n = 16). RESULTS: We found that visfatin levels were significantly increased in unstable carotid atherosclerotic plaque secretome than in non-atherosclerotic mammary artery secretome. No differences were found with regard the other adipo/cytokines studied. Regarding visfatin circulating levels, there were no differences between unstable carotid atherosclerotic plaque and non-atherosclerotic mammary artery group. However, these visfatin levels were increased in comparison to serum cohort of healthy subjects. CONCLUSIONS: Of all the adipo/cytokines analysed, only visfatin showed increased levels in secretomes of unstable carotid atherosclerotic plaque. Additional human studies are needed to clarify the possible role of visfatin as prognostic factor of unstable carotid atherosclerotic plaque.

Optimal and safe treatment of spider leg veins measuring less than 1.5 mm on skin type IV patients, using repeated low-fluence Nd:YAG laser pulses after polidocanol injection.

Treatment of micro-veins of less than 1.5 mm with laser and with chemical sclerosis is technically challenging because of their difficulty to remedy. Laser treatment is even more difficult when dark phototypes are involved.Three groups of 30 patients each, skin type IV, and vessels measuring less than 1.5 mm in diameter, were enrolled for two treatment sessions 8 weeks apart: group A, polidocanol (POL) micro-foam injection; group B, Nd:YAG laser alone; and group C, laser after POL injection. Repeated 8-Hz low-fluence pulses, moving the hand piece over a 3-cm vein segment with an average of five laser passes maximum and with a total time irradiation of 1 s were used. Sixteen weeks after the second treatment, statistically, degree of clearance after examining photographs and patients satisfaction index, plotted on a visual analogue scale and comparing results of all three groups, results were significantly better for group C (p<0.0001). No significant differences in complications were noticed between the three groups. Efficacy of combining POL and laser proved safe and satisfactory in 96 % of patients using low-fluence laser pulses with a total cumulative energy in the 3 cm venous segment, lower than that of conventional treatment. Very few and transient complications were observed. POL foam injection followed by laser pulses is safe and efficient for vein treatment in dark-skinned patients.

Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure.

BACKGROUND: Oxidative stress may be a key pathophysiological mediator in the development and progression of heart failure (HF). The role of serum-free thiol concentrations, as a marker of systemic oxidative stress, in HF remains largely unknown. OBJECTIVE: The purpose of this study was to investigate associations between serum-free thiol concentrations and disease severity and clinical outcome in patients with new-onset or worsening HF. METHODS: Serum-free thiol concentrations were determined by colorimetric detection in 3802 patients from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Associations between free thiol concentrations and clinical characteristics and outcomes, including all-cause mortality, cardiovascular mortality, and a composite of HF hospitalization and all-cause mortality during a 2-years follow-up, were reported. RESULTS: Lower serum-free thiol concentrations were associated with more advanced HF, as indicated by worse NYHA class, higher plasma NT-proBNP (P < 0.001 for both) and with higher rates of all-cause mortality (hazard ratio (HR) per standard deviation (SD) decrease in free thiols: 1.253, 95% confidence interval (CI): 1.171-1.341, P < 0.001), cardiovascular mortality (HR per SD: 1.182, 95% CI: 1.086-1.288, P < 0.001), and the composite outcome (HR per SD: 1.058, 95% CI: 1.001-1.118, P = 0.046). CONCLUSIONS: In patients with new-onset or worsening HF, a lower serum-free thiol concentration, indicative of higher oxidative stress, is associated with increased HF severity and poorer prognosis. Our results do not prove causality, but our findings may be used as rationale for future (mechanistic) studies on serum-free thiol modulation in heart failure. Associations of serum-free thiol concentrations with heart failure severity and outcomes.

New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside and Back.

