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Background: The risk of Cardiovascular (CV) events is higher in HIV-infected patients (HIV+) compared to HIV-uninfected persons (HIV−). Large artery stiffness, a well-documented predictor of adverse CV prognosis, may mediate this enhanced risk. It is usually assessed by measuring aortic Pulse Wave Velocity (aPWV). Studies examining arterial stiffness in HIV+ yielded inconsistent results. We performed a meta-analysis with the aim to evaluate the association of HIV infection and its therapy [Antiretroviral Therapy (ART)] with aPWV. Design and Method: The Standardized Mean Difference (SMD) and corresponding 95% confidence intervals were calculated for aPWV in different comparison groups. Statistical heterogeneity, assessed by Q-test and I2 statistic, was observed in all these comparisons. Therefore, random effects model was implemented. Results: In a total of 12 studies, naive HIV+ (n = 547) showed increased aPWV compared to HIV− (n = 864): SMD = 0.333 (0.125–0.542), p < 0.002. A total of 22 studies were identified comparing HIV+ treated with ART (n = 3348) to HIV− (n = 2547) showing higher values of aPWV in the former than in latter: SMD = 0.391 (0.225–0.556), p < 0.001. In 10 studies, HIV+ treated with ART (n = 761) exhibited greater aPWV values than those of naive HIV+ (n = 457): SMD = 0.262 (0.006–0.518), p = 0.045. Conclusion: Our meta-analysis seems to suggest that HIV infection “per se” and ART may impair aortic distensibility. However, interpretation of our results needs caution due to between-study heterogeneity and some potential publication biases.

We report three critically ill pediatric patients (aged 6–10 years), presenting with features of multisystem inflammatory syndrome in children (MIS-C) from April 4 to May 10, 2020, to a tertiary-care center in New Jersey, United States. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were previously healthy. Clinical presentations were similar with fever, abdominal pain, gastrointestinal complaints, and/or rash. One patient had altered mental status with cerebrospinal fluid (CSF) findings consistent with aseptic meningitis. Laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin in all patients. All had low albumin levels. Evaluation for other infectious etiologies was negative. All of the patients were critically ill, requiring admission to the intensive care unit. All had circulatory shock and needed inotropes. Two patients had respiratory failure requiring advanced respiratory support and one had cardiac dysfunction. All patients received steroids, and two received intravenous immunoglobulin (IVIG). One patient received tocilizumab. None of the children died. MIS-C is a recently recognized pediatric illness spectrum in association with SARS-CoV-2 infection, and clinical characterization is essential for understanding disease mechanisms to inform clinical practice.

Enteritis as the only manifestation of novel coronavirus disease 2019 (COVID-19) in adolescents without features of multisystem inflammatory syndrome in children (MIS-C) or a prior history of inflammatory bowel disease (IBD) has not been described. We report two adolescent patients (a 14-year-old male and a 20-year-old pregnant female) presenting to tertiary-care centers in the United States with severe enteritis as the only manifestation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patients were hospitalized with acute abdominal pain and gastrointestinal (GI) bleeding, with no evidence of MIS-C, and were previously healthy with no history of IBD. The patients’ nasopharyngeal swabs were positive for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR), and testing for other infectious etiologies was negative. Both patients received intravenous corticosteroids and recovered without short-term complications. None of the patients died. This report highlights the need for keeping a high index of suspicion for SARS-CoV-2 infection in adolescents presenting solely with gastrointestinal manifestations, in the absence of respiratory symptoms or multisystem involvement, for prompt recognition and timely management.

Bone marrow (BM) is the major target organ for neuroblastoma (NB) metastasis and its involvement is associated with poor outcome. Yet, the mechanism by which NB cells invade BM is largely unknown. Tumour microenvironment represents a key element in tumour progression and mesenchymal stromal cells (MSCs) have been recognized as a fundamental part of the associated tumour stroma. Here, we show that BM-MSCs isolated from NB patients with BM involvement exhibit a greater osteogenic potential than MSCs from non-infiltrated BM. We show that BM metastasis-derived NB-cell lines secrete higher levels of exosomal miR-375, which promotes osteogenic differentiation in MSCs. Of note, clinical data demonstrate that high level of miR-375 correlates with BM metastasis in NB patients. Our findings suggest, indeed, a potential role for exosomal miR-375 in determining a favourable microenvironment in BM to promote metastatic progression. MiR-375 may, thus, represent a novel biomarker and a potential target for NB patients with BM involvement.

