Nutritional Support Reduces Circulating Cytokines in Patients with Heart Failure.

Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.

Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia. / Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema.

INTRODUCTION AND OBJECTIVES: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). MATERIAL AND METHODS: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. RESULTS: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). CONCLUSIONS: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.

Occurrence and risk assessment of pesticides and their transformation products related to olive groves in surface waters of the Guadalquivir river basin.

Pesticides are considered one of the main sources of contamination of surface waters, especially in rural areas highly influenced by traditional agricultural practices. The objective of this work was to evaluate the impact caused by pesticides and their transformation products (TPs) related to olive groves in surface waters with strong agricultural pressure. 11 streams were monitored during four sampling campaigns over 2 years. A solid-phase extraction, followed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) analysis was used in the quantitative target approach, with more than 70 validated compounds. Target method was combined with a suspect screening strategy involving more than 500 pesticides and TPs, using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) to identify additional pesticides and TPs out of the scope of analysis. A total of 43 different compounds were detected with the target method. The herbicide MCPA was present in all samples and at the highest concentration (1260 ng L-1), followed by the fungicide carbendazim (1110 ng L-1), and the herbicide chlorotoluron (706 ng L-1). The suspect screening strategy revealed the presence of 7 compounds out of the target analysis (1 pesticide and 6 TPs). 6 analytes were confirmed with the analytical standards. Semi-quantification results revealed that TPs exhibited higher concentrations than their corresponding parent compounds, indicating higher persistency. Some small streams showed a comparable number of pesticides and concentrations to the most polluted large river. The determined pesticide and TPs concentrations represented an estimated environmental hazard in almost all sampling sites under study. This work underscores the importance of including pesticide TPs and small streams impacted by extensive agricultural activities in water quality monitoring programs.

Miniaturized flexible micro-tube plasma ionization source for the effective ionization of non-easily ionizable pesticides in food with liquid chromatography/mass spectrometry.

In this article, we have studied the potential of flexible microtube plasma (FµTP) as ionization source for the liquid chromatography high-resolution mass spectrometry detection of non-easily ionizable pesticides (viz. nonpolar and non-ionizable by acid/basic moieties). Phthalimide-related compounds such as dicofol, dinocap, o-phenylphenol, captan, captafol, folpet and their metabolites were studied. Dielectric barrier discharge ionization (DBDI) was examined using two electrode configurations, including the miniaturized one based on a single high-voltage (HV) electrode and a virtual ground electrode configuration (FµTP), and also the two-ring electrode DBDI configuration. Different ionization pathways were observed to ionize these challenging, non-easily ionizable nonpolar compounds, involving nucleophilic substitutions and proton abstraction, with subtle differences in the spectra obtained compared with APCI. An average sensitivity increase of 5-fold was attained compared with the standard APCI source. In addition, more tolerance with matrix effects was observed in both DBDI sources. The importance of the data reported is not just limited to the sensitivity enhancement compared to APCI, but, more notably, to the ability to effectively ionize nonpolar, late-eluting (in reverse-phase chromatography) non-ionizable compounds. Besides o-phenylphenol ([M - H]-), all the parent species were efficiently ionized through different mechanisms involving bond cleavages through the effect of plasma reagent species or its combination with thermal degradation and subsequent ionization. This tool can be used to figure out overlooked nonpolar compounds in different environmental samples of societal interest through non-target screening (NTS) strategies.

Does Donor Age Have Effects on Senescence Biomarkers in Kidney-Transplanted Patients?

Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements. We studied 61 patients subjected to renal transplant isolating blood samples 24 h before, and 24 h, 3 days, 7 days, 3 months, and 6 months after transplant. The patients were divided into three groups: older donor than the patient (Old Donor), younger donor than the patient (Young Donor), and similar age (Matched). We studied different senescence markers such as p16, p21, interleukin 6 (IL-6), and senescence-associated secretory phenotype (SASP) release. Young patients who receive older organs showed increased mRNA and protein expression of the senescence makers. Hence, increased SASP release was also observed in patients from older donor. In contrast, older patients who receive younger organs showed a slow but consistent improvement in their initial senescent phenotype. In addition, macrophage cell model treated with blood-derived serum from patients 6 months after the transplant showed a pro-senescence environment in macrophages proposed by the SASP from the patients. These results lead the hypothesis that senolytics could reduce the presence of senescent cells and mitigate the complications associated with the transplantation of older organs in young patients.

