Exploring the Benefits of Nutritional and Chemical Characteristics of Touriga Nacional and Arinto Varieties (Vitis vinifera L.).

Environmental degradation leads to an unsustainable food system. In addition to this issue, the consumption of foods that improve people's health and well-being is recommended. One of the alternatives is undoubtedly the use of by-products of winemaking, namely in the form of grape pomace flour (GPF). To verify the benefits of using the Touriga Nacional and Arinto (Vitis vinifera L.) flour varieties, analytical determinations were made to identify and quantify different components. In terms of nutritional characterization, the Touriga Nacional GPF showed results that indicate better nutritional quality than the Arinto GPF. The Touriga Nacional and Arinto samples had protein contents of 10.13% and 8.38%, polyunsaturated fatty acids of 6.66% and 5.18%, soluble dietary fiber of 14.3% and 1.7%, and insoluble dietary fiber of 55.1% and 46.4%, respectively. The anthocyanins, proanthocyanidins, and flavonols presented in samples were detected by HPLC-DAD/ESI-MS. Atomic absorption spectrometry revealed elevated concentrations of certain elements in Touriga Nacional compared to Arinto, with the former showing higher levels of aluminum (130 mg/kg) and iron (146 mg/kg) against the latter's Al (120 mg/kg) and Fe (112 mg/kg) content. GPF could become a valuable ingredient due to its nutritional quality and high content of various polyphenols.

Real-World Outcome of Treatment with Single-Agent Ibrutinib in Italian Patients with Chronic Lymphocytic Leukemia: Final Results of the EVIdeNCE Study.

Real-world data in clinical practice are needed to confirm the efficacy and safety that ibrutinib has demonstrated in clinical trials of patients with chronic lymphocytic leukemia (CLL). We described the real-world persistence rate, patterns of use, and clinical outcomes in 309 patients with CLL receiving single-agent ibrutinib in first line (1L, n = 118), 2L (n = 127) and ≥3L (n = 64) in the prospective, real-world, Italian EVIdeNCE study. After a median follow-up of 23.9 months, 29.8% of patients discontinued ibrutinib (1L: 24.6%, 2L: 29.9%, ≥3L: 39.1%), mainly owing to adverse events (AEs)/toxicity (14.2%). The most common AEs leading to discontinuation were infections (1L, ≥3L) and cardiac events (2L). The 2-year retention rate was 70.2% in the whole cohort (1L: 75.4%, 2L: 70.1%, ≥3L: 60.9%). The 2-year PFS and OS were, respectively, 85.4% and 91.7% in 1L, 80.0% and 86.2% in 2L, and 70.1% and 80.0% in ≥3L. Cardiovascular conditions did not impact patients' clinical outcomes. The most common AEs were infections (30.7%), bleeding (12.9%), fatigue (10.0%), and neutropenia (9.7%), while grade 3-4 atrial fibrillation occurred in 3.9% of patients. No new safety signals were detected. These results strongly support ibrutinib as a valuable treatment option for CLL.

Therapeutic Potential in Wound Healing of Allogeneic Use of Equine Umbilical Cord Mesenchymal Stem Cells.

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.

Plasma sodium concentration in older patients as an indicator of severity in emergencies: Results from the Emergency Department and Elder Needs-16 study. / Estudio EDEN-16: sodio plasmático determinado a la llegada a urgencias como indicador de gravedad en pacientes ancianos.