Abstract Background Clinical feedback is an important part of residency training, yet literature suggests this complex interaction is not completely understood. In particular, little is known about what resident versus attending physicians expect as feedback. This study investigates this gap in knowledge by examining differences in interactions that residents and attendings view as feedback. Methods Surveys containing sample clinical feedback scenarios were distributed to residents and attending physicians in emergency medicine and general surgery at a large academic medical center. Respondents were asked to decide whether useful feedback was provided in each scenario, and responses were compared between the two groups. Continuous features were summarized with medians, interquartile ranges (IQRs), and ranges; categorical features were summarized with frequency counts and percentages. Comparisons of features between residents and attendings were evaluated using Wilcoxon rank sum, chi-square, and Fisher exact tests. Statistical analyses were performed using version 9.4 of the SAS software package (SAS Institute, Inc.; Cary, NC). All tests were two-sided and p-values

O Queijo Artesanal Serrano é um produto nativo do sul do Brasil, produzido por mão de obra familiar a partir do leite cru, e que vem buscando a obtenção da sua indicação geográfica. Muitas das características que particularizam os tipos de queijo são dadas pela sua micobiota natural. O objetivo deste estudo foi determinar as espécies fúngicas presentes em 20 amostras de Queijo Artesanal Serrano de quatro períodos de maturação (14, 21, 28 e 35 dias), produzidos em outubro de 2017, em Santa Catarina. A identificação dos bolores foi feita por chaves de identificação e das leveduras por MALDI-TOF. Os bolores foram isolados em 28 das 80 amostras e com espécies variáveis, sendo algumas contaminantes. Por outro lado, as leveduras foram detectadas em todas as amostras, com alguns gêneros mais frequentes, principalmente o Kluyveromyces lactis, presente em 27 amostras, e algumas espécies de Candida spp. As espécies identificadas já foram isoladas em outros queijos artesanais brasileiros, produzido em locais com características de clima e relevo semelhantes ao do Queijo Artesanal Serrano.

O Queijo Artesanal Serrano é um produto tradicional do sul do Brasil, produzido pela agricultura familiar a partir do leite cru. O crescimento do consumo deste queijo requer atenção quanto a sua qualidade, visto que as únicas medidas de controle deste produto são as boas práticas de fabricação e a maturação. O objetivo desse trabalho foi avaliar alguns parâmetros de contaminação do Queijo Artesanal Serrano ao longo de 4 períodos de maturação (14, 21, 28 e 35 dias), como a contagem fúngica total, a quantificação de aflatoxina M1 e sujidades leves. A eficácia do período de maturação em relação à perda de água foi avaliada pela determinação da umidade e atividade de água. A contagem fúngica e a atividade de água (aw) não sofreram variação ao longo dos períodos de maturação empregados, com médias entre 4 - 7 log UFC g-1 e 0,97 - 0,98, respectivamente. A umidade foi diferente apenas entre os períodos de 14 e 21 dias de maturação, mas ainda assim os valores médios se mantiveram entre 40,39 e 43,66%, classificando o queijo como de massa semidura. A AFM1 foi detectada em apenas uma propriedade, em todos os períodos, mas em valores abaixo do estabelecido na legislação brasileira. As sujidades estavam presentes em 100% das amostras analisadas, com uma elevada prevalência de fibras sintéticas, além da presença de insetos e pelos. Os queijos analisados apresentaram segurança para o consumo em relação à quantificação dos fungos e à aflatoxina M1, porém as sujidades foram identificadas em número acima do permitido pela legislação, ainda que não tenha alterado a contagem dos microrganismos analisados.