Regular Exercise Improved Fatigue and Musculoskeletal Pain in Young Adult Psoriatic Patients without Psoriatic Arthritis.

Fatigue and musculoskeletal pain are also frequent in patients with psoriasis (PsO) without arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with PsO without PsA. A total of 118 male patients with PsO volunteered in the current interventional study and were randomly allocated to the experimental (n = 59) or control group (n = 59). The intervention consisted of a 16-week aerobic training program on a treadmill, three sessions per week, consisting of a warm-up, 35-50 min treadmill exercise (increasing 5 min/4 weeks) at a work intensity of 50-65% of peak heart-rate (increasing 5%/4 weeks), and cooling-down. The functional assessment of chronic illness therapy fatigue scale (FACIT-Fatigue), health assessment questionnaire disability index (HAQ-DI), and visual analog scale (VAS) were compared pre and post intervention. Nutritional intake, maximal aerobic power, lipid profile, serum markers of muscle damage, and body composition were also assessed. When compared to baseline, FACIT-Fatigue, HAQ-DI, and VAS scores were significantly improved without increasing markers of muscle damage. Fat mass percentage, lipid profile, and maximal oxygen consumption were also improved. In conclusion, a 16-week aerobic training program at moderate intensity was safe, well tolerated, and effective in psoriatic patients without PsA. Long-term follow-up studies are required to examine whether these promising results may improve clinical outcomes.

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment.

Background: Obesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation. Aim: This study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities. Patients and methods: Epidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed. Results: Significant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia. Conclusion: The beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS.

Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, ß-propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate the autophagic defects and secondary pathological consequences in cellular models derived from two patients harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibroblasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. A transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with the accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron accumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochondrial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the expression levels of WDR45, neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidants partially improved cell physiopathology; however, autophagy and cell bioenergetics remained affected.

Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing.

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

Knowledge, Attitudes and Behaviours of Adolescents and Young Adult Population on the Use of E-Cigarettes or Personal Vaporizer.

The use of electronic cigarettes (e-cig) or personal vaporizers (PV) has increased in recent years, especially among adolescents and adults, increasing risk factors for their health or being a starting point for other risk behaviours. The aim of our study is to learn the knowledge, attitudes and behaviours of the adolescent and young adult population on the use of e-cigarettes or PVs. A cross-sectional descriptive study was carried out among 375 subjects. The use of e-cigs or PVs was measured using a self-administered questionnaire. Overall, 13.33% of the respondents used e-cigarettes or PVs. A correlation could be established between vape use and age, with 14-18-year-olds being the highest users (25.9%). Additionally, 90.13% of the respondents answered that e-cig or PV use was harmful to health. Other behaviours, such as consumption of energy drinks (ED), increases the probability of vaping by 3.08 times (CI = 1.55-6.29; p = 0.001). Subjects aged 23-26 years and 27-34 years are less likely to vape than subjects aged 14-18 years (OR = 0.31: CI = 0.09-0.96; p = 0.044; OR = 0.07: CI = 0.00-0.63; p = 0.037). The same applies to subjects with secondary education (OR = 0.17: CI = 0.04-0.66; p = 0.011) and postgraduate education (OR = 0.07: CI = 0.06-1.19; p = 0.043), than subjects with primary education. The use of e-cigs and PVs starts at an early age, despite the known harmful effects of e-cigs and PVs. Their use may occur mainly in recreational situations and in association with other substances such as ED.

Developmental Screening Tools Used with First Nations Populations: A Systematic Review.

Developmental surveillance and screening is recommended for all children under five years of age, especially for those from at-risk populations such as First Nations children. No review to date has, however, evaluated the use of developmental screening tools with First Nations children. This review aimed to examine and synthesise the literature on developmental screening tools developed for, or used with, First Nations populations children aged five years or younger. A PRISMA-compliant systematic review was performed in the PsychInfo, PubMed, and Embase databases. Additional searches were also undertaken. In total 444 articles were identified and 13 were included in the final review. Findings indicated that several developmental screening tools have been administered with First Nations children. Most tools, however, have only been evaluated in one study. Results also found that no studies evaluated actions taken following positive screening results. More research evaluating the accuracy, acceptability, and feasibility of using developmental screeners with First Nations children is required before widespread implementation of developmental screening in clinical settings with First Nations children is recommended.

