Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies.

Although it is estimated that more than one million Americans have celiac disease (CD), it remains challenging to diagnose. CD, an autoimmune and inflammatory response following the ingestion of gluten-containing foods, has symptoms overlapping with other diseases and requires invasive diagnostics. The gold standard for CD diagnosis involves serologic blood tests followed by invasive confirmatory biopsies. Here, we propose a less invasive method using an electrochemical DNA (E-DNA) biosensor for CD-specific autoantibodies (AABs) circulating in blood. In our approach, CD-specific AABs bind a synthetic neoepitope, causing a conformational change in the biosensor, as well as a change in the environment of an attached redox reporter, producing a measurable current reduction. We assessed the biosensor's ability to detect CD-specific patient-derived AABs in physiological buffer as well as buffer supplemented with bovine serum. Our biosensor was able to detect AABs in a dose-dependent manner; increased signal change correlated with increased AAB concentration with an apparent dissociation constant of 0.09 ± 0.03 units/mL of AABs. Furthermore, we found our biosensor to be target-specific, with minimal off-target binding of multiple unrelated biomarkers. Future