Abstract Background The Intratumoral Microvessel Density (IMVD) is commonly used to quantify tumoral vascularization and is usually assessed by pan-endothelial markers, such as CD31. Endoglin (CD105) is a protein predominantly expressed in proliferating endothelium and the IMVD determined by this marker measures specifically the neovascularization. In this study, we investigated the CD105 expression in pediatric rhabdomyosarcoma and assessed the neovascularization by using the angiogenic ratio IMVD-CD105 to IMVD-CD31. Methods Paraffin-embedded archival tumor specimens were selected from 65 pediatric patients affected by rhabdomyosarcoma. The expression levels of CD105, CD31 and Vascular Endothelial Growth Factor (VEGF) were investigated in 30 cases (18 embryonal and 12 alveolar) available for this study. The IMVD-CD105 to IMVD-CD31 expression ratio was correlated with clinical and pathologic features of these patients. Results We found a specific expression of endoglin (CD105) in endothelial cells of all the rhabdomyosarcoma specimens analyzed. We observed a significant positive correlation between the IMVD individually measured by CD105 and CD31. The CD105/CD31 expression ratio was significantly higher in patients with lower survival and embryonal histology. Indeed, patients with a CD105/CD31 expression ratio

Bromelain is a mixture of proteolytic enzymes that is extracted primarily from pineapples. It is present in almost all the aerial parts of the plant—the peels, leaves, stems and fruit—although only the fruit and stems contain significant amounts. The market-demand for bromelain is quickly increasing, especially in the health sector as it can be used as a drug and/or nutraceutical. Although the complete molecular mechanism has not been fully identified, bromelain possesses several properties, including anti-inflammatory, anti-oedema, antithrombotic and fibrinolytic, mucolytic, anticancer and cicatrizing effects that have been evaluated in several clinical trials. However, one of the main limitations for the clinical use of this supplement is the varying composition of extracts, which leads to heterogeneity in results and, therefore, difficulty in making evidence-based prescriptions. In fact, different geographic locations, land and modes of cultivation, as well as extraction methods, can all give extracts with different activities, depending on the plant part used. Additionally, although novel extraction techniques have been developed to improve bromelain purification and extraction and give higher yields without loss in enzymatic activity, these methods are still expensive and challenging. This review will describe the state of the art in the main conventional and unconventional extraction and purification methods of bromelain and discuss the advantages and limitations of these strategies. Pharmacokinetic and pharmacodynamic profiles and the clinical applications that have arisen from randomized controlled clinical trials are also discussed. Finally, future perspectives for bromelain extracts will be presented.

Specific studies on stage IV rectal cancer are lacking. The aim of this study is to describe the current status of rectum-first approach (RFA), liver-first approach (LFA) and simultaneous approach (SA) in these patients. A systematic review was performed on PubMed, EMBASE and Cochrane including studies published from January 2005 to January 2021. Studies on colon cancer only, colon and rectal cancer without distinction, extrahepatic metastases at diagnosis, or case reports/letters were excluded. Main outcomes were 5-yr overall survival (OS) and treatment completion rates. 22 studies were included for a total of 1,653 patients. 77% of the studies were retrospective and mainly (59%) reported one treatment approach. The primary endpoint was declared in 27% of the studies. Irrespective of treatment approaches, the 5-yr OS rate was reported in 72% of the studies. The 5-yr OS rates ranged from 38.5% to 75% for LFA, from 28% and 80% for RFA and from 28.2% to 77.3% for SA. Treatment completion rates ranged from 50% to 100% for LFA, from 37% to 100% for RFA, and from 66% to 100% for SA. The wide heterogeneity of the results reflects that the therapeutic strategy in this setting is a case-by-case multidisciplinary decision and depends on several patient-specific features. [ABSTRACT FROM AUTHOR]

Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 10(15) cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.