Externacion Asistida / Assisted discharge

La experiencia sintetiza la trayectoria de Isabel, Graciela y Josefa por distintos dispositivos terapéuticos, como fueron "la casa de medio camino (1998-2016) y la casa de pre-alta (2001-2012) que favorecieron su autodeterminación personal.

The lysosomal proteome of senescent cells contributes to the senescence secretome.

Senescent cells accumulate in tissues over time, favoring the onset and progression of multiple age-related diseases. Senescent cells present a remarkable increase in lysosomal mass and elevated autophagic activity. Here, we report that two main autophagic pathways macroautophagy (MA) and chaperone-mediated autophagy (CMA) are constitutively upregulated in senescent cells. Proteomic analyses of the subpopulations of lysosomes preferentially engaged in each of these types of autophagy revealed profound quantitative and qualitative changes in senescent cells, affecting both lysosomal resident proteins and cargo proteins delivered to lysosomes for degradation. These studies have led us to identify resident lysosomal proteins that are highly augmented in senescent cells and can be used as novel markers of senescence, such as arylsulfatase ARSA. The abundant secretome of senescent cells, known as SASP, is considered their main pathological mediator; however, little is known about the mechanisms of SASP secretion. Some secretory cells, including melanocytes, use the small GTPase RAB27A to perform lysosomal secretion. We found that this process is exacerbated in the case of senescent melanoma cells, as revealed by the exposure of lysosomal membrane integral proteins LAMP1 and LAMP2 in their plasma membrane. Interestingly, a subset of SASP components, including cytokines CCL2, CCL3, CXCL12, cathepsin CTSD, or the protease inhibitor SERPINE1, are secreted in a RAB27A-dependent manner in senescent melanoma cells. Finally, proteins previously identified as plasma biomarkers of aging are highly enriched in the lysosomes of senescent cells, including CTSD. We conclude that the lysosomal proteome of senescent cells is profoundly reconfigured, and that some senescent cells can be highly active in lysosomal exocytosis.

Watch me grow integrated (WMG-I): protocol for a cluster randomised controlled trial of a web-based surveillance approach for developmental screening in primary care settings.

INTRODUCTION: The increasing prevalence of developmental disorders in early childhood poses a significant global health burden. Early detection of developmental problems is vital to ensure timely access to early intervention, and universal developmental surveillance is recommended best practice for identifying issues. Despite this, there is currently considerable variation in developmental surveillance and screening between Australian states and territories and low rates of developmental screening uptake by parents. This study aims to evaluate an innovative web-based developmental surveillance programme and a sustainable approach to referral and care pathways, linking primary care general practice (GP) services that fall under federal policy responsibility and state government-funded child health services. METHODS AND ANALYSIS: The proposed study describes a longitudinal cluster randomised controlled trial (c-RCT) comparing a 'Watch Me Grow Integrated' (WMG-I) approach for developmental screening, to Surveillance as Usual (SaU) in GPs. Forty practices will be recruited across New South Wales and Queensland, and randomly allocated into either the (1) WMG-I or (2) SaU group. A cohort of 2000 children will be recruited during their 18-month vaccination visit or opportunistic visit to GP. At the end of the c-RCT, a qualitative study using focus groups/interviews will evaluate parent and practitioner views of the WMG-I programme and inform national and state policy recommendations. ETHICS AND DISSEMINATION: The South Western Sydney Local Health District (2020/ETH01625), UNSW Sydney (2020/ETH01625) and University of Queensland (2021/HE000667) Human Research Ethics Committees independently reviewed and approved this study. Findings will be reported to the funding bodies, study institutes and partners; families and peer-reviewed conferences/publications. TRIAL REGISTRATION NUMBER: ANZCTR12621000680864.

Coordinated NADPH oxidase/hydrogen peroxide functions regulate cutaneous sensory axon de- and regeneration.