OBJECTIVES: To study baseline factors associated with hypo- and hypernatremia in older patients attended in emergency departments (EDs) and explore the association between these dysnatremias and indicators of severity in an emergency. MATERIAL AND METHODS: We included patients attended in 52 Spanish hospital EDs aged 65 years or older during a designated week. All included patients had to have a plasma sodium concentration on record. Patients were distributed in 3 groups according to sodium levels: normal, 135-145 mmol/L; hyponatremia, 135 mmol/L; or hypernatremia > 145 mmol/L. We analyzed associations between sodium concentration and 24 variables (sociodemographic information, measures of comorbidity and baseline functional status, and ongoing treatment for hypo- or hypernatremia). Indicators of the severity in emergencies were need for hospitalization, in-hospital mortality, prolonged ED stay (> 12 hours) in discharged patients, and prolonged hospital stay (> 7 days) in admitted patients. We used restricted cubic spline curves to analyze the associations between sodium concentration and severity indicators, using 140 mmol/L as the reference. RESULTS: A total of 13 368 patients were included. Hyponatremia was diagnosed in 13.5% and hypernatremia in 2.9%. Hyponatremia was associated with age ($ 80 years), hypertension, diabetes mellitus, an active neoplasm, chronic liver disease, dementia, chemotherapy, and needing help to walk. Hypernatremia was associated with needing help to walk and dementia. The percentages of cases with severity indicators were as follows: hospital admission, 40.8%; in-hospital mortality, 4.3%; prolonged ED stay, 15.9%; and prolonged hospital stay, 49.8%. Odds ratios revealed associations between lower sodium concentration cut points in patients with hyponatremia and increasing need for hospitalization (130 mmol/L, 2.24 [IC 95%, 2.00-2.52]; 120 mmol/L, 4.13 [3.08-5.56]; and 110 mmol/L, 7.61 [4.53-12.8]); risk for in-hospital death (130 mmol/L, 3.07 [2.40-3.92]; 120 mmol/L, 6.34 [4.22- 9.53]; and 110 mmol/L, 13.1 [6.53-26.3]); and risk for prolonged ED stay (130 mmol/L, 1.59 [1.30-1.95]; 120 mmol/L, 2.77 [1.69-4.56]; and 110 mmol/L, 4.83 [2.03-11.5]). Higher sodium levels in patients with hypernatremia were associated with increasing need for hospitalization (150 mmol/L, 1.94 [1.61-2.34]; 160 mmol/L, 4.45 [2.88-6.87]; 170 mmol/L, 10.2 [5.1-20.3]; and 180 mmol/L, 23.3 [9.03-60.3]); risk for in-hospital death (150 mmol/L, 2.77 [2.16-3.55]; 160 mmol/L, 6.33 [4.11-9.75]; 170 mmol/L, 14.5 [7.45-28.1]; and 180 mmol/L, 33.1 [13.3-82.3]); and risk for prolonged ED stay (150 mmol/L, 2.03 [1.48-2.79]; 160 mmol/L, 4.23 [2.03-8.84]; 170 mmol/L, 8.83 [2.74-28.4]; and 180 mmol/L, 18.4 [3.69-91.7]). We found no association between either type of dysnatremia and prolonged hospital stay. CONCLUSION: Measurement of sodium plasma concentration in older patients in the ED can identify hypo- and hypernatremia, which are associated with higher risk for hospitalization, death, and prolonged ED stays regardless of the condition that gave rise to the dysnatremia.

OBJETIVO: Estudiar los factores basales asociados a hiponatremia e hipernatremia en pacientes mayores atendidos en urgencias y la relación de estas disnatremias con eventos indicadores de gravedad. METODO: Se incluyeron durante una semana a todos los pacientes atendidos en 52 servicios de urgencias hospitalarios españoles de edad $ 65 años con determinación de sodio plasmático. Se formaron tres grupos: sodio normal (135-145 mmol/L), hiponatremia ( 135 mmol/L) e hipernatremia (> 145 mmol/L). Se investigó la relación de 24 factores sociodemográficos, de comorbilidad, estado funcional basal y tratamiento crónico con hipo e hipernatremia. Como eventos de gravedad se recogieron necesidad de hospitalización, mortalidad intrahospitalaria, estancia prolongada en urgencias (> 12 horas) en dados de alta y hospitalización prolongada (> 7 días) en hospitalizados, y se analizó su relación con la concentración de sodio mediante curvas spline cúbicas restringidas ajustadas, tomando el valor 140 mmol/L como referencia. RESULTADOS: Se incluyeron 13.368 pacientes (13,5% hiponatremia, 2,9% hipernatremia). La hiponatremia se asoció a edad $ 80 años, hipertensión arterial, diabetes mellitus, neoplasia activa, hepatopatía crónica, demencia, tratamiento con quimioterápicos y ayuda para la deambulación, y la hipernatremia a dependencia, necesidad de ayuda para deambular y demencia. La hospitalización fue del 40,8%, la mortalidad intrahospitalaria del 4,3%, la estancia prolongada en urgencias del 15,9% y la hospitalización prolongada del 49,8%. A mayor hiponatremia, mayor necesidad de hospitalización (sodio 130 mmol/L: OR:2,24; IC 95%: 2,00-2,52; 120 mmol/L: 4,13, 3,08-5,56; 110 mmol/L: 7,61, 4,53-12,8), mortalidad intrahospitalaria (130 mmol/L: 3,07, 2,40-3,92; 120 mmol/L: 6,34, 4,22-9,53; 110 mmol/L: 13,1, 6,53-26,3) y estancia prolongada en urgencias (130 mmol/L: 1,59, 1,30-1,95; 120 mmol/L: 2,77, 1,69-4,56; 110 mmol/L: 4,83, 2,03-11,5), y a mayor hipernatremia mayor necesidad de hospitalización (150 mmol/L: 1,94, 1,61-2,34; 160 mmol/L: 4,45, 2,88-6,87; 170 mmol/L: 10,2, 5,1-20,3; 180 mmol/L: 23,3, 9,03-60,3), mortalidad intrahospitalaria (150 mmol/L: 2,77, 2,16-3,55; 160 mmol/L: 6,33, 4,11-9,75; 170 mmol/L: 14,5, 7,45-28,1; 180 mmol/L: 33,1, 13,3-82,3) y estancia prolongada en urgencias (150 mmol/L: 2,03, 1,48-2,79; 160 mmol/L: 4,23, 2,03-8,84; 170 mmol/L: 8,83, 2,74-28,4; 180 mmol/L: 18,4, 3,69-91,7). No hubo asociación entre estas disnatremias y hospitalización prolongada. CONCLUSIONES: El sodio plasmático determinado en urgencias en pacientes mayores permite identificar hiponatremias e hipernatremias, las cuales se asocian a un riesgo incrementado de hospitalización, mortalidad y estancia prolongada en urgencias independientemente de la causa que haya generado la disnatremia.