Heart failure with preserved ejection fraction (HFpEF) is a growing public health problem in nearly 50% of patients with heart failure. Therefore, research on new strategies for its diagnosis and management has become imperative in recent years. Few drugs have successfully improved clinical outcomes in this population. Therefore, numerous attempts are being made to find new pharmacological interventions that target the main mechanisms responsible for this disease. In recent years, pathological mechanisms such as cardiac fibrosis and inflammation, alterations in calcium handling, NO pathway disturbance, and neurohumoral or mechanic impairment have been evaluated as new pharmacological targets showing promising results in preliminary studies. This review aims to analyze the new strategies and mechanical devices, along with their initial results in pre-clinical and different phases of ongoing clinical trials for HFpEF patients. Understanding new mechanisms to generate interventions will allow us to create methods to prevent the adverse outcomes of this silent pandemic.

Surrogate Endpoints in Oncology: Overview of Systematic Reviews and Their Use for Health Decision Making in Mexico.

OBJECTIVES: The use of surrogate endpoints (SEs) for cancer drug approval in health systems is common. The objectives of this study were to identify systematic reviews (SRs) that evaluated the correlation of SEs with overall survival (OS) in cancer drugs to analyze the applications of approved cancer drugs with SEs in Mexico and to apply the validation framework proposed by the Institute for Quality and Efficiency in Health Care (IQWiG). METHODS: An overview of SRs was conducted according to Cochrane Collaboration methodology. Applications for approved cancer drugs with SEs in Mexico were analyzed. The IQWiG validation framework was applied to evaluate the SEs identified in the overview and in the applications in Mexico. RESULTS: A total of 85 SRs that assessed 192 SEs for different types of cancer were selected. According to the IQWiG model, only 2.5% of the SEs analyzed in the overview and only one of the applications in Mexico could be used as surrogates for OS because the reliability (methodological quality) of the SRs and the strength of the correlation of SEs with OS was mostly low (92%) and low (correlation coefficient r ≤ 0.7; 50.5%), respectively. Of the total number of cancer drugs approved in Mexico, 19.4% used SEs. CONCLUSIONS: Most SEs for different types of cancer could not be used as surrogates for OS according to the IQWiG model, and their use for the approval of cancer drugs in Mexico is generally not justified.

Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity.

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types - a lineage-specific sensory effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for cnidarian hair cell development are unknown. Here, we show that the class IV POU homeodomain transcription factor (POU-IV) - an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria - controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes - including the transmembrane receptor-encoding gene polycystin 1 - specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.

The Search for Quorum Sensing in Botrytis cinerea: Regulatory Activity of Its Extracts on Its Development.

Botrytis cinerea is a phytopathogenic fungus that causes large crop and post-harvest losses. Therefore, new and effective strategies are needed to control the disease and to reduce resistance to fungicides. Modulating pathogenicity and virulence by manipulating microbial communication is a promising strategy. This communication mechanism, called Quorum Sensing (QS), has already been reported in bacteria and yeasts; however, it has not yet been studied in B. cinerea. To establish the existence of this biochemical process in B. cinerea, we prepared extracts at different growth times (D1-D12), which were applied to fresh cultures of the same fungi. The chemical analysis of the extracts obtained from several fermentations showed different compositions and biological activities. We confirmed the presence of several phytotoxins, as well as compounds 1-phenylethanol and 3-phenylpropanol. Day five extract (0.1%) inhibited conidia germination and elongation of germ tubes, day seven extract (1%) produced the greatest phytotoxic effect in tomato leaves, and day nine extract (0.1%) was a sporulation inhibitor. In contrast, the extracts from days 7, 9, and 12 of fermentation (0.1% and 0.01%) promoted pellet and biofilm formation. Sporulation was slightly induced at 0.01%, while at 0.1% there was a great inhibition. At the highest extract concentrations, a biocidal effect was detected, but at the lowest, we observed a QS-like effect, regulating processes such as filamentation, morphogenesis, and pathogenesis. These results of the biological activity and composition of extracts suggest the existence of a QS-like mechanism in B. cinerea, which could lead to new non-biocidal alternatives for its control through interference in the pathogenicity and virulence mechanisms of the fungi.

Descemet membrane endothelial keratoplasty and corneal biomechanics. / Queratoplastia endotelial de la membrana de Descemet y biomecánica corneal.

