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The evidence regarding benefits of high-flow nasal cannula (HFNC) in patients with COVID-19 is controversial. The aim of this study was to evaluate the impact of HFNC in comparison with standard oxygen therapy on the frequency of endotracheal intubation at 28 d in subjects with acute hypoxemic respiratory failure (AHRF) secondary to SARS-CoV-2 infection.A retrospective, age- and sex-matched-paired, cohort study was conducted in subjects with moderate-to-severe AHRF. Intervention group was treated with HFNC, and control group was treated with standard oxygen therapy. Baseline characteristics and clinical evolution were analyzed. Mantel-Haenszel test was used for categorical variables. Paired samples Wilcoxon test was used for quantitative variables. Multivariate analysis was performed using conditional multiple logistic regression.Eighty-four subjects were included. The median time from admission to progression of oxygen therapy to FIn this study, HFNC therapy in subjects with AHRF secondary to COVID-19 was not an independent predictor of endotracheal intubation, compared with standard oxygen therapy, after adjusting for confounders.

Robert S Epstein,1 Upal K Basu Roy,2 Matti Aapro,3 Tehseen Salimi,4 Donald Moran,4 JoAnn Krenitsky,1 Megan L Leone-Perkins,5 Cynthia Girman,6 Courtney Schlusser,7 Jeffrey Crawford8 1Epstein Health, LLC., Woodcliff Lake, NJ, USA; 2LUNGevity Foundation, Bethesda, MD, USA; 3Clinique De Genolier, Genolier, Switzerland; 4G1 Therapeutics Ltd., Research Triangle Park, NC, USA; 5HealthiVibe, a Division of Corrona, LLC., Arlington, VA, USA; 6Chapel Hill Consulting, LLC., Chapel Hill, NC, USA; 7UNC Gillings School of Global Public Health, Chapel Hill, NC, USA; 8Duke University Medical Center, Durham, NC, USACorrespondence: Robert S EpsteinEpstein Health, LLC., Woodcliff Lake, NJ, 07677, USATel +1 201-285-5800Email repstein@epsteinhealth.comPurpose: To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the “patient voice” describing how CIM impacts their daily lives.Participants and Methods: Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥ 1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: “In your own words, please describe how side effects from myelosuppression have impacted your life.”Results: Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1– 10 scale of “bothersomeness”). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24– 43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family.Conclusion: Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.Keywords: cancer, chemotherapy, myelosuppression, real world, quality of life, patient burden

Background and Overview Molar-incisor hypomineralization (MIH) is a qualitative developmental defect of enamel, which has been a daily concern in clinical practice owing to its difficult treatment. Case Description An 11-year-old girl was admitted to the pediatric dental clinic with a symptom of severe hypersensitivity in the permanent molars owing to MIH. The treatment consisted of a simplified occlusal replica adapted technique with conventional glass ionomer cement in the MIH-affected molars, which involved laboratory and clinical stages. The patient was reexamined every 3 months, and after 18 months there was no additional tooth structure loss, restoration failure, or pain. This technique may be considered a feasible alternative to restore hypomineralized teeth owing to its reduced procedure time and good performance in the follow-up period of 18 months. Conclusions and Practical Implications The technique successfully restored the function and shape of the affected teeth, decreasing the sensitivity by means of covering the demarcated MIH opacities.

