Limitation of life support treatments in Spanish Intensive Care Units: Analysis of the ETHICUS II study.

OBJECTIVE: The aim of this study is to describe the results of Spanish ICUs in ETHICUS II study. DESIGN: Planned substudy of patients from ETHICUS II study. SETTING: 12 Spanish ICU. PATIENTS OR PARTICIPANTS: Patients admitted to Spanish ICU who died or in whom a limitation of life-sustaining treatment (LLST) was decided during a recruitment period of 6 months. INTERVENTIONS: Follow-up of patients was performed until discharge from the ICU and 2 months after the decision of LLST or death. MAIN VARIABLES OF INTEREST: Demographic characteristics, clinical profile, type of decision of LLST, time and form in which it was adopted. Patients were classified into 4 categories according to the ETHICUS II study protocol: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, failed cardiopulmonary resuscitation and patients with brain death. RESULTS: A total of 795 patients were analyzed; 129 patients died after CPR, 129 developed brain death. LLST was decided in 537 patients, 485 died in the ICU, 90.3%. The mean age was 66.19 years ± 14.36, 63.8% of male patients. In 221 (41%) it was decided to withdraw life-sustaining treatments and in 316 (59%) withholding life-sustaining treatments. Nineteen patients (2.38%) had advance living directives. CONCLUSIONS: The predominant clinical profile when LTSV was established was male patients over 65 years with mostly cardiovascular comorbidity. We observed that survival was higher in LLST decisions involving withholding of treatments compared to those in which withdrawal was decided. Spain has played a leading role in both patient and ICU recruitment participating in this worldwide multicenter study.

Systemic changes induced by autologous stem cell ovarian transplant in plasma proteome of women with impaired ovarian reserves.

Patients with poor ovarian response (POR) and premature ovarian insufficiency (POI) are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy in some cases. The Autologous stem cell ovarian transplantation (ASCOT) technique allows follicle development, enabling pregnancies and births of healthy babies in these patients. Previous results suggest that growth factors and cytokines secreted by stem cells are partially responsible for their regenerative properties. Indeed, ASCOT beneficial effects associate with the presence of different bone marrow derived stem cell- secreted factors in plasma. Therefore, the aim of this study was to assess whether ASCOT induce any modifications in the plasma proteomic profile of patients with impaired ovarian reserves. Discriminant analysis highlighted clear distinctions between the plasma proteome before (PRE), during stem cell mobilization and collection (APHERESIS) and three months after ASCOT (POST) in patients with POR and POI. Both the stem cell mobilization and ASCOT technique induced statistically significant modifications in the plasma composition, reversing some age-related protein expression changes. In the POR group, functional analysis revealed an enrichment in processes related to the complement cascade, immune system, and platelet degranulation, while in the POI group, enriched processes were also associated with responses to oxygen-containing compounds and growth hormones, and blood vessel maturation. In conclusion, our findings highlight the potential proteins and biological processes that may promote the follicle activation and growth observed after ASCOT. Identifying plasma proteins that regenerate aged or damaged ovaries could lead to more effective, targeted and/or preventive therapies for patients.

Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.

Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.

Optimisation and Characterisation of the Protein Hydrolysate of Scallops (Argopecten purpuratus) Visceral By-Products.

In this research, scallops (Argopecten purpuratus) visceral meal (SVM) and defatted meal (SVMD) were analysed for their proximal composition, protein solubility, and amino acid profile. Hydrolysed proteins isolated from the scallop's viscera (SPH) were optimised and characterised using response surface methodology with a Box-Behnken design. The effects of three independent variables were examined: temperature (30-70 °C), time (40-80 min), and enzyme concentration (0.1-0.5 AU/g protein) on the degree of hydrolysis (DH %) as a response variable. The optimised protein hydrolysates were analysed for their proximal composition, yield, DH %, protein solubility, amino acid composition, and molecular profile. This research showed that defatted and isolation protein stages are not necessaries to obtain the hydrolysate protein. The conditions of the optimization process were 57 °C, 62 min and 0.38 AU/g protein. The amino acid composition showed a balanced profile since it conforms to the Food and Agriculture Organisation/World Health Organisation recommendations for healthy nutrition. The predominant amino acids were aspartic acid + asparagine, glutamic acid + Glutamate, Glycine, and Arginine. The protein hydrolysates' yield and DH % were higher than 90% and close to 20%, respectively, with molecular weight between 1-5 kDa. The results indicate that the protein hydrolysates of scallops (Argopecten purpuratus) visceral by product optimised and characterised was suitable a lab-scale. Further research is necessary to study the bioactivity properties with biologic activity of these hydrolysates.