OBJECTIVE: To study the behaviour of the biomechanical properties of the cornea in DMEK (Descemet membrane endothelial keratoplasty). METHOD: Prospective longitudinal observational study. 21 pre and post-DMEK eyes. 3-month follow-up with the dynamic Scheimpflug Analyzer (Corvis ST, Oculus; Wetzlar, Germany). The following parameters were measured: IOPnc: non-corrected intraocular pressure (IOP), IOPb: IOP corrected by biomechanics, maximum deflection amplitude (DefA), CCT: central corneal pachymetry, flattening speed 1 and 2, peak distance, HC deformation amplitude: deformation amplitude in maximum concavity, integrated inverse concave radius, DAR 1 and 2: deformation amplitude at 1mm and 2mm from the corneal apex, respectively. ARTh: Ambrosial pachymetric ratio, SP1: stiffness parameter, CBI: Corvis Biomechanical index and the maximum inverse radius. Pre-operative and post-operative measurements were performed with a 3-month follow-up and compared with a paired sample t-test. RESULTS: There was a significant decrease in the IOPnc of 1.54±3mmHg (p<0.05), a significant increase in the post-surgical IOPb of 3.79±3.18mmHg (p<0.001), a significant pachymetric decrease of 164.4±91.35µm (p<0.001) after the intervention. All dynamic parameters of the Scheimpflug analyzer changed significantly after surgery (p<0.05), except the ARTh and IWC variables. CONCLUSIONS: Variables indicate a decrease in corneal strength post-DMEK, with an increase in IOPb, at least the first 3 months after surgery. This finding is especially relevant in the follow-up of patients with coexisting glaucoma.

The masked seducers: Lek courtship behavior in the wrinkle-faced bat Centurio senex (Phyllostomidae).

Centurio senex is an iconic bat characterized by a facial morphology deviating far from all other New World Leaf Nosed Bats (Phyllostomidae). The species has a bizarrely wrinkled face and lacks the characteristic nose leaf. Throughout its distribution from Mexico to Northern South America the species is most of the time rarely captured and only scarce information on its behavior and natural history is available. Centurio senex is frugivorous and one of the few bats documented to consume also hard seeds. Interestingly, the species shows a distinct sexual dimorphism: Adult males have more pronounced facial wrinkles than females and a fold of skin under the chin that can be raised in style of a face mask. We report the first observations on echolocation and mating behavior of Centurio senex, including synchronized audio and video recordings from an aggregation of males in Costa Rica. Over a period of 6 weeks we located a total of 53 perches, where during the first half of the night males were hanging with raised facial masks at a mean height of 2.35 m. Most of the time, the males moved just their wing tips, and spontaneously vocalized in the ultrasound range. Approaches of other individuals resulted in the perching male beating its wings and emitting a very loud, low frequency whistling call. Following such an encounter we recorded a copulation event. The observed aggregation of adult C. senex males is consistent with lek courtship, a behavior described from only few other bat species.

Nanoscale Perovskite-Sensitized Solar Cell Revisited: Dye-Cell or Perovskite-Cell?

A general and straightforward way of preparing few-nanometer-sized well-separated MAPbIx Br3-x (MA=methylammonium) perovskite photosensitizers on the surface of an approximately 1 µm thick mesoporous TiO2 photoanode was suggested through a two-step sequential deposition of low-concentrated lead halides (0.10-0.30 m PbI2 or PbBr2 ) and methylammonium iodide/bromide (MAI/MABr). When those nanoscale MAPbIx Br3-x perovskites were incorporated as a photosensitizer in typical solid-state dye-sensitized solar cells (ss-DSSCs), it could be verified clearly by the capacitance analysis that nano-particulate MAPbI3 perovskites play the same role as that of a typical dye sensitizer (MK-2 molecule) although their size, composition, and structure are different.

Validation of a long bone fracture non-union healing score after treatment with mesenchymal stromal cells combined to biomaterials.