Introduction Chemotherapy-induced myelosuppression (CIM) is one of the most common dose-limiting complications of cancer treatment, and is associated with a range of debilitating symptoms that can significantly impact patients’ quality of life. The purpose of this study was to understand patients’ perspectives on how the side effects of CIM are managed in routine clinical practice. Methods An online survey was conducted of participants with breast, lung, or colorectal cancer who had received chemotherapy treatment within the past 12 months, and had experienced at least one episode of myelosuppression in the past year. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Results Of 301 participants who completed the online survey, 153 (51%) had breast cancer, 100 (33%) had lung cancer, and 48 (16%) had colorectal cancer. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Most participants (79%) reported having received treatment for CIM, and 64% of participants recalled chemotherapy dose modifications as a result of CIM. Although most participants believed their oncologist was aware of the side effects of CIM, and treated them quickly, 30% of participants felt their oncologists did not understand how uncomfortable they were due to the side effects of CIM. Overall, 88% of participants considered CIM to have a moderate or major impact on their lives. Conclusion The data highlight that despite the various methods used to address CIM, and the patient-focused approach of oncologists, the real-world impact of CIM on patients is substantial. Improving communication between patients and health care providers may help improve patients’ understanding of CIM, and foster shared decision-making in terms of treatment. Additional insights from patients should be obtained to further elucidate the totality of life burden associated with CIM., Plain Language Summary This study looked at people with cancer who received chemotherapy and developed a condition where their bone marrow activity was reduced, called myelosuppression. This meant they had fewer red blood cells that carry oxygen around the body, white blood cells that help fight infections, and platelets that help the blood to clot. The researchers wanted to understand how chemotherapy-induced myelosuppression affects peoples’ lives and their cancer treatment, and people’s experiences of treatment for myelosuppression. Overall, 301 people in the USA with breast, lung, or large bowel (colorectal) cancer completed an online survey. They had all received chemotherapy in the last year, and had myelosuppression at least once during their treatment. The survey showed that around 8 in 10 people (79%) had to be treated for myelosuppression, and around 7 in 10 people (73%) felt they received treatment for myelosuppression quickly. Chemotherapy was delayed, reduced, or stopped because of myelosuppression in around 6 in 10 people (64%). Around 3 in 10 people (30%) felt their oncologist did not understand the discomfort that myelosuppression caused them, and around 9 in 10 people (88%) felt that myelosuppression made their quality of life worse. The researchers concluded that because myelosuppression impacts peoples’ lives and their ability to keep receiving chemotherapy to treat their cancer, effective prevention and treatment for this condition are important. Better communication between people and their health care teams could help them to understand how people experience myelosuppression and make plans for treatment together.

Transient neurological deficits can occur in the setting of subdural hemorrhages with subsequent unremarkable electrodiagnostic and radiological evaluation. This scenario is rare and can be difficult for physicians to interpret. These transient neurological deficits are thought to result from relative ischemia, secondary to a lesser-known concept known as cortical spreading depolarization. These transient neurological deficits are thought to result from relative ischemia, secondary to a lesser-known concept known as cortical spreading depolarization, which may present clinically as nonepileptic, stereotypical, and intermittent symptoms (NESIS). In these instances, patients are often misdiagnosed as epileptics and committed to long-term antiseizure drugs. We present a 51-year-old patient developing acute global aphasia following the evacuation of a subdural hematoma, with no significant findings on laboratory, microbiological, electrodiagnostic, or radiological evaluation. The patient experienced spontaneous improvement and returned to baseline in the subsequent weeks. Increased awareness of NESIS as a cortical spreading depolarization phenomenon can improve patient care and prevent both unnecessary, extended medical evaluations and therapeutic trials.

This article establishes a dialogue between disability studies and ecocriticism to analyze Sara Mesa’s novel Cara de pan (2018), which narrates the relationship between a thirteen-year-old girl bullied at school and a fifty-four-year-old man with an atypical appearance who fixates on limited topics. The analysis examines the hegemony of normativity and dominant social narratives about disability, gender, and sexuality. Grounded in the idea that people with disabilities actively intervene in their environment, the essay argues that the characters’ environmental empathy supports the need for a diversity of experiences and perspectives, positively resituating disability and autism.

It was hypothesized that activity exercise at professional levels could lead to an increase in metabolic levels and a decrease in performance parameters. These trends are explained by physical activity as a cellular stressor.We used an algorithm, Laboratory Index which evaluates salivary cortisol, CK and d-ROMs, collected previously from elite Italian soccer players, compared to InStat Index. The last one estimates analytically the athlete's performance in soccer pitch, applying the Heath Maps.A good agreement between the two Index was obtained, especially for two players, who showed an ideal combined trend.We would investigate the clinical and activity profile of soccer players with the aim of providing information for the development of training strategies. Also, the performances, during training and match time, are an objective evaluation of the athlete's physical preparation. As a consequence, the combination of two Index could be used for a new approach to the sports world.