Characterizing Meat- and Milk/Dairy-like Vegetarian Foods and Their Counterparts Based on Nutrient Profiling and Food Labels.

Vegetarian foods are plant-based (PB) foods, often perceived as healthier foods than animal-based (AB) foods. The objective of this study was to analyze the nutritional quality of a set of PB foods (meat, milk and dairy products) marketed in Spain, and to compare their nutrient profiles with respect to some AB counterparts. Nutritional information per 100 g or mL, ingredients, and nutritional declarations, as well as the Nutri-Score, NOVA, and Eco-Score of each food were collected from Open Food Facts. Differences in the nutrient compositions between PB foods and their counterparts, and between the different groups of PB foods, were assessed at a 5% significance level. A total of 544 PB foods and 373 AB foods were identified. Overall, PB foods had a higher median content of fiber and carbohydrates, but a lower amount of proteins (except PB "meat" analogues: 14 g) and saturated fats (except PB "cheese alternatives": 12.5 g), than the AB counterparts (p < 0.05). PB "milk alternatives", particularly oat "milk", showed a higher median content of total carbohydrates (8 g) and sugars (5.5 g) compared to cow milks (4.7 g carbohydrates/sugars, on average; p < 0.001). PB "meat alternatives" also had a significantly higher value of carbohydrates (9 g) than AB meats (2 g, on average; p < 0.001). PB foods were mostly classified as Nutri-Score A and B (86%). However, more than half of them were of NOVA groups 3 and 4. Thus, there is a great diversity of PB meat and milk/dairy product alternatives on the Spanish market. Despite being products of good nutritional quality compared to AB foods, they also carry drawbacks that could have an impact on nutritional health.

Single intraovarian dose of stem cell- and platelet-secreted factors mitigates age-related ovarian infertility in a murine model.

BACKGROUND: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet. OBJECTIVE: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice. STUDY DESIGN: The effects of stem cells combined with activated platelet-rich plasma against age-related infertility were assessed following controlled ovarian stimulation in an aging murine model reproducing 3 physiological stages of women's reproductive life, namely young, advanced maternal age, and menopausal (n=12 animals per group). Female mice were randomized to receive a single intraovarian injection (10 µL/ovary) of either saline, activated platelet-rich plasma, or stem cells combined with activated platelet-rich plasma. Seven days later, the mice were stimulated, naturally mated, and sacrificed to harvest their ovaries for histologic assessment and molecular analysis and their oviducts to evaluate oocyte maturation and to assess early embryo development. RESULTS: A single intraovarian injection of stem cells combined with activated platelet-rich plasma promoted follicle activation and development in young, advanced maternal age, and old mice. Furthermore, stem cells combined with activated platelet-rich plasma rescued fertility in older mice by enhancing the quantity and quality of ovulated mature oocytes and supporting early embryo development to the blastocyst stage in all the evaluated ages. These fertility outcomes were positively associated with mitochondrial quality, treatment-increased mitochondrial DNA copy numbers, and reduced oxidative damage and apoptosis. Finally, the effects observed by histologic analysis were supported at the proteomic level. Functional proteomic analyses revealed molecular mechanisms involved in oocyte maturation and quality, mitochondrial function, and recovery of the ovarian stroma. CONCLUSION: Bone marrow-derived stem cells combined with activated platelet-rich plasma is a promising treatment with the potential to improve the reproductive outcomes of women with age-related infertility, exceeding the restorative effects of platelet-rich plasma alone. Although further research in human ovarian samples is still required, the autologous nature of stem cell factors collected by noninvasive mobilization, their combination with platelet-rich plasma, and the local administration route suggest that stem cells combined with activated platelet-rich plasma treatment could be a potentially effective and safe application for future clinical practice.

Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: an AEG and GETECCU collaborative cohort study.

BACKGROUND AND AIMS: Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence. METHODS: A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant. RESULTS: A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3-10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462-5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409-7.644; p < 0.001 for intermediate- and high- vs low-risk groups). CONCLUSIONS: Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

Antihypertensive and Antioxidant Activity of Chia Protein Techno-Functional Extensive Hydrolysates.

Twelve high-quality chia protein hydrolysates (CPHs) were produced from chia protein isolate (CPI) in a pilot plant of vegetable proteins. To obtain functional hydrolysate, four CPHs were hydrolyzed by the action of Alcalase, an endoprotease, and the other eight CPHs were hydrolyzed by the action of Flavourzyme, an exoprotease. Alcalase-obtained CPHs showed significant antihypertensive properties particularly, the CPH obtained after 15 min of hydrolysis with Alcalase (CPH15A), which showed a 36.2% hydrolysis degree. In addition, CPH15A increased the antioxidant capacity compared to CPI. The CPH15A physicochemical composition was characterized and compared to chia defatted flour (CDF) and CPI, and its techno-functional properties were determined by in vitro experiments through the analysis of its oil absorption capacity, as well as the capacity and stability of foaming and emulsifying, resulting in an emulsifier and stabilizer better than the intact protein. Therefore, the present study revealed that CPH15A has potent antihypertensive and antioxidant properties and can constitute an effective alternative to other plant protein ingredients sources that are being used in the food industry.

The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment.

In the two decades since the discovery of TNNI3K it has been implicated in multiple cardiac phenotypes and physiological processes. TNNI3K is an understudied kinase, which is mainly expressed in the heart. Human genetic variants in TNNI3K are associated with supraventricular arrhythmias, conduction disease, and cardiomyopathy. Furthermore, studies in mice implicate the gene in cardiac hypertrophy, cardiac regeneration, and recovery after ischemia/reperfusion injury. Several new papers on TNNI3K have been published since the last overview, broadening the clinical perspective of TNNI3K variants and our understanding of the underlying molecular biology. We here provide an overview of the role of TNNI3K in cardiomyopathy and arrhythmia covering both a clinical perspective and basic science advancements. In addition, we review the potential of TNNI3K as a target for clinical treatments in different cardiac diseases.

[ISAR Score (Identification of Seniors At Risk) predicts mortality in patients older than 75 years admitted in Intensive Care]. / ISAR Score (Identification of Seniors At Risk) predice la mortalidad en mayores de 75 años ingresados en Cuidados Intensivos.

BACKGROUND AND OBJECTIVES: Currently, the patient's baseline situation is a more important prognostic factor than age. The purpose of this study is to estimate the prognostic value of the ISAR score (Identification of Senior at Risk) in patients ≥75 years admitted to intensive care (ICU). PATIENTS AND METHODS: Prospective multicenter study including patients ≥75 years admitted to the ICU > 24hours. On admission, 28 days and 6 months after discharge from the ICU, mortality and baseline were evaluated using the ISAR score, the Lawton and Brody scale (LB) and the Barthel index (BI), the Frail fragility scale. scale (FS), the Charlson comorbidity index (ICC), Dementia rating score (DRC). RESULTS: 38 of 94 patients (40%) were high risk (ISAR ≥ 3) and were characterized by BI 90 (65-100), LB 4 (3-5), and CDR 1 (0-2), ICC 7.5 (6-10). 58% had FS ≥ 3. In the long term, they were in a situation of dependency [BI 50 (2.5-77.5), LB 3 (0-4), CDR 1 (0-1.5)]. The ICU mortality at 28 days and 6 months was 18.4%, 25.7% and 35.3%, respectively, being statistically significant. The area under the ISAR score ROC curve was 0.749 to 0.797, in all the mortality periods studied, although the difference with other predictive variables was not significant, but the p value was the lowest. CONCLUSIONS: The ISAR score predicts mortality in critically elderly patients with a discriminative capacity comparable to other predictive variables.