Púrpura de Schönlein Henoch en paciente adulto

RESUMEN La púrpura de Schönlein-Henoch es una vasculitis por fragmentación de leucocitos inmunomediada que afecta a pequeños vasos sanguíneos. Los cuatro componentes clínicos esenciales son púrpuras, dolor abdominal, artralgia y afectación renal. El caso trata de una mujer de 50 años que ingresa por dolor abdominal y hematoquecia de 72 horas de evolución, posterior a laparotomía exploratoria. Al examen físico presenta lesiones purpúricas en tronco y extremidades inferiores de 2 meses de aparición. En paraclínicos se observa hemograma con plaquetas normales, proteínas en orina 500 mg/dL, proteinuria 2,4 g/24 hs. Ante sospecha de vasculitis con plausible inclusión cutáneo-renal, se pide anticuerpos antinucleares, ANCA y se realiza biopsia cutánea evidenciándose una vasculitis neutrofílica necrotizante de pequeños vasos. En la biopsia renal se observa en inmunofluorescencia directa depósito de IgA, C3 positivo. En relación clínica de la proteinuria y compromiso cutáneo junto con la confirmación de biopsia renal se concluye en diagnóstico de púrpura de Schönlein Henoch. El interés de este caso radica en la inconsistencia de esta patología en los adultos, a pesar de que bien podría ser de una gravedad más notable dado que existe un mayor peligro de falla renal persistente.

ABSTRACT Schönlein-Henoch purpura is an immune-mediated leukocyte fragmentation vasculitis that affects small blood vessels. The four essential clinical components are purpura, abdominal pain, arthralgia, and renal involvement. This case concerns a 50-year-old woman who is admitted due to abdominal pain and hematochezia of 72 hours of evolution, after an exploratory laparotomy. On physical examination, she presents purpuric lesions on the trunk and lower extremities of 2 months of appearance. In paraclinical tests, a blood count with normal platelets, urine protein 500 mg/dL, and proteinuria 2.4 g/24 hours are observed. Suspecting vasculitis with plausible cutaneous-renal inclusion, antinuclear antibodies and ANCA are requested, and a skin biopsy is performed, showing necrotizing neutrophilic vasculitis of small vessels. In the renal biopsy, IgA deposit, C3 positive is observed in the direct immunofluorescence. In the clinical relationship of proteinuria and skin involvement together with the confirmation of renal biopsy, the diagnosis of Schönlein-Henoch purpura is concluded. The interest of this case lies in the inconsistency of this pathology in adults, despite the fact that it could be more serious given that there is a greater risk of persistent renal failure.