ObjectiveTo investigate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi), deep brain stimulation (DBS) on individual action tremor/postural tremor (AT) and rest tremor (RT) in Parkinson’s disease (PD). Randomized DBS studies have reported marked benefit in tremor with both GPi and STN and DBS, however, there is a paucity of information available on AT vs RT when separated by the surgical target.MethodsWe retrospectively reviewed the 1-year clinical outcome of PD patients treated with STN and GPi DBS at the University of Florida. We specifically selected patients with moderate to severe AT. Eighty-eight patients (57 STN and 31 GPi) were evaluated at 6 and 12 months for changes in AT and RT in the OFF-medication/ON stimulation state. A comparison of “response” was performed and defined as greater than or equal to a 2-point decrease in tremor score.ResultsSTN and GPi DBS both improved AT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). The STN DBS group experienced a greater improvement in AT at 6 months compared to the GPi group (p = 0.005) but not at the 12 months follow-up (p = 0.301). Both STN and GPi DBS also improved RT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). There was no difference in RT scores between the two groups at 6 months (p = 0.23) or 12 months (p = 0.74). The STN group had a larger proportion of patients who achieved a “response” in AT at 6 months (p < 0.01), however, this finding was not present at 12 months (p = 0.23). A sub-analysis revealed that in RT, the STN group had a larger percentage of “responders” when followed through 12 months (p < 0.01).ConclusionBoth STN and GPi DBS reduced PD associated AT and RT at 12 months follow-up. There was no advantage of either brain target in the management of RT or AT. One nuance of the study was that STN DBS was more effective in suppressing AT in the early postoperative period, however, this effect diminished over time. Clinicians should be aware that it may take longer to achieve a similar tremor outcome when utilizing the GPi target.

Merkel cell carcinoma (MCC) of the skin is a rare but aggressive cutaneous neuroendocrine-derived malignancy that predominantly affects elderly white males. The presence of distant nodal metastases significantly impacts survival. Typical metastatic sites of MCC are liver, bone, brain and skin. Gastrointestinal metastases are uncommon and small bowel is the most common site followed by stomach. We report a case of symptomatic MCC jejunal metastasis.

Introduction The management of acute postoperative pain remains a significant challenge for physicians. Poorly controlled postoperative pain is associated with poorer overall outcomes. Methods Between April and May 2017, physicians from an online database who regularly prescribe intravenous (IV) medications for acute postoperative pain completed a 47-question survey on topics such as patient demographics, IV analgesia preferences, factors that influence prescribing decisions, and the challenges and unmet needs for the treatment of acute postoperative pain. Results Of 501 surveyed physicians, 55% practiced in community hospitals, 60% had been in practice for > 10 years, and 60% were surgeons. The three categories of IV pain medications most likely to be prescribed to patients with moderate-to-severe pain immediately after surgery were morphine, hydromorphone, or fentanyl (95.8% of respondents); COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (73.7%); and acetaminophen (60.5%). Past clinical experience (81.6%), surgery type (78.2%), and onset of analgesia (67.1%) were practice-related factors that most determined their medication choice. Key patient-related risk factors, such as avoidance of medication-related adverse events (AEs), each influenced prescription decisions in > 75.0% of physicians. Nausea and vomiting were among the most common challenges associated with postoperative pain management (76.2 and 60.3%, respectively), and avoidance of analgesic medication-related AEs was among the three most influential patient-related factors that determined prescribing decision (75%). Physicians reported the top unmet need for acute pain management in patients experiencing moderate-to-severe postoperative pain was more medications with fewer side effects (i.e., nausea, vomiting, and respiratory depression; 80.7%). Conclusions Opioids remain an integral component of multimodal acute analgesic therapy for acute postoperative pain in hospitalized patients. The use of all IV analgesic medications is limited by concerns over AEs, particularly with opioids and in high-risk patients. There remains a key unmet need for effective analgesic medications that are associated with a lower risk of AEs. Funding Trevena, Inc. Electronic supplementary material The online version of this article (10.1007/s40122-018-0106-9) contains supplementary material, which is available to authorized users.

The Niles-Wolford Mound (33Pi3) was a conical Adena burial mound located along the Scioto River in Jackson Township, Pickaway County, Ohio. Excavations conducted in 1955 by the Ohio History Connection resulted in the discovery of a subfloor tomb with three burials. A tubular pipe found in association with one of the burials contained charred organic residue. Macrobotonical analysis of the material identified root or bark within the sample. Liquid chromatography-mass spectrometry (LC-MS) analyses detected the presence of various compounds, including an alkaloid. Radiocarbon dating places the mound to circa 2120 ± 30 BP. This research furthers our understanding of the timing, geographical extent, and ceremonial contexts of prehistoric plant tobacco use by the Adena culture and demonstrates the importance of museum collections for addressing such questions.