Dietary Fatty Acids in Postprandial Triglyceride-Rich Lipoproteins Modulate Human Monocyte-Derived Dendritic Cell Maturation and Activation.

Dietary fatty acids have been demonstrated to modulate systemic inflammation and induce the postprandial inflammatory response of circulating immune cells. We hypothesized that postprandial triglyceride-rich lipoproteins (TRLs) may have acute effects on immunometabolic homeostasis by modulating dendritic cells (DCs), sentinels of the immunity that link innate and adaptive immune systems. In healthy volunteers, saturated fatty acid (SFA)-enriched meal raised serum levels of granulocyte/macrophage colony-stimulating factor GM-CSF (SFAs > monounsaturated fatty acids (MUFAs) = polyunsaturated fatty acids (PUFAs)) in the postprandial period. Autologous TRL-SFAs upregulated the gene expression of DC maturation (CD123 and CCR7) and DC pro-inflammatory activation (CD80 and CD86) genes while downregulating tolerogenic genes (PD-L1 and PD-L2) in human monocyte-derived DCs (moDCs). These effects were reversed with oleic acid-enriched TRLs. Moreover, postprandial SFAs raised IL-12p70 levels, while TRL-MUFAs and TRL-PUFAs increased IL-10 levels in serum of healthy volunteers and in the medium of TRL-treated moDCs. In conclusion, postprandial TRLs are metabolic entities with DC-related tolerogenic activity, and this function is linked to the type of dietary fat in the meal. This study shows that the intake of meals enriched in MUFAs from olive oil, when compared with meals enriched in SFAs, prevents the postprandial production and priming of circulating pro-inflammatory DCs, and promotes tolerogenic response in healthy subjects. However, functional assays with moDCs generated in the presence of different fatty acids and T cells could increase the knowledge of postprandial TRLs' effects on DC differentiation and function.

Evaluation of Anti-Inflammatory and Atheroprotective Properties of Wheat Gluten Protein Hydrolysates in Primary Human Monocytes.

Bioactive protein hydrolysates have been identified in several sources as possible agents in the prevention and treatment of many diseases. A wheat gluten (WG) concentrate was hydrolyzed by Alcalase under specific conditions. The resulting hydrolysates were evaluated by in vitro cell-free experiments leading to the identification of one bioactive WG protein hydrolysate (WGPH), which was used at 50 and 100 µg/mL on primary human monocytes. Reactive oxygen species (ROS) and nitrite levels and RT-qPCR and ELISA techniques were used to analyze the functional activity of WGPH. Our results showed that WGPH hydrolyzed in 45 min (WGPH45A) down-regulated gene expression of Interleukin (IL)-1ß, IL-6, IL-17, and Interferon gamma (IFNγ) and reduced cytokine release in lipopolysaccharide (LPS)-stimulated monocytes. In addition, WGPH45A down-regulated gene-related to atherosclerotic onset. Our results suggest that WGPH45A has a potent anti-inflammatory and atheroprotective properties, reducing the expression of gene-related inflammation and atherosclerosis that could be instrumental in maintaining cardiovascular homeostasis.

Hemp (Cannabis sativa L.) Protein Hydrolysates Promote Anti-Inflammatory Response in Primary Human Monocytes.

Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide (LPS)-activated primary human monocytes. CD14+ cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate (HPI) and hydrolysates (HPHs) was evaluated on LPS-stimulated human primary monocytes. The specific markers of inflammation, polarization, and chemoattraction were measured by RT-qPCR and ELISA assays. Our results showed that HPPs decreased the pro-inflammatory mediators (TNFα, IL-1ß, and IL-6) and increased the anti-inflammatory mediators (IL-10 and IL-4). In addition, M1 polarization marker gene expression (CCR7 and iNOS) was downregulated by HPPs and, M2 polarization marker gene expression (CD200R and MRC1) was upregulated. Finally, the mRNA expression of chemotaxis genes (CCR2 and CCL2) was downregulated by HPPs. In conclusion, this study suggests that HPPs may improve chronic inflammatory states and promote regenerative processes by reprogramming monocytes toward M2 polarization phenotype.