In vitro antimicrobial activity of Douro wines against clinical Helicobacter pylori strains / strains121In vitro antimicrobial activity of Douro wines against clinical helicobacter pylori strains / Actividad antimicrobiana in vitro de los vinos del Duero sobre cepas clínicas de Helicobacter pylori

Abstract Aim. In vitro antimicrobial activities of seven wines (5 reds and 2 whites) from the Douro region (Iberian Peninsule) against eleven clinical strains of Helicobacter pylori were evaluated. Methods. The disk diffusion method, using Columbia Agar supplemented with horse blood (CAB), were used to determine the antimicrobial properties of some wine components against H. pylori strains. Potential interactions of antioxidants contained in the wines and two antimicrobials (amoxicillin and metronidazole) were studied by the disk diffusion method. Results. All the tested strains showed growth in CAB supplemented with 9% of the tested wines but none of them grew in media supplemented with 45% and 67.5% of wine. Similarly, all the tested strains grew in media with the concentration of proanthocyanidins present in the different types of the studied wines. The Minimal Inhibitory Concentration (MIC) values of the wine antioxidant components tested (benzoic acid, catechin, quercetin, and resveratrol) indicate that resveratrol was the most powerful inhibitory substance against H. pylori. An effect of potentiation between amoxicillin and metronidazole and the antioxidants tested was also established. The interaction of amoxicillin and resveratrol or metronidazole and catechin increased the antimicrobial activity against H. pylori. Conclusions. The results obtained suggested a potential role of resveratrol as a chemopreventive agent for H. pylori infection.

Resumen Objetivo. Se evaluó las actividades antimicrobianas in vitro de siete vinos (5 tintos y 2 blancos) de la región del Duero (Peninsula Ibérica) frente a once cepas de Helicobacter pylori de origen clínico. Métodos. Para determinar las propiedades antimicrobianas de algunos componentes del vino sobre las cepas de H. pylori se utilizaron las técnicas de difusión en disco en placas de agar Columbia suplementado con sangre de caballo (CAB). La potential interacción entre las sustancias antioxidantes presentes en los vinos y dos antimicrobianos (amoxicilina y metronidazol) se determinó usando la técnica de difusión en disco. Resultados. Todas las cepas ensayadas mostraron crecimiento en CAB suplementado con el 9% de los vinos analizados, pero no se obtuvo crecimiento de ninguna de las cepas en medios suplementados con el 45% y el 67,5% de vino. Asimismo, todas las cepas ensayadas crecieron en medios con la concentración de proantocianidinas presentes en los diferentes tipos de vinos estudiados. Los valores de concentración mínima inhibitoria (CMI) de los componentes antioxidantes de los vinos ensayados (ácido benzoico, catequina, quercetina y resveratrol) indican que el resveratrol fue la sustancia más potente en la inhibición del crecimiento de H. pylori. También se estableció un efecto de potenciación entre amoxicilina y metronidazol y los antioxidantes ensayados. Las interacciones amoxicilina + resveratrol y metronidazol + catequina aumentaron la actividad antimicrobiana contra H. pylori. Conclusiones. Los resultados obtenidos sugieren un papel potencial del resveratrol como agente quimiopreventivo de la infección por H. pylori.

HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy.

Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G - cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.

Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells.

In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton's jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR-. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.

Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.

PURPOSE: Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosis. METHODS: We conducted target panel genetic screening using single-molecule molecular inversion probes sequencing to assess the frequency of mutations in known hypopituitarism genes and new candidates in Argentina. We captured genomic deoxyribonucleic acid from 170 pediatric patients with CH, either alone or with other abnormalities. We performed promoter activation assays to test the functional effects of patient variants in LHX3 and LHX4. RESULTS: We found variants classified as pathogenic, likely pathogenic, or with uncertain significance in 15.3% of cases. These variants were identified in known CH causative genes (LHX3, LHX4, GLI2, OTX2, HESX1), in less frequently reported genes (FOXA2, BMP4, FGFR1, PROKR2, PNPLA6) and in new candidate genes (BMP2, HMGA2, HNF1A, NKX2-1). CONCLUSION: In this work, we report the prevalence of mutations in known CH genes in Argentina and provide evidence for new candidate genes. We show that CH is a genetically heterogeneous disease with high phenotypic variation and incomplete penetrance, and our results support the need for further gene discovery for CH. Identifying population-specific pathogenic variants will improve the capacity of genetic data to predict eventual clinical outcomes.