This paper addresses Iberian ecocritical approaches and cultural responses to ecological degradation through an examination of Rosa Montero’s futuristic novels Lágrimas en la lluvia (2011) and its sequel El peso del corazón (2015). In these works, contaminated natural resources, cloning, and teleportation for interplanetary travel contribute to new social hierarchies, existential crises, and heightened xenophobia in Europe, now part of the United States of the Earth. This study places particular emphasis on the novels’ criticisms of a North-South divide, in which the use and distribution of natural resources reflects the inequitable burden of environmental contamination and economic exploitation on the world’s southern zones. Montero’s novels posit that interspecies alliances across different geographical regions respond to these inequities. Rob Nixon’s ecocritical work on slow environmental violence, Spanish economist Amaia Pérez Orozco’s writings on feminist economics and collaborative care, and the theory and activism of various ecofeminists underscore Montero’s critique of a global economic system that exploits the environment and the marginalized. These theorists and activists argue that social justice, sustainability, and a non-materialist conception of well-being must replace the dominant androcentric approaches to economics and to social relations, which foster growing inequity and environmental contamination. Resumen Este trabajo hace hincapié en acercamientos ecocríticos y respuestas culturales a la degradación ecológica a través de las novelas futuristas de Rosa Montero Lágrimas en la lluvia (2011) y la secuela El peso del corazón (2015). En estas obras, los recursos naturales contaminados, la clonación, y el teletransporte interplanetario contribuyen a nuevas jerarquías sociales, crisis existenciales y aumento en la xenofobia en Europa, que ya es parte de los Estados Unidos de la Tierra. Este estudio pone énfasis en la crítica que llevan a cabo estas novelas de una división norte-sur en que el uso y la distribución de los recursos naturales reflejan la carga desigual de la contaminación medioambiental y la explotación económica de las zonas periféricas del mundo. Las novelas de Montero proponen que las alianzas entre especies a través de diversas regiones geográficas responden a dichas desigualdades. Entre otras, la obra ecocrítica de Rob Nixon sobre la violencia lenta medioambiental, los estudios de la economista española Amaia Pérez Orozco sobre económica feminista y cuidado colaborativo, y la teoría y el activismo ecofeministas subrayan la crítica de Montero a un sistema económico global que explota el medio ambiente y a los marginados. Estos teóricos y activistas proponen que la justicia social, la sostenibilidad de la vida y una concepción no materialista del bienestar deben reemplazar los acercamientos androcéntricos dominantes en la economía y las relaciones sociales que animan una creciente desigualdad social y contaminación medioambiental.

Appendiceal mucocele represents specimen finding in 0.2-0.3% out of appendectomies. The rupture or perforation in peritoneal cavity might cause pseudomixoma peritonei (PMP), with multiple mucinous deposits in the abdominal cavity. We report a case of PMP caused by a perforated appendiceal cistoadeonoma.

This review is a perspective on the history of Chagas disease, and it adopts a novel approach from literary studies, historical documents and the science and epidemiology of the nature of the disease. From this analysis, comes the review's working definition of the Contact Zone (CZ): “the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships, which usually involve coercive conditions, radical inequality and intolerable conflict.” In the Patient-Physician CZ, we verified the triple transition phenomena: the American trypanosomiasis shifted from a rural, acute, and vectorial transmitted disease to an urban, chronic and non-vectorial disease. In the Academic CZ, we describe the original disagreements which denied the existence of the disease and the current controversies about pathogenic mechanisms and etiological treatment. From the News from Latin America, and in the Original CZ, we will review the evolution of different forms of transmission. As in any good story, research across broad disciplines is necessary to reveal historical perspectives, scientific approaches, and the epidemiology of the disease, which has a prequel of 9000 years and an open ending: thus, we explore across the Global CZ, with its multiple and unexpected actors. Fil: Chao, Chen. Fundación Favaloro; Argentina Fil: Leone, José L.. No especifíca; Fil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina

Resumen El embalse Cabra Corral es el principal sitio de recreación y pesca deportiva del noroeste argentino, existe un gran interés en la preservación de sus condiciones ambientales. El Cabra Corral recibe desde el río Arenales materia orgánica proveniente de efluentes domiciliarios e industriales, como de actividades ganaderas y agrícolas que se desarrollan en el valle de Lerma; también recibe una importante contribución de minerales desde el río Guachipas. En este cuerpo de agua se ha encontrado altos niveles de mercurio y cadmio. Evaluamos las condiciones sanitarias de las poblaciones de Odonthestes bonariensis del embalse Cabra Corral, que presenta un alto impacto antrópico en relación con las poblaciones de otro embalse, el Campo Alegre con menor impacto antrópico. Analizamos marcadores histopatológicos en órganos blanco a fin de establecer si existen diferencias entre los dos cuerpos de agua. Realizamos muestreos bimensuales, se extrajeron muestras de hígado, riñón y branquias, las que se procesaron con técnicas histológicas de rutina; se analizaron muestras de agua para determinar su calidad. En el embalse Cabra Corral encontramos un gran número de histopatologías, el hígado es el órgano más afectado, seguido por el riñón y en menor medida las branquias. En el embalse Campo Alegre, las histopatologías también se hallaron pero en menor proporción. En el Cabra Corral se destacan las parasitosis hepáticas y renales causadas por coccidios asociados a procesos inflamatorios. La identificación y evaluación de los marcadores histopatológicos confirmó que existen marcadas diferencias en el estado de salud de las poblaciones de O. bonariensis entre los dos embalses estudiados. Abstract The Cabra Corral reservoir is the main recreational and sport fishing area of northwest Argentina, with a great interest in the preservation of its environmental conditions. From the Arenales river, the Cabra Corral receives organic matter from domestic and industrial effluents, as well as livestock and agricultural activities of the Lerma Valley. To this is added an important contribution of minerals from the Guachipas river. High levels of mercury and cadmium have been found in this body of water. We assess the health conditions of Odonthestes bonariensis of the Cabra Corral reservoir, which are subject to a very high anthropic impact in relation to the populations of the species in another reservoir of the province, such as the Campo Alegre reservoir. We analyzed histopathological markers in white organs in order to establish if there are differences between the two bodies of water. We performed bi-monthly samplings, extracting samples of liver, kidney and gills, which were processed with routine histological techniques. In addition, water samples were analyzed for quality. In the Cabra Corral reservoir, we found a large number of histopathologies, where the liver was the most affected organ, followed by the kidney and, to a lesser extent, the gills. In the Campo Alegre reservoir, we found a lower proportion of histopathologies. Liver and kidney parasites caused by coccidia associated with inflammatory processes are reported in fish population in Cabra Corral area. The identification and evaluation of histopathological markers confirmed that there are marked differences in the health status of O. bonariensis between the two reservoirs.

This paper addresses Iberian ecocritical approaches and cultural responses to ecological degradation through an examination of Rosa Montero’s futuristic novels "Lágrimas en la lluvia" (2011) and its sequel "El peso del corazón" (2015). In these works, contaminated natural resources, cloning, and teleportation for interplanetary travel contribute to new social hierarchies, existential crises, and heightened xenophobia in Europe, now part of the United States of the Earth. This study places particular emphasis on the novels’ criticisms of a North-South divide, in which the use and distribution of natural resources reflects the inequitable burden of environmental contamination and economic exploitation on the world’s southern zones. Montero’s novels posit that interspecies alliances across different geographical regions respond to these inequities. In this analysis, Rob Nixon’s ecocritical work on slow environmental violence, Spanish economist Amaia Pérez Orozco’s writings on feminist economics and collaborative care, and the theory and activism of various ecofeminists underscore Montero’s critique of a global economic system that exploits the environment and the marginalized. These theorists and activists argue that social justice, sustainability, and a non-materialist conception of well-being must replace the dominant androcentric approaches to economics and to social relations, which foster growing inequity and environmental contamination., Este trabajo hace hincapié en acercamientos ecocríticos y respuestas culturales a la degradación ecológica a través de las novelas futuristas de Rosa Montero "Lágrimas en la lluvia" (2011) y la secuela "El peso del corazón" (2015). En estas obras, los recursos naturales contaminados, la clonación, y el teletransporte interplanetario contribuyen a nuevas jerarquías sociales, crisis existenciales y un aumento en la xenofobia en Europa, que ya es parte de los Estados Unidos de la Tierra. Este estudio pone énfasis en la crítica que llevan a cabo estas novelas de una división norte-sur en que el uso y la distribución de los recursos naturales reflejan la carga desigual de la contaminación medioambiental y la explotación económica de las zonas periféricas del mundo. Las novelas de Montero proponen que las alianzas entre especies a través de diversas regiones geográficas responden a dichas desigualdades. En este análisis, la obra ecocrítica de Rob Nixon sobre la violencia medioambiental, los estudios de la economista española Amaia Pérez Orozco sobre económica feminista y cuidado colaborativo, y la teoría y el activismo ecofeministas subrayan la crítica de Montero a un sistema económico global que explota el medio ambiente y a los marginados. Estos teóricos y activistas proponen que la justicia social, la sostenibilidad de la vida y una concepción no materialista del bienestar deben reemplazar los acercamientos androcéntricos dominantes en la economía y las relaciones sociales que animan una creciente desigualdad social y contaminación medioambiental.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Objectives: The rapid spread of infections due to antibiotic-resistant, Gram-negative bacteria in Europe and surrounding regions requires a heightened level of awareness among physicians within their practice settings. Methods: We surveyed 800 physicians who treat these infections across France, Germany, Spain, Italy, and Russia to assess their awareness of best management approaches. Results: We found that more than two-thirds do not consider themselves highly aware of best management practices. The respondents are facing these resistant infections as evidenced by the antibiotics they report using and their stated interest in newer agents. Respondents indicated that precious time is lost waiting for culture results, but also said they will need more information about accuracy, use, and costs for adopting rapid molecular testing. Conclusions: The survey further identified the need for treatment guidelines and clinical decision support tools that can be applied at the bedside.