Isolated Immunoglobulin G4-Related Disease of Nasal Septum and Maxilla: Diagnosis and Follow-up With 18F-FDG PET/CT.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition that can manifest in atypical locations. We present the case of a middle-aged woman presenting with isolated IgG4-RD of left maxilla and nasal septum, confirmed with F-FDG PET/CT. She achieved complete metabolic response with multiple pharmacologic treatment, but 1 year later, she experienced local relapse, and FDG PET/CT found new additional lesions in humeral vasculature and lungs. This case illustrates the usefulness of FDG PET/CT for initial evaluation and monitoring of IgG4-RD with unusual nasomaxillary involvement.

La ocupación en la Gerontología: una perspectiva crítica del Modelo de Ocupación Humana / Occupation in Gerontology: A critical perspective of the Model of Human Occupation / Ocupação em Gerontologia: uma perspectiva crítica do Modelo de Ocupação Humana

Desde la Terapia Ocupacional en el campo de la Gerontología, se propone una reflexión crítica sobre el uso del Modelo de Ocupación Humana en el abordaje de la ocupación en el envejecimiento, reconociendo la emergencia de la perspectiva crítica, los aportes del paradigma del curso de vida en la comprensión holística y contextual de la vejez, y la concepción de envejecimiento saludable. Se revisan los postulados principales del modelo en cuanto a la adaptación ocupacional, la volición, la habituación, la capacidad de desempeño y los entornos en la vejez. Se analiza la participación social en actividades significativas de la persona mayor en la construcción de la vida ocupacional y el rol de la narrativa en la adaptación ocupacional en el envejecimiento. Esta reflexión tiene implicaciones en la fundamentación de la intervención ocupacional en el envejecimiento, tanto desde la perspectiva terapéutica como en la promoción de la salud y la calidad de vida de las personas mayores. En definitiva, el análisis favorece el uso del Modelo de Ocupación Humana en la práctica profesional gerontológica.

A critical reflection of the Human Occupation Model is proposed to address the issue of occupation in aging, in the field of Occupational Therapy in Gerontology. It recognizes the emergence of a critical perspective, the contributions of vital course paradigm to the holistic and contextual understanding of old age, and the conception of healthy aging. The model's main postulates are reviewed in terms of occupational adaptation, volition, habituation, performance capacity and environments in old age. This reflection has implications for the fundamentals of occupational intervention in aging, both from a therapeutic perspective and the promotion of health and life quality in the elderly population. In conclusion, the analysis favors the use of the Human Occupation Model in gerontological professional practice.

A partir da Terapia Ocupacional no campo da Gerontologia, propõe-se uma reflexão crítica sobre a utilização do Modelo de Ocupação Humana na abordagem da ocupação no envelhecimento. Reconhece-se a emergência da perspectiva crítica, as contribuições do paradigma do curso de vida na compreensão holística e contextual do envelhecimento, bem como a concepção de envelhecimento saudável. Os principais postulados do modelo são revistos em termos de adaptação ocupacional, volição, habituação, capacidade de desempenho e ambientes na velhice. Analisa-se a participação social em atividades significativas dos idosos na construção da vida ocupacional, assim como o papel da narrativa na adaptação ocupacional do envelhecimento. Esta reflexão tem implicações na fundamentação da intervenção ocupacional no envelhecimento, tanto do ponto de vista terapêutico, como na promoção da saúde e qualidade de vida dos idosos. Definitivamente, a análise favorece a utilização do Modelo de Ocupação Humana na prática profissional gerontológica.

Neuroprotective protein hydrolysates from hemp (Cannabis sativa L.) seeds.