Tissue wounding induces cutaneous sensory axon regeneration via hydrogen peroxide (H2O2) that is produced by the epithelial NADPH oxidase, Duox1. Sciatic nerve injury instead induces axon regeneration through neuronal uptake of the NADPH oxidase, Nox2, from macrophages. We therefore reasoned that the tissue environment in which axons are damaged stimulates distinct regenerative mechanisms. Here, we show that cutaneous axon regeneration induced by tissue wounding depends on both neuronal and keratinocyte-specific mechanisms involving H2O2 signaling. Genetic depletion of H2O2 in sensory neurons abolishes axon regeneration, whereas keratinocyte-specific H2O2 depletion promotes axonal repulsion, a phenotype mirrored in duox1 mutants. Intriguingly, cyba mutants, deficient in the essential Nox subunit, p22Phox, retain limited axon regenerative capacity but display delayed Wallerian degeneration and axonal fusion, observed so far only in invertebrates. We further show that keratinocyte-specific oxidation of the epidermal growth factor receptor (EGFR) at a conserved cysteine thiol (C797) serves as an attractive cue for regenerating axons, leading to EGFR-dependent localized epidermal matrix remodeling via the matrix-metalloproteinase, MMP-13. Therefore, wound-induced cutaneous axon de- and regeneration depend on the coordinated functions of NADPH oxidases mediating distinct processes following injury.

Aplicación de células madres autólogas en pacientes con aterosclerosis obliterante grado IV / Application of autologous stem cells in patients with grade IV atherosclerosis obliterans

RESUMEN Introducción: la enfermedad arterial periférica de los miembros inferiores afecta a un elevado porcentaje de la población mundial, con las células madres autólogas obtenidas de sangre periférica se logra una mayor síntesis de factores de crecimiento que inducen la angiogénesis. Objetivo: describir el autotrasplante de células madres autólogas obtenidas de sangre periférica en pacientes con aterosclerosis obliterante grado IV, de Pinar del Río, atendidos en el período de 2009-2019. Métodos: se realizó un estudio descriptivo, longitudinal, con 296 pacientes que presentaban aterosclerosis obliterante grado IV durante en el período de 2009-2019. Se obtuvo el concentrado de células madres autólogas de sangre periférica. Las células se analizaron por citometría de flujo, donde mostraron una viabilidad celular del 99,3 %. Se les inyectó por vía intramuscular un concentrado de células madres con un número de células inyectadas de ocho, seis, diez. Las variables estudiadas fueron: índice de presión tobillo-brazo en reposo, distancia de claudicación libre de dolor, evaluación de la escala del dolor y criterio de amputación. Resultado: se observó alivio del dolor a las cuatro semanas y aumento de la distancia de claudicación libre de dolor. La angiografía post tratamiento mostró formación de vasos colaterales. Presentaron criterio de amputación 95 casos (32 %) se logró salvar la extremidad en 201 pacientes (68 %). El proceder realizado no se asoció con ninguna complicación. Conclusión: la aplicación de células madres autólogas de sangre periférica es segura y eficaz para el tratamiento de la aterosclerosis obliterante grado IV.

ABSTRACT Introduction: peripheral arterial disease of the lower limbs affects a high percentage of the world population; with autologous stem cells obtained from peripheral blood a greater synthesis of growth factors that induce angiogenesis is achieved. Objective: to describe the auto-transplantation of autologous stem cells obtained from peripheral blood in patients with grade IV atherosclerosis obliterans in Pinar del Rio treated during period 2009-2019. Methods: a descriptive, longitudinal study was carried out with 296 patients with grade IV atherosclerosis obliterans during the period 2009-2019. Autologous peripheral blood stem cell concentrate was obtained. The cells were analyzed by flow cytometry, where they showed a cell viability of 99,3 %. Stem cell concentrate was injected intramuscularly with a number of cells injected of eight, six and ten. The variables studied were ankle-brachial pressure index at rest, pain-free claudication distance, pain scale assessment and amputation criteria. Result: pain relief was observed at four weeks and increase in pain-free claudication distance. Post-treatment angiography showed collateral vessel formation. Amputation criteria were met in 95 cases (32 %) and the limb was saved in 201 patients (68 %). The procedure carried out was not associated with complications. Conclusion: the application of autologous peripheral blood stem cells is safe and effective for the treatment of grade IV atherosclerosis obliterans.