Effigy mounds occur across the midcontinent of North America but their cultural purposes and construction chronologies are rarely known and often controversial. Determining the age and construction history of monuments is important to relate religious symbolism, scientific knowledge, and cultural continuity to groups within a region. Based mainly on circumstantial evidence, researchers have long held that Serpent Mound in Ohio, USA, was constructed 2000–3000 years ago during the Early Woodland (Adena) or Middle Woodland (Hopewell) periods. Excavations in 1991 recovered charcoal buried at shallow depths (35–45 cm) in fill units of the mound and the 14C ages from two of these units indicated that Serpent Mound was built ∼900 years ago, during the Late Prehistoric (Fort Ancient) period, much later than originally thought. Our recent multidisciplinary work provides a more complex, robust construction history of Serpent Mound. We used geophysics to map the mound, and solid-earth cores to provide accurate stratigraphy and organic samples for 14C age estimates from the base of the mound. Bayesian statistical analyses of the seven 14C ages from Serpent Mound suggest that it was first constructed ∼2300 years ago during the Early Woodland (Adena) period but was renovated 1400 years later during the Late Prehistoric (Fort Ancient) period, probably to repair eroded portions of the mound. Modification of the mound is also indicated by a possible abandoned coil that is located near the head of the Serpent and visible only in the magnetometer survey.

In 2004-2005, salvage excavations at the Madisonville Village and Cemetery Site, a Late Fort Ancient settlement in southwestern Ohio, provided an opportunity to gather new information concerning post-A.D. 1550 occupation at the site. This article documents the use histories of excavated features and their resultant archaeobotanical remains. Results indicate that Madisonville features have incredibly complex formation histories which reflect continual reuse of a geographically restricted landform. Archaeobotanical analysis indicates a high reliance on maize by site inhabitants, although such reliance was not constant but instead increased threefold over time. Maize agriculture was supplemented by a diversity of additional cultigens (e.g., beans, erect knotweed, little barley, sunflower, and squash) and wild foods, especially nut resources, which remained an important dietary component throughout Madisonville's long occupation.

The association between proton pump inhibitor (PPI) therapy and hypomagnesaemia has been recognized since 2006. We report the case of a 51-year-old woman who developed severe symptomatic hypomagnesaemia after a long-term PPI therapy given for recurrent peptic ulcer disease. Hypomagnesaemia could only partially be resolved during substitution therapy, but was corrected after withdrawal of the PPI. Recurrence of hypomagnesaemia occurred after retreatment with PPIs, supporting the causal relationship. An underlying gastric acid hypersecretion (Zollinger-Ellison syndrome) was highly suspected and eventually controlled by a combination of a histamine 2-receptor antagonist and octreotide, without the need for further PPI therapy after 2 years of follow-up.

The Adena Mound (33RO1) is the type site of the Adena culture, yet there have been no radiocarbon dates to place it reliably within a temporal framework. Fortunately, the artifact collection, curated by the Ohio Historical Society, includes objects that are highly suitable for radiocarbon dating, including fragments of textiles and tree bark associated with the central burial. We selected a textile fragment and two bark fragments for radiocarbon dating. The textile exhibits alternate pair twine with very fine yarns probably composed of cellulose bast fibers. The bark is from a black locust (Robinia pseudoacacia) tree. The results of the radiocarbon dating indicate that the Adena Mound was constructed between the end of the second century B.C. and the beginning of the first century A.D., placing it near the midpoint in the sequence of radiocarbon-dated Adena culture sites. This study demonstrates the value of museum collections for gleaning new data from curated materials.