Hemp (Cannabis sativa L.) seeds are well known for their potential use as a source of nutrients, fiber, and bioactive compounds. A hemp protein isolate, prepared from defatted hemp flour, was hydrolyzed by alcalase and flavourzyme under specific conditions. The resulting hydrolysates were evaluated for the selection of potentially bioactive hemp protein hydrolysates (HPHs) owing to their DPPH scavenging and ferric reducing antioxidant power activity. In vitro cell-free experiments led to the identification of two bioactive HPHs, HPH20A and HPH60A + 15AF, which were used at 50 and 100 µg mL-1 on BV-2 microglial cells in order to evaluate the anti-neuroinflammatory activities. Our results showed that HPH20A and HPH60A + 15AF down-regulated TNF-α, IL-1ß, and IL-6 mRNA transcriptional levels in LPS-stimulated BV-2 microglial cells. In addition, HPH20A and HPH60A + 15AF up-regulated the gene expression of anti-inflammatory cytokine IL-10. This study suggests for the first time that HPHs may improve the neuroinflammatory and inflammatory states, supporting the nutraceutical value of hemp seeds.

Myc is dispensable for cardiomyocyte development but rescues Mycn-deficient hearts through functional replacement and cell competition.

Myc is considered an essential transcription factor for heart development, but cardiac defects have only been studied in global Myc loss-of-function models. Here, we eliminated Myc by recombining a Myc floxed allele with the Nkx2.5Cre driver. We observed no anatomical, cellular or functional alterations in either fetuses or adult cardiac Myc-deficient mice. We re-examined Myc expression during development and found no expression in developing cardiomyocytes. In contrast, we confirmed that Mycn is essential for cardiomyocyte proliferation and cardiogenesis. Mosaic Myc overexpression in a Mycn-deficient background shows that Myc can replace Mycn function, recovering heart development. We further show that this recovery involves the elimination of Mycn-deficient cells by cell competition. Our results indicate that Myc is dispensable in cardiomyocytes both during cardiogenesis and for adult heart homeostasis, and that Mycn is exclusively responsible for cardiomyocyte proliferation during heart development. Nonetheless, our results show that Myc can functionally replace Mycn We also show that cardiomyocytes compete according to their combined Myc and Mycn levels and that cell competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.

Subxiphoid uniportal video-assisted bilateral surgery: right upper lobectomy and left upper wedge resection S3.

Traditional approach of bilateral lesions usually involves bilateral approaches instead of classical thoracotomy or video-assisted thoracoscopic surgery (VATS) surgery, and often at two different times. During visit of Dr. Gonzalez Rivas at Master Class to Málaga, we performed right upper lobectomy and S3 wedge resection left upper lobe of a two synchronous bilateral lung lesions case with subxiphoid single incision approach. We are reporting the first case of a lobectomy combined with a wedge resection performed through an uniportal subxiphoid bilateral VATS in Spain.

Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in Europe.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main clinical manifestations involve the skin and the peripheral nervous system. Several types of nephropathy have been described in leprosy. One frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. In these patients, end-stage renal disease is an important contributor to morbidity and mortality. Here, we present the case of a patient with nephrotic syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a history of leprosy. The patient was correctly treated in her youth, which is the best way to avoid renal pathology, but she developed a nephrotic syndrome years later.

Mechanical characterization of sclerotic occlusal dentin by nanoindentation and nanoscratch.

PURPOSE: To evaluate the mechanical properties of occlusal wear lesions identified as sclerotic. METHODS: Nanoindentation and nanoscratch techniques have been applied to determine elastic modulus (E), hardness (H) and wear resistance of different types of sclerotic dentin. Nanoscratch testing was applied to evaluate the tribological behavior. Mechanical properties of sclerotic dentin were evaluated together with scanning electron micrographs to show the different degree of tubular occlusion. RESULTS: The higher the degree of sclerosis, the lower were the measured mechanical properties. The highest values (E = 20 GPa and H = 0.67 GPa) were obtained in normal dentin, and the lowest (E = 11.4 GPa and H = 0.51 GPa) in severe sclerotic lesions. These differences were statistically significant (P<0.05). The groove width in the nanoscratch tests was also higher for moderate or severe sclerosis than for normal dentin.