Abstract Background The Accreditation Council for Graduate Medical Education (ACGME) implemented revisions to resident duty hour requirements (DHRs) in 2011 to improve patient safety and resident well-being. Perceptions of DHRs have been reported to vary by training stage and specialty among internal medicine and general surgery residents. The authors explored perceptions of DHRs among all residents at a large academic medical center. Methods The authors administered an anonymous cross-sectional survey about DHRs to residents enrolled in all ACGME-accredited core residency programs at their institution. Residents were categorized as medical and pediatric, surgery, or other. Results In total, 736 residents representing 24 core specialty residency programs were surveyed. The authors received responses from 495 residents (67%). A majority reported satisfaction (78%) with DHRs and believed DHRs positively affect their training (73%). Residents in surgical specialties and in advanced stages of training were significantly less likely to view DHRs favorably. Most respondents believed fatigue contributes to errors (89%) and DHRs reduce both fatigue (80%) and performance of clinical duties while fatigued (74%). A minority of respondents (37%) believed that DHRs decrease medical errors. This finding may reflect beliefs that handovers contribute more to errors than fatigue (41%). Negative perceived effects included diminished patient familiarity and continuity of care (62%) and diminished clinical educational experiences for residents (41%). Conclusions A majority of residents reported satisfaction with the 2011 DHRs, although satisfaction was significantly less among residents in surgical specialties and those in advanced stages of training.

Purpose: To determine the safety and efficacy of O-Arm™ intraoperative imaging in maxillofacial surgery of post-traumatic orbital fractures. In order to ensure correct placement of titanium plate, immediately after fixing, viewable, in the axial, sagittal and coronal images. Methods: The authors evaluated 5 consecutive adult patients with orbital fractures who required a reoperation involving displacement of titanium mesh between January and December 2015. The displacement or incorrect positioning of titanium mesh was detected at post-operative CT scan or clinical neurological findings. Intraoperative O-Arm™ imaging was used for our patients who underwent secondary maxillofacial orbital fracture surgery due to the failure of first surgical approach. Results: An eyelid incision was performed in order to obtain maximal exposure and minimizing cosmetic defects. Any previous fixation device was skeletonized and removed, any improperly reduced fracture was mobilized, reduced and refixated with 1.5 mm plates, screws and titanium mesh. The intra-operative O-Arm™ imaging technique was used at the end of the procedures. In 4 cases it confirmed the appropriateness of the newly obtained reconstruction, in 1 case a first scan showed a suboptimal result and the devices were correctly repositioned, guided by the O-Arm™ images. Conclusions: Intraoperative O-Arm™ assisted craniofacial reconstruction surgery improves the assessment of neurovascular structure decompression, skeletal fragment identification, fixation procedures and for the correct re-establishment of facial symmetry in orbital floor fractures.

Abstract Glucocorticoids (GCs) play important roles in developmental and physiological processes through the transcriptional activity of their cognate receptor (Gr). Using CRISPR/Cas9 technology, we established a zebrafish null Gr mutant line and compared its phenotypes with wild type and a zebrafish line with partially silenced gr (gr s357/s357 ). Homozygous gr −/− larvae are morphologically inconspicuous and, in contrast to GR −/− knockout mice, viable through adulthood, although with reduced fitness and early life survival. Mutants gr −/− are fertile, but their reproductive capabilities fall at around 10 months of age, when, together with cardiac and intestinal abnormalities already visible at earlier stages, increased fat deposits are also observed. Mutants show higher levels of whole-body cortisol associated with overstimulated basal levels of crh and pomca transcripts along the HPI axis, which is unresponsive to a mechanical stressor. Transcriptional activity linked to immune response is also hampered in the gr −/− line: after intestinal damage by dextran sodium sulphate exposure, there are neither inflammatory nor anti-inflammatory cytokine gene responses, substantiating the hypothesis of a dual-action of the GC-GR complex on the immune system. Hence, the zebrafish gr mutant line appears as a useful tool to investigate Gr functions in an integrated in vivo model.