Single-Pass Mikrokeratome and Anterior Chamber Pressurizer for the Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty Graft Preparation.

PURPOSE: To compare the reliability of microkeratome dissection with the anterior chamber pressurizer (ACP) system versus conventional pressurization for ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK) graft preparation. METHODS: A retrospective review of a consecutive series of dissected donor corneas processed at Pavia Eye Bank for UT-DSAEK surgery was performed. Grafts were prepared through single-pass microkeratome dissection with artificial anterior chamber internal pressure regulation through either ACP or the conventional method using a water column with tube clamp. The target central graft thickness (CGT) was ≤100 µm. Cutting predictability was determined as the difference between the microkeratome head size and the thickness actually removed. Graft regularity was investigated as central-to-peripheral thickness increase, central-to-peripheral (CP) ratio, and graft thickness uniformity. Thickness was measured with anterior segment optical coherence tomography (horizontal and vertical meridians). RESULTS: Of the 265 UT-DSAEK grafts, ACP achieved the target "CGT ≤ 100 µm" in 87 of 120 (72.5%), whereas the conventional technique achieved the same in 85 of 145 (58.6%) (P = 0.018). ACP predictability was -3.9 µm (SD: 2.3), whereas predictability of the conventional technique was -54.6 µm (SD: 3.7) (P < 0.001). Thickness increased similarly (P = 0.212); CP ratio was better with ACP for only 2 mm diameter (P = 0.001); graft thickness uniformity was comparable (P > 0.05). CONCLUSIONS: Compared with conventional pressurization, ACP improved microkeratome-assisted preparation reliability of UT-DSAEK grafts, achieving CGT ≤ 100 µm with significantly higher frequency (P = 0.018) and predictability (P < 0.001). ACP improved CP ratio only at 2 mm (P = 0.001); for other graft thickness, the 2 methods proved equivalent.

The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. METHODS: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo" Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. RESULTS: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. CONCLUSIONS: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.

Polyphasic studies of new species of Diaporthe from native forest in Chile, with descriptions of Diaporthe araucanorum sp. nov., Diaporthe foikelawen sp. nov. and Diaporthe patagonica sp. nov.

During a survey of fungi in native forests in Chile, several unidentified isolates of Diaporthe were collected from different hosts. The isolates were characterized based on DNA comparisons, morphology, culture characteristics and host affiliation, in accordance with previous descriptions. Phylogenetic analysis of the ITS region, combined with partial tub2 and tef1 genes, showed that the isolates formed three distinct groups representing three new taxa. The three new species of Diaporthe, Diaporthe araucanorum on Araucaria araucana, Diaporthe foikelawen on Drimys winteri and Diaporthe patagonica on Aristotelia chilensis are described and illustrated in the present study.

Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets.

Clear cell renal cell carcinoma (ccRCC) constitutes the most common renal cell carcinoma subtype and has long been recognized as an immunogenic cancer. As such, significant attention has been directed toward optimizing immune-checkpoints (IC)-based therapies. Despite proven benefits, a substantial number of patients remain unresponsive to treatment, suggesting that yet unreported, immunosuppressive mechanisms coexist within tumors and their microenvironment. Here, we comprehensively analyzed and ranked forty-four immune-checkpoints expressed in ccRCC on the basis of in-depth analysis of RNAseq data collected from the TCGA database and advanced statistical methods designed to obtain the group of checkpoints that best discriminates tumor from healthy tissues. Immunohistochemistry and flow cytometry confirmed and enlarged the bioinformatics results. In particular, by using the recursive feature elimination method, we show that HLA-G, B7H3, PDL-1 and ILT2 are the most relevant genes that characterize ccRCC. Notably, ILT2 expression was detected for the first time on tumor cells. The levels of other ligand-receptor pairs such as CD70:CD27; 4-1BB:4-1BBL; CD40:CD40L; CD86:CTLA4; MHC-II:Lag3; CD200:CD200R; CD244:CD48 were also found highly expressed in tumors compared to adjacent non-tumor tissues. Collectively, our approach provides a comprehensible classification of forty-four IC expressed in ccRCC, some of which were never reported before to be co-expressed in ccRCC. In addition, the algorithms used allowed identifying the most relevant group that best discriminates tumor from healthy tissues. The data can potentially assist on the choice of valuable immune-therapy targets which hold potential for the development of more effective anti-tumor treatments.