The objective of the present study was to evaluate the clinicopathological features and the survival time estimates in patients treated for borderline ovarian tumors (BOTs). A retrospective review of all patients treated for BOTs at the University of Bari (Bari, Italy) between 1991 and 2011 was performed. Data were obtained from hospital records and gynecological oncology charts. A total of 55 patients were identified. The median age was 40 years (range, 13–79 years). The majority of the patients (85.5%) exhibited International Federation of Obstetrics and Gynecology (FIGO) stage I disease and the remainder exhibited FIGO stage II/III (7.3% in each stage). Serous histology was found in 60.0% of the cases and an elevation of the cancer antigen-125 serum level occurred in 23.6% of the cases. All patients underwent surgery and 3.7% received chemotherapy. In total, 10.9% exhibited recurrence and the median survival rate was 39 months. The median survival time and the five-year survival rate were 42 months (range, 16–84 months) and 97%, respectively. Therefore, BOTs have an excellent prognosis. Conservative surgery should be considered for patients of reproductive age who desire preservation of fertility. A long-term follow-up is highly recommended for these tumors.

Literary representations of global migration to Spain have augmented in concert with the increase in immigration at the turn of the twenty-first century. While these texts tend to express an empathetic stance toward the hardships that immigrants face, they often fall short in capturing the complexity of the nation’s changing ethnic composition and critically engaging with the issue of a Spanish author narrating the stories of subjects who have immigrated to the Iberian nation. This essay proposes that in Cosmofobia (2007), Lucía Etxebarria purposefully addresses the potentially colonizing position of authoring a fictional text about immigrant experiences in Spain, with narrative strategies that highlight her role in creating the work that we read and that attend to an ethical elaboration of a transnational feminist project. The author’s representation of gender and place in the context of an intricate social web in global Madrid suggests that concerns common to women of different ethnicities may reshape conceptions of community and create new spaces for interethnic collaboration.

De novo design has proven a powerful methodology for understanding protein folding and function, and for mimicking or even bettering the properties of natural proteins. Extensive progress has been made in the design of helical bundles, simple structural motifs that can be nowadays designed with a high degree of precision. Among helical bundles, the four-helix bundle is widespread in nature, and is involved in numerous and fundamental processes. Representative examples are the carboxylate bridged diiron proteins, which perform a variety of different functions, ranging from reversible dioxygen binding to catalysis of dioxygen-dependent reactions, including epoxidation, desaturation, monohydroxylation, and radical formation. The "Due Ferri" (two-irons; DF) family of proteins is the result of a de novo design approach, aimed to reproduce in minimal four-helix bundle models the properties of the more complex natural diiron proteins, and to address how the amino acid sequence modulates their functions. The results so far obtained point out that asymmetric metal environments are essential to reprogram functions, and to achieve the specificity and selectivity of the natural enzymes. Here, we describe a design method that allows constructing asymmetric four-helix bundles through the covalent heterodimerization of two different α-helical harpins. In particular, starting from the homodimeric DF3 structure, we developed a protocol for covalently linking the two α2 monomers by using the Cu(I) catalyzed azide-alkyne cycloaddition. The protocol was then generalized, in order to include the construction of several linkers, in different protein positions. Our method is fast, low cost, and in principle can be applied to any couple of peptides/proteins we desire to link.