To identify the main nursing diagnostic titles used in the care of critically ill patients hospitalized in an Intensive Care Unit, verifying the presence thereof in the diagnoses of NANDA International’s Taxonomy II. Methods: descriptive and documental study, in which 69 medical records of patients aged over 18 years were consulted. Results: 22 nursing diagnostic titles were found; the most frequent was risk for infection (99.0%), risk for skin integrity (75.0%) and risk for aspiration (61.0%). Most diagnoses were in the domains safety/ protection (43.0%) and activity/rest (26.5%). Conclusions: authors identified the main nursing diagnostic titles used in the care of critically ill patients admitted to the Intensive Care Unit and the presence thereof in the diagnoses of NANDA International’s Taxonomy II.

La trasposizione di lembi liberi microvascolari rappresenta oggi la procedura maggiormente diffusa nelle ricostruzioni del distretto testacollo. Tuttavia, non tutti i pazienti sono candidati ideali per ricostruzioni microvascolari, né tutti i difetti richiedono necessariamente lembi microvascolari per ottenere buoni risultati funzionali. Lo scopo di questo studio è quello di valutare se la ricostruzione di difetti del distretto testa-collo mediante lembi peduncolati sia inferiore alle ricostruzioni microvascolari in termini di complicanze, outcome funzionale e prognosi. In una coorte di pazienti consecutivi che sono stati sottoposti a resezione maggiore per carcinomi del distretto testa collo, abbiamo confrontato i dati delle ricostruzioni mediante lembi peduncolati con quelli delle ricostruzioni microvascolari. Tutti gli interventi sono stati eseguiti da un unico chirurgo dal 2006 al 2015. Sono stati inclusi un totale di 93 pazienti, la maggior parte dei quali affetti da carcinoma del cavo orale (n = 59), di cui 64 hanno subito ricostruzione tramite lembo peduncolato (69%). Nei due gruppi non si sono registrate differenze significative in termini di necrosi del lembo, complicanze ed outcome funzionale. Lanalisi multivariata ha mostrato che le comorbidità preoperatorie rappresentano lunico fattore significativo per il rischio di complicanze nella guarigione del lembo (p = 0,019). Nei due gruppi lanalisi di sopravvivenza e lanalisi di regressione proporzionale al rischio di recidiva di malattia o metastasi a distanza non hanno mostrato differenze significative. In questo studio retrospettivo di coorte, non randomizzato, i lembi peduncolati non sono risultati significativamente inferiori rispetto ai lembi liberi in termini complicanze, outcome e prognosi.

Background: Patient satisfaction surveys are vital to measuring a patient’s experience of care. How scores of patients managed by emergency medicine (EM) residents change as residents progress through training is not known. Objectives: To evaluate whether EM residents’ patient satisfaction scores improve as residency training progresses, similar to clinical skill improvement. Methods: A retrospective cross-sectional study evaluated the correlation of patient satisfaction scores with EM resident year of training from 2015 through 2017. We evaluated for a change in score over time for the 4 “physician questions” and the “overall” score. Results: We evaluated 1684 Press Ganey surveys linked to 40 EM resident physicians during the study period. The mean top box scores for the 4 physician questions (concern for comfort [ P = .72], courtesy [ P = .55], informative about treatment [ P = .46], and listening [ P = .91]) and overall assessment of emergency department care ( P = .51) were not significantly improved over the course of resident. Conclusion: We did not observe a difference in EM residents’ patient experience scores as their level of training progressed. Comprehensive patient experience training for residents might be needed.

Objetivo: avaliar o perfil clínico de pacientes acometidos por lesão por pressão em Unidade de Terapia Intensiva. Método: trata-se de um estudo descritivo transversal, realizado em hospital público terciário da cidade de Fortaleza. Foram inseridos no estudo 160 prontuários de pacientes que estiveram internados na unidade de terapia intensiva durante o ano de 2017 que desenvolveram lesão por pressão. Resultados: observou-se do total de prontuários analisados, 108 tiveram risco muito elevado de desenvolver lesão (67,5%), 49 manifestavam risco elevado (30,6%) e três deles, compreendiam a categoria de risco moderado para lesão por pressão (1,9%). Em relação a variável tempo de internação, 83 pacientes permaneceram internados por um período maior do que quatro semanas (51,9%). Sobre a quantidade de lesões, prevaleceu uma lesão nos casos avaliados (30,6%). Conclusão: conclui-se que o perfil clínico dos pacientes acometidos por lesão por pressão, prevaleceu pessoas maiores de 60 anos (54,4%), do sexo masculino (50,6%). 58 pessoas já entraram na UTI com LP (36,3%), e 55 desenvolveram LP na UTI, entre 1 a 2 semanas de internação na unidade (34,4%).