Intervención educativa en salud comunitaria para el empoderamiento de jefas de hogar en un sector económicamente vulnerable de la ciudad de Santiago de Chile / Health community educational intervention to empowerment female heads of households in an economic disadvantage community in Santiago Chile

OBJETIVO: contribuir al empoderamiento de las mujeres jefas de hogar pertenecientes a una comunidad de un sector económicamente vulnerable de la ciudad de Santiago, por medio de la entrega de herramientas y habilidades en salud. Muestra: 13 mujeres, entre 22 y 55 años. METODOLOGÍA: Intervención educativa basada en el Modelo 'Comunidad como Socio' de Anderson y McFarlane de Enfermería y el Modelo de Educación para Adultos de Jane Vella. Se respondió una encuesta anónima para recopilar información. El diagnóstico participativo permitió identificar temas a tratar: control de signos vitales y su aplicabilidad, y atención de primeros auxilios. RESULTADOS: Se aportó al conocimiento del manejo de cuidados básicos en salud (Signos Vitales, Primeros Auxilios y Hábitos de Vida Saludable) aplicados a su autocuidado y al de sus familias. Se practicó lo aprendido en un escenario simulado. CONCLUSIÓN: Se identificaron fortalezas, como motivación por el aprendizaje y buena recepción de las metodologías participativas. La intervención contribuyó al empoderamiento de las participantes mediante el aprendizaje de contenidos, otorgando seguridad para enfrentar situaciones de emergencia en su vida cotidiana.

OBJECTIVE: Contribute the empowerment of female heads of household belonging to a community of an economically vulnerable sector of the city of Santiago, through the delivery of tools and skills in health. Sample: 13 women, between 22 and 55 years old. METHODOLOGY: Educational intervention based on the "Community as a Partner" Model of Anderson and McFarlane of Nursing and the Adult Education Model of Jane Vella. A survey was answered anonymously to collect information. The participatory diagnosis allowed identifications of thetopics concerned including: control of vital signs and its applications and first aid attention demonstrated practically in the sessions. RESULTS: Contributions were made to the knowledge regarding the management of basic care in health (Vital Signs, First Aid and Habits of Healthy Living) applied to self-care of patients and their respective families. In a simulated scenario, participants in the survey demonstrated that they practiced what they had learned. CONCLUSION: Strengths such as motivation for learning and positive response to participative methodologies were identified. Additionally, the intervention contributed to the empowerment of the participants through the learning of contents and development of confidence to confront emergency situations in every day life.

Carga de neumonía en adultos hospitalizados / Pneumonia loading in hospitalized adults / Pneumonia carregando em adultos hospitalizados

La neumonía adquirida en la comunidad en adultos, es un importante problema de salud pública. En América Latina son muy escasas las publicaciones que documenten su incidencia. Esta comunicación breve proporciona datos preliminares sobre la incidencia (105 persona/año) de neumonías en adultos hospitalizados. La base de datos de una institución médica privada de Uruguay, posibilitó la estimación de la incidencia de esa patología, antes de la implementación de la vacuna conjugada neumocóccica (VCN) en la infancia y luego de su aplicación. En 1.688 pacientes con neumonía los mayores de 64 años predominaron y su incidencia fue de 1.938 en el período prevacunación, descendiendo significativamente a 1.365 luego de la VCN. A pesar de la posible protección indirecta de la vacunación, la información presentada alerta sobre la persistencia de morbimortalidad por neumonía en adultos mayores.

Pneumonia in adults poses severe health risks, but data on its burden still lacks in Latin American countries including Uruguay. To fill this gap preliminary information on hospitalized pneumonia incidence in adults was analyzed. A data base from a private medical institution enabled to estimate, pre and post pneumococcal conjugate vaccine incidences (105 person/year), by age groups. Out of 1 688 adults hospitalized due to pneumonia, the group aged >64 yers predominated. For the same age group, a significant difference (1.938 vs. 1.365) was observed on incidences before and after conjugate vaccine application in children. Although more robust information on adult pneumonia hospitalizations are required to confirm indirect vaccine effect, these data alert on pneumonia persistence which requires preventive measures.