Hallazgos intraorales en pacientes de una población colombiana infectados con SARS-CoV-2: informe de casos / Intraoral findings in patients in a Colombian population infected with SARSCoV-2: series of case

Objetivo. Identificar y describir las lesiones orales encontradas en los pacientes con infección por SARS-CoV 2. Métodos. Serie de casos con descripción de 11 pacientes confirmados de infección por SARS-CoV-2 por hisopado nasofaríngeo o prueba serológica para confirmar la infección; con la presencia de manifestaciones intraorales de diferentes tipos. A todos los pacientes se les realizó teleconsulta por parte de un estomatólogo y se recopilaron los datos relevantes como edad, sexo, antecedentes de enfermedades preexistentes, tipo de lesión estomatológica presente, sitio y sintomatología, entre otros. Todos los pacientes firmaron un consentimiento informado. Resultados. De los 11 casos positivos para SARS-CoV-2, el 63,63% de los pacientes corresponden al sexo femenino (n=7) y 36,36% (n=4) sexo masculino. El 100% de los pacientes fueron diagnosticados por pruebas moleculares y serológicas; así, el 90,90% se diagnosticaron con PCR viral y 9,09% diagnosticado por prueba para antígeno. Las lesiones ulcerativas predominaron en el 54,54%; seguidas de pseudoplaca y eritema en 18,18% respectivamente. Las vesículas y costras se presentaron en el 9,09% respectivamente. El 72,72 (n=8) presentó ageusia y anosmia, y el 45,45 % (n=5) manifestaron comorbilidades como diabetes, hipertensión arterial e hipotiroidismo. Conclusiones. Esta enfermedad viral cursa con lesiones bucales y muchas veces es la primera e incluso la única manifestación que se presenta durante su curso, por eso es importante tener en cuenta e identificar estas lesiones y saber su relación con el manejo terapéutico, compromiso inmunológico o la propia enfermedad.

Objective. To identify and describe the oral lesions found in patients with SARS-CoV-2 infection. Methods. Series of cases with description of 11 patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab or serological test to confirm the infection; with the presence of intraoral manifestations of different types. All patients underwent tele-consultation by a stomatologist and relevant data such as age, sex, history of pre-existing diseases, type of stomatological lesion present, site and symptomatology, among others, were collected. All patients signed an informed consent form. Results. Of the 11 positive cases for SARS-CoV-2, 63.63% (n=7) of the patients were female and 36.36% (n=4) were male. All patients (100%) were diagnosed by molecular and serological tests, 90.90% were diagnosed by viral PCR and 9.09% were diagnosed by antigen test. Ulcerative lesions predominated in 54.54%; followed by pseudoplaque and erythema in 18.18% of patients, respectively. Vesicles and crusts were present in 9.09% respectively. Ageusia and anosmia were present in 72.72 (n=8), and 45.45% (n=5) of patients showed comorbidities such as diabetes, arterial hypertension and hypothyroidism. Conclusions. This viral disease presents with oral lesions and it is usually the first and even the only manifestation during its course. That is why it is important to take into account and identify these lesions, and know their relationship with the therapeutic management, immunological compromise or the disease itself.

Chaperone-Mediated Autophagy Controls Proteomic and Transcriptomic Pathways to Maintain Glioma Stem Cell Activity.

Chaperone-mediated autophagy (CMA) is a homeostatic process essential for the lysosomal degradation of a selected subset of the proteome. CMA activity directly depends on the levels of LAMP2A, a critical receptor for CMA substrate proteins at the lysosomal membrane. In glioblastoma (GBM), the most common and aggressive brain cancer in adulthood, high levels of LAMP2A in the tumor and tumor-associated pericytes have been linked to temozolomide resistance and tumor progression. However, the role of LAMP2A, and hence CMA, in any cancer stem cell type or in glioblastoma stem cells (GSC) remains unknown. In this work, we show that LAMP2A expression is enriched in patient-derived GSCs, and its depletion diminishes GSC-mediated tumorigenic activities. Conversely, overexpression of LAMP2A facilitates the acquisition of GSC properties. Proteomic and transcriptomic analysis of LAMP2A-depleted GSCs revealed reduced extracellular matrix interaction effectors in both analyses. Moreover, pathways related to mitochondrial metabolism and the immune system were differentially deregulated at the proteome level. Furthermore, clinical samples of GBM tissue presented overexpression of LAMP2, which correlated with advanced glioma grade and poor overall survival. In conclusion, we identified a novel role of CMA in directly regulating GSCs activity via multiple pathways at the proteome and transcriptome levels. SIGNIFICANCE: A receptor of chaperone-mediated autophagy regulates glioblastoma stem cells and may serve as a potential biomarker for advanced tumor grade and poor survival in this disease.