Euphausia superba, commonly known as krill, is a small marine crustacean from the Antarctic Ocean that plays an important role in the marine ecosystem, serving as feed for most fish. It is a known source of highly bioavailable omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In preclinical studies, krill oil showed metabolic, anti-inflammatory, neuroprotective and chemo preventive effects, while in clinical trials it showed significant metabolic, vascular and ergogenic actions. Solvent extraction is the most conventional method to obtain krill oil. However, different solvents must be used to extract all lipids from krill because of the diversity of the polarities of the lipid compounds in the biomass. This review aims to provide an overview of the chemical composition, bioavailability and bioaccessibility of krill oil, as well as the mechanisms of action, classic and non-conventional extraction techniques, health benefits and current applications of this marine crustacean.

Halloysite is an aluminosilicate clay with a predominantly hollow tubular structure (HNTs) able to act as a nanocontainer for the encapsulation of several chemicals. However, HNTs possess low affinity for metal ions in their pristine form and they need to be modified for improving their adsorption capabilities. Therefore, to overcome this issue herein we report a straightforward approach for the covalent modification of the external surface of halloysite nanotubes with hectorite clay. Compared to halloysite, hectorite possesses a lamellar structure with higher cation exchange capacity. The covalent linkage between the two clays was verified by several techniques (FTIR spectroscopy, 13C CP-MAS NMR, TGA, ζ−potential, DLS, and XRD measurements) and the morphology was imaged by TEM investigations. As proof of concept the adsorption ability of the obtained nanomaterial in comparison to pristine clays was proved using ciprofloxacin and silver ions chosen as models for their different chemical characteristics.

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a significant correlation of the Aβ 42/40 ratio with age at onset and Mini Mental State Examination (MMSE) scores. No significant correlation of Aβ 1–42 or Aβ 42/40 ratios to the rate of progression of the disease were found. Furthermore, when we stratified patients according to Aβ 1–42 concentration and the Aβ 42/40 ratio, we found that patients with a lower Aβ 42/40 ratio showed a shorter survival. Our results support the hypothesis that Aβ 1–42 could be involved in some pathogenic mechanism of ALS and we suggest the Aβ 42/40 ratio as a potential prognostic biomarker.

El establecimiento de relaciones diplomáticas entre Chile y Finlandia en 1918 fue producto del colapso del Imperio Ruso y el amanecer de la era Bolchevique. En el contexto de la Guerra Civil Rusa, Finlandia fue reconocida por las partes antagonistas de la I Guerra Mundial, y Chile se unió a las consideraciones de las potencias occidentales que veían la escisión de Finlandia como una oportunidad en lo económico y político. En este artículo se singulariza el papel de Agustín Edwards McClure, entonces embajador de Chile en Londres, en el momento en que también se empiezan a discutir las bases de la Liga de las Naciones y el nuevo elenco de naciones surgidas a partir del principio de autodeterminación de los pueblos, como era el caso finlandés.