A pneumonia adquirida na comunidade em adultos é um grande problema de saúde pública. Na América Latina existem muito poucas publicações que documentam sua incidência. Esta breve comunicação fornece dados preliminares sobre a incidência (105 pessoas / ano) de pneumonias em adultos hospitalizados. O banco de dados de uma instituição médica privada no Uruguai possibilitou estimar a incidência dessa patologia, antes da implementação da vacina conjugada pneumocócica (VCN) na infância e após sua aplicação. Em 1.688 pacientes com pneumonia, aqueles com mais de 64 anos de idade predominaram e sua incidência foi de 1.938 no período de pré-vacinação, descendo significativamente para 1.365 após a VCN. Apesar da possível proteção indireta da vacinação, as informações apresentadas alertam sobre a persistência da morbimortalidade por pneumonia em idosos.

Effects of Liquid Medium and Ablation Wavelength on the Properties of Cadmium Sulfide Nanoparticles Formed by Pulsed-Laser Ablation.

Pulsed-laser ablation in liquid (PLAL) is a green synthesis technique to obtain semiconductor nanomaterials in colloidal form. Herein, cadmium sulfide (CdS) nanoparticles were synthesized by the pulsed-laser ablation of a CdS target in different liquid media by using λ=532 and 1064 nm outputs from a pulsed (10 ns, 10 Hz) Nd:YAG laser at different ablation fluence values. The morphology, structure, crystalline phase, elemental composition, optical, and luminescent properties of CdS nanomaterials were analyzed by using transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV/Vis absorption spectroscopy, and fluorescence spectroscopy. By changing the liquid medium and ablation wavelength, CdS nanoparticles with different morphology and size were formed, as demonstrated by using TEM analysis. The crystallinity and chemical states of the ablation products were confirmed by using XRD and XPS analyses. The optical bandgap of the CdS nanoparticles was dependent on the ablation wavelength and the fluence. These nanocolloids presented different green emissions, which implied the presence of several emission centers. CdS nanocolloids in distilled water catalyzed the photocatalytic decay of methylene blue dye under light irradiation from a solar simulator.

Desarrollo sustentable desde el enfoque de autocuidado: Un aporte a la práctica de enfermería / Sustainable development from a self-care approach: A contribution to a nursing practice

La relación entre salud y ambiente no es una temática reciente, ya en el año 1974 la Agencia de Salud Pública de Canadá establece en su informe Lalonde los factores claves que parecían determinar el estado de salud de los individuos, identificando así el estilo de vida, el ambiente, la biología humana y los servicios de salud. En el año 2012, se realiza la Conferencia de las Naciones Unidas sobre el desarrollo sostenible, que en su documento final "El futuro que queremos" señala "la salud es una condición previa, un resultado y un indicador de las tres dimensiones del desarrollo sostenible", es decir, las dimensiones social, ambiental y económica. El impacto que tienen los cambios en el ecosistema sobre la salud de la población está en directa relación en cómo el ser humano se relaciona con su entorno y utiliza los recursos disponibles brindándoles la oportunidad de renovarse a través de ciclos naturales. Es así como desde el paradigma de sustentabilidad se propone observar, comprender e intervenir en nuestro entorno teniendo presente que todos los sistemas, tanto naturales como los creados por el hombre, interactúan e influyen entre sí. A través de dos de los requisitos de Autocuidado de la salud como son normalidad y peligros para la vida, planteados por Dorothea Orem se analizará cómo los cambios en nuestro ecosistema pueden repercutir en el continuo salud-enfermedad de las personas.

The relationship between health and environment is not recent-In 1974 the Public Health Agency of Canada established in its Lalonde report, the key factors that seemed to determine the health condition of individuals, thus identifying the lifestyle, the environment, human biology and health services.In 2012, the UN Conference on Sustainable Development takes place and in its final document "The future we want" says: "health is a precondition, an outcome and an indicator of the three dimensions of sustainable development" -that is -the social, environmental and economic dimensions. The impact of changes in the ecosystem about the health of the population is directly related to how human beings interact with their environment and use available resources giving them the opportunity to renew it through natural cycles. Thereby, since the sustainability paradigm is proposed to observe, understand and intervene in our environment bearing in mind that all systems, both natural and manmade, interact and influence each other. Through two of the requirements of self-care such as normality and hazards to life, raised by Dorothea Orem will analyze how changes in our ecosystem can affect the health-disease continuum of individuals.