The available scores to clinically evaluate fracture consolidation encounter difficulties to interpret progression towards consolidation in long-bone non-union, particularly when incorporating biomaterials in the surgical treatment. The aims of this study were to validate the REBORNE bone healing scale in tibia, humerus and femur non-unions treated by a combination of mesenchymal stromal cells (MSCs) and biomaterials, through the interclass correlation (ICC) among raters, and to define reliability and concordance in anteroposterior and lateral radiographs, compared to computed tomography (CT). METHODS: Twenty-six cases from the EudraCT 2011-005441-13 clinical trial underwent bone healing evaluation, if at least 3 out of 4 cortical views clearly identified. Three senior orthopaedic surgeons evaluated radiographs and CTs at 3 and 6 months FU. All cases included preoperative imaging and radiographs at 12 months. The 4-stage scale score was obtained from each cortical view in orthogonal radiographs or CTs. A score of 0.6875 (11/16) was set as a threshold for bone healing. Statistically, ICC evaluated agreement among raters. Cronbach's alpha coefficient tested reliability. Lin's concordance correlation coefficients (CCC) were estimated between mean CT scores and mean radiographic scores. Bland and Altman graphs provided the limits of agreement between both imaging techniques. Sensitivity and specificity were assessed in radiographs (against CT), and the Area Under the Receiver Operating Characteristics (ROC) Curve was estimated. The probability to predict bone consolidation with REBORNE scores obtained from radiographs was modelled. RESULTS: An ICC of 0.88 and 0.91 (CT and radiographs) confirmed agreement in the REBORNE score for non-union bone healing, with an inter-rater reliability of 0.92 and 0.95. Scores through the radiographic evaluation were found equivalent to the CTs at 6 months FU. A CCC of 0.79 was detected against CT. The radiographic scores in the REBORNE bone healing scale correctly classified bone consolidation in 77%, with an accuracy of 83% based on ROC curves. CONCLUSIONS: The REBORNE score measured with CT or radiographic images was reliable among raters at a follow-up time above 6 months for long bone non-union fractures. The REBORNE scale measured with radiographs proved valid to assess consolidation against CT measurements.

Outcomes of abdominal wall reconstruction in patients with the combination of complex midline and lateral incisional hernias.

BACKGROUND: The best treatment for the combined defects of midline and lateral incisional hernia is not known. The aim of our multicenter study was to evaluate the operative and patient-reported outcomes using a modified posterior component separation in patients who present with the combination of midline and lateral incisional hernia. METHODS: We identified patients from a prospective, multicenter database who underwent operative repairs of a midline and lateral incisional hernia at 4 centers with minimum 2-year follow-up. Hernias were divided into a main hernia based on the larger size and associated abdominal wall hernias. Outcomes reported were short- and long-term complications, including recurrence, pain, and bulging. Quality of life was assessed with the European Registry for Abdominal Wall Hernias Quality of Life score. RESULTS: Fifty-eight patients were identified. Almost 70% of patients presented with a midline defect as the main incisional hernia. The operative technique was a transversus abdominis release in 26 patients (45%), a modification of transversus abdominis release 27 (47%), a reverse transversus abdominis release in 3 (5%), and a primary, lateral retromuscular preperitoneal approach in 2 (3%). Surgical site occurrences occurred in 22 patients (38%), with only 8 patients (14%) requiring procedural intervention. During a mean follow-up of 30.1 ± 14.4 months, 2 (3%) cases of recurrence were diagnosed and required reoperation. There were also 4 (7%) patients with asymptomatic but visible bulging. The European Registry for Abdominal Wall Hernias Quality of Life score showed a statistically significant decrease in the 3 domains (pain, restriction, and cosmetic) in the postoperative score compared with the preoperative score. CONCLUSION: The different techniques of posterior component separation in the treatment of combined midline and lateral incisional hernia show acceptable results, despite the associated high complexity. Patient-reported outcomes after measurement of the European Registry for Abdominal Wall Hernias Quality of Life score demonstrated a clinically important improvement in quality of life and pain.