Alessandro Colletti,1 Giuseppe Derosa,2 Arrigo FG Cicero1 1Department of Medical and Surgical Sciences, University of Bologna, Bologna, 2Department of Internal Medicine and Therapeutics, University of Pavia and Policlinico San Matteo Foundation, Pavia, Italy Abstract: Hypercholesterolemia is one of the main risk factors for atherosclerosis and cardiovascular diseases. The treatment is based on the modification of the diet and lifestyle and if necessary on a pharmacological therapy. The most widely used drugs are the inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (statins); nevertheless, many patients do not reach optimal levels of low-density lipoprotein-cholesterol (LDL-C) even with maximal dosage of statins (eventually associated to ezetimibe) or present side effects, which do not allow them to continue the treatment. Inhibitors of PCSK9 represent a new therapeutic approach for lowering LDL-C. Evolocumab and alirocumab are human monoclonal antibodies, which bind to extracellular PCSK9 and thus interfere with the degradation of low-density lipoprotein receptor. Evolocumab use is approved for the treatment of patients with heterozygous familial hypercholesterolemia (FH) and homozygous FH as an adjunct to diet and maximally tolerated statin therapy or for subjects with clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Phase III clinical trials have demonstrated the effectiveness of evolocumab (140 mg/every 2 weeks or 420 mg/month, via subcutaneous injection) in monotherapy and in combination with statins, in the treatment of patients intolerant to statins or with FH. In monotherapy, it reduces LDL-C by 55%, and its association with statins leads to a reduction of LDL-C by up to 63%–75%. Evolocumab has been demonstrated to be safe and well tolerated. Ongoing clinical trials are assessing the long-term effects of evolocumab on the incidence of cardiovascular risk, safety, and tolerability. This review resumes the available clinical evidence on the efficacy and safety of evolocumab, for which a relatively large amount of clinical data are currently available, and discusses the retargeting of cholesterol-lowering therapy in clinical practice. Keywords: PCSK9, hyperlipidemia, evolocumab, LDL-C, familial hypercholesterolemia

In this paper the electrolytic process application as a water purification treatment stage from the Ipê neighborhood lake (Ilha Solteira –São Paulo, Brazil–) was evaluated. The treatment efficiency for apparent and true color removal, in samples by addition of humic substances, to reach different colors levels was determined. It was monitored the 1 g/L NaCl and TiO2 addition individual effect. The removal efficiency for each trial in samples taken from the electrolytic reactor each 10 minutes during one hour, were calculated. For the water sample with initial apparent color of 25 Hu, it was reduced up to 15 Hu –maximum permitted value according the Brazilian drinking water guidelines– after 30 reaction minutes. For the apparent water color with 66 Hu, with sodium chloride addition, a reduction up to 13 Hu was measured after one hour reaction. In the trials with humic substances addition, the apparent color removal for water with 708 and 247 Hu, were 87.3 % and 84.2 %, respectively, after 60 minutes of reaction. The results showed the electrolytic process performance with use of salts as a drinking water treatment stage, both for the apparent color reduction below the maximum permitted values defined by the legislation, as for its removal up to certain levels, treatment stage that should be complemented by additional stages.

Summary: In utero hematopoietic stem/progenitor cell transplantation (IUHSCT) has only been fully successful in the treatment of congenital immunodeficiency diseases. Using sheep as a large animal model of IUHSCT, we demonstrate that administration of CD146+CXCL12+VEGFR2+ or CD146+CXCL12+VEGFR2− cells prior to, or in combination with, hematopoietic stem/progenitor cells (HSC), results in robust CXCL12 production within the fetal marrow environment, and significantly increases the levels of hematopoietic engraftment. While in the fetal recipient, donor-derived HSC were found to reside within the trabecular bone, the increased expression of VEGFR2 in the microvasculature of CD146+CXCL12+VEGFR2+ transplanted animals enhanced levels of donor-derived hematopoietic cells in circulation. These studies provide important insights into IUHSCT biology, and demonstrate the feasibility of enhancing HSC engraftment to levels that would likely be therapeutic in many candidate diseases for IUHSCT. : Almeida-Porada and colleagues show that after in utero transplantation, donor-derived HSC locate within the trabecular bone of the metaphysis, and that manipulation of the fetal vascular marrow niche, through transplantation of CD146+CXCL12+VEGFR2+ cells, boosts HSC engraftment to levels that would be therapeutic in many diseases.