Regeneração óssea guiada no tratamento de peri-implantite: dois anos de acompanhamento clínico / Guided bone regeneration in the treatment of peri-implantitis: 2 years of clinical follow-up

A peri-implantite é caracterizada pelo processo inflamatório ao redor de um implante, que inclui inflamação do tecido mole e perda progressiva de suporte ósseo. O foco do seu tratamento está no controle da infecção bacteriana, através da eliminação do biofilme da superfície do implante e, quando possível, na regeneração do osso perdido. Contudo, atualmente não existe evidência suficiente na literatura para indicar qual abordagem terapêutica é superior no tratamento da peri-implantite a longo prazo. Dessa forma, o objetivo do presente relato de caso clínico foi reportar os resultados a longo prazo do tratamento de um caso de peri-implantite, com a combinação de acesso cirúrgico para descontaminação da superfície do implante, uso adjunto de solução de tetraciclina (50 mg/ml) e procedimento de regeneração óssea guiada, utilizando enxerto xenógeno e membrana reabsorvível de colágeno. Aos dois anos de acompanhamento pós-operatório, observou-se uma melhora clínica significativa, com redução da profundidade de sondagem, ganho de inserção clínica e preenchimento ósseo radiográfico do defeito peri-implantar. Pôde-se observar que o acesso cirúrgico associado à regeneração óssea guiada é uma alternativa viável para o tratamento de lesões de peri-implantite.

Peri-implantitis is an inflammatory process around an implant, which includes soft tissue inflammation and progressive bone loss. Treatment aims to control the bacterial infection through elimination of the established biofilm from the implant surface, and if possible, the regeneration of the lost bone. However, currently there is not sufficient evidence in the literature supporting which therapeutic approach is most suitable for the treatment of peri-implantits at long-term follow-up. Thus, the aim of this case demonstrate was to report the results of a peri-implantitis treatment at long-term follow-up, with the combination of surgical access for decontamination of the implant surface, with adjunctive use of tetracycline solution (50 mg/ml) and guided bone regeneration procedure using xenogeneic graft and resorbable collagen membrane. A significant clinical improvement was observed at 2 years of follow-up, with reduced probing depth, clinical attachment gain and radiographic bone fill in the peri-implant defect. It can be concluded that the surgical access associated with guided bone regeneration is a viable option for the treatment of peri-implant lesions

[Screening of pulmonary hypertension in a Spanish cohort of patients with systemic sclerosis]. / Cribado de hipertensión pulmonar en una cohorte española de pacientes con esclerosis sistémica.

BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc. PATIENTS AND METHOD: PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE>35 mmHg were evaluated per protocol to confirm diagnosis and type of PH. RESULTS: PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P<.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19). CONCLUSIONS: Prevalence of PAH in SSc was high and supports the implementation of a regular screening program.

Influence of the STAT3 genetic variants in the susceptibility to psoriatic arthritis and Behcet's disease.

OBJECTIVE: Signal-transducer and activator of transcription protein 3 (STAT3) gene encodes a transducer and transcription factor that plays an important role in many cellular processes such as cell growth, apoptosis and immune response. Several STAT3 genetic variants have been associated to different autoimmune diseases. Our aim was to reveal the possible STAT3 influence in other immune-mediated diseases such as psoriatic arthritis (PsA) and Behcet disease (BD). METHODS: The STAT3 rs744166 and rs2293152 polymorphisms were genotyped using predesigned TaqMan® assays in a total of 335 PsA patients, 217 BD patients, and 1844 ethnically matched healthy controls of Spanish Caucasian origin. RESULTS: A statistically significant association of the STAT3 rs744166(∗)G allele with PsA was observed (P-value=1.36×10(-3), OR 1.35). The detected effect was more evident when the rs744166(∗)GG homozygote frequencies were compared between PsA patients and controls (genotype P-value=9.77×10(-5), OR 1.82). In contrast, the allele and genotypic distributions of rs744166 polymorphism showed no significant differences between patients with BD and control subjects (allelic P-value=0.80, OR 1.03). Additionally, no evidence of association was detected between the rs2293152 genetic variant and both studied diseases. CONCLUSION: Our results suggest for the first time that the STAT3 gene might be involved in PsA but not in Behcet's disease predisposition.