Traditionally, the positive correlation between red hair and melanoma has been attributed to both the poor antioxidant and photoprotective properties of pheomelanins compared to the dark eumelanins, and the capacity of pheomelanin to act as photosensitizer inducing generation of reactive oxygen species upon UV irradiation. Recently, the occurrence of UV-independent pathways of carcinogenesis was provided by a series of experiments showing that induction of an activating mutation of BRAF into red mice resulted in a high incidence of invasive melanomas in the absence of UV stimulation . In addition, the skin of pheomelanic mice contained higher levels of oxidative DNA and lipid damage with respect to albino-Mc1re/e mice (Mitra et al, Nature 2012, 491, 449-453). These data clearly showed that the pheomelanin pathway could mediate oxidative stress and melanomagenesis ; however the mechanisms have not so far addressed at molecular level. To get an insight into these processes we investigated the reactivity of pheomelanin pigment isolated from human red hair (RHP) and synthetic pheomelanins from cysteinyldopa (CD-Mel) toward critical cellular antioxidants such as GSH and NAD(P)H. Data showed a remarkable increase in the oxidation rate of both compounds in the presence of RHP compared to the controls, whereas much less marked variations were noticed with the eumelanin extracted from black hair. HPLC analysis consistently indicated a rise in GSH disulfide (GSSG) levels with GSH decrease, confirming a redox reaction. Formation of NAD(P)+ was similarly observed in the reaction mixture of NAD(P)H with RHP. In the absence of oxygen, GSH and NAD(P)H depletion was not observed while the presence of enzymes as superoxide dismutase and catalase did not modify the effect of pheomelanin suggesting a ROS independent mechanism. Similar effects were obtained with CD-Mel confirming that the prooxidant effects are due to the pheomelanic component. The mechanism of GSH oxidation by RHP was investigated by EPR spectroscopy. Besides inducing antioxidant depletion, RHP, like CD-Mel, proved also capable of promoting autoxidation of melanin precursors, such as 5-S-cysteinyldopa and dopa, under conditions of exclusion of light, with formation of pheomelanin or eumelanin pigments. This effect is oxidative in character, since it depends on oxygen, revealing a remarkable prooxidant capacity of the pigment serving as a biocatalyst for non-enzymatic melanogenesis (Panzella et al., PCMR 2014, 27,244-252; Greco et al. Chem Comm. 2011,47, 10308-10310). A mechanism has been proposed to account for the observed effects in which GSH, NAD(P)H and melanin precursors oxidation is not mediated by ROS, but is the result of a direct redox exchange with oxidized 1,4-benzothiazine units within the pigment scaffold. Re-oxidation of reduced pheomelanin by oxygen with formation of ROS would ensure shuttling of pheomelanin between the redox states. Overall these results provide a unifying chemical framework into which to explain the mechanisms underlying the relationships between pheomelanin pigmentation and oxidative stress.

Objectives: The aim of this study was to evaluate the role of neoadjuvant chemotherapy (NACT) in advanced ovarian carcinoma patients unable to undergo a complete resection during primary debulking surgery. Methods: From February 2005 to October 2015, all consecutive cases of advanced-stage epithelial ovarian carcinoma at the University of Bari were retrospectively recorded. Of them, patients treated with NACT were collected. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors of survival. Results: Seventy-eight women with advanced-stage epithelial ovarian carcinoma were treated with NACT. On univariate analysis, age (p = 0.003), CA-125 serum level (0.001), response to NACT (p < 0.0001), stage of disease (p = 0.011) and optimal debulking surgery (p < 0.0001) were found to be important prognostic factors related to survival. However, on multivariate analysis, age, response to NACT, CA-125 serum level and optimal debulking surgery remained as independent poor prognostic factors for survival. The median overall and disease-free survival were 31 and 12 months, respectively. Conclusions: NACT does not compromise survival in patients with stage IIIC and IV ovarian cancer compared to patients treated with primary surgery. Prospective randomized trials comparing NACT to conventional treatment are needed to determine the quality of life and cost/benefit outcomes for women presenting advanced epithelial ovarian cancer.

Eight measurement campaigns for the characterization of atmospheric aerosol properties were conducted from 2001 until 2008 at five sites located in the Western Mediterranean basin. Radiometric measurements were used to obtain Aerosol Optical Depth, Ångström parameters, and aerosol size distributions, allowing differentiation of background conditions from anthropogenic, marine, or Saharan dust aerosol advection. The analysis was focused on the study of optical and physical properties variation of atmospheric aerosols under Saharan outbreaks. Dust-affected data were analysed all together, independently from the measurements site, thus allowing the highlighting of similarities and differences among them. The scatter-plot Ångström exponent versus AOD at 780 nm shows a correlation among all dust data, while an overlapping region with no-dust data reveals the simultaneous presence of mineral, anthropogenic, and marine particles. Daily averaged volume size distributions can be unimodal or bimodal functions and one three-modal distribution, with a coarse mode generally prevailing. Finally, considering the ratio of small/large particles 𝑛𝑠/𝑛𝑙 and plotting the corresponding histogram for all dust data, a sharp frequency distribution is obtained with 89% of data in the range 5–65, while 89% of no-dust data extend from 5 to 135, in spite of different sources, pathways, and arrival sites.