Paola Di Carlo,1 Giuliana Guadagnino,1 Palmira Immordino,1 Giovanni Mazzola,2 Pietro Colletti,2 Ilenia Alongi,1 Lucia Adamoli,1 Francesco Vitale,1 Alessandra Casuccio1 1Department of Sciences for Health Promotion and Mother-Child Care “G D’Alessandro”, University of Palermo, 2Department of Medicinal Clinics and Emerging Diseases, “Paolo Giaccone” Polyclinic University Hospital, Palermo, Italy Aim: The authors examined a cohort of HIV-positive outpatients at the AIDS Center of Palermo University in Italy in order to identify factors related to the frequency of their visits to the outpatient facility for health care services.Methods: Two hundred and twenty-four HIV-infected subjects were enrolled in the study. Demographic and HIV disease characteristics were recorded and assessed with the number of days accessed to our outpatients unit in univariate and multivariate analyses. The potential relationship with immunological status was also analyzed stratifying the patients into groups according to their CD4+ T-cell counts (≥500 vs

Lo scopo di questo lavoro è quello di evidenziare come una metodica ricostruttiva inusuale, datata ed impopolare come il lembo di massetere possa invece rappresentare, per casi selezionati, una soluzione affidabile, semplice ed efficace nelle ricostruzioni del cavo orale. Riportiamo di seguito l’utilizzo del lembo di massetere in due pazienti che presentavano un secondo tumore del cavo orale e che in precedenza erano già stati sottoposti ad intervento chirurgico nel distretto testa collo; in entrambi i casi sono stati ottenuti eccellenti risultati funzionali e soddisfacenti risultati estetici. In letteratura, fino ad oggi, sono stati riportati solo 60 casi di ricostruzione del cavo orale e dell’orofaringe con il lembo di massetere. L’utilità clinica del lembo di massetere, anche nell’ambito di un approccio moderno alle ricostruzioni del distretto testa collo, viene discussa approfonditamente in questo articolo. Riteniamo che il lembo di massetere debba far parte del bagaglio culturale di ogni chirurgo del testa-collo ed essere considerato fra le alternative proponibili, in quanto ha dimostrato di essere una metodica elegante ed estremamente semplice in casi in cui sussistono delle perplessità sulle procedure microvascolari.

Potato peel (PP) is the major underutilised by-product in the potato-processing industry and a potential source of valuable bioactive molecules. Among them, glycoalkaloids and polyphenols are important precursors for steroid hormones and natural antioxidants, respectively. Moreover, the huge quantities of industrial potato-peel waste that are produced are a rich source of primary metabolites, which principally include starch as well as non-starch polysaccharides, proteins, lipids, lignin and cellulose. All carbohydrates are prone to undergo fermentation to produce ethanol, lactic and acetic acid. Finally, the main portion of PP is made up of alcohol-insoluble matter with a dietary fibre content of approximatively 40%. The present review summarises the recent advances and emerging technologies in potato-peel extraction and further valorisation processing in the food industry.

In recent years, increased awareness of the health benefits associated with consuming soy-based foods, knowledge of milk-related allergies and a move towards more sustainable food production have led to an increase in the number of available soy-based products. The biggest producers in the world, the USA, South America and China, are from the Pacific region. This enormous production is accompanied by the accumulation of related by-products, in particular, a substance that is known as okara. Okara is a paste that is rich in fibre (50%), protein (25%), fat (10%), vitamins and trace elements. Its proper use would lead to economic advantages and a reduction in the potential for polluting the environment. Its high fibre content and low production costs mean that it could also be used as a dietary supplement to prevent diabetes, obesity and hyperlipidaemia. Chemical or enzymatic treatment, fermentation, extrusion, high pressure and micronisation can all increase the soluble fibre content, and thus improve nutritional quality and processing properties. However, the product also degrades rapidly due to its high moisture content (70–80%), which makes it difficult to handle and expensive to dry by conventional means. The aim of this paper is therefore to thoroughly study the existing literature on this subject in order to develop a general protocol for okara exploitation and valorisation. A cost/benefit analysis could drive the design of eco-friendly, sustainable protocols for the preparation of high-value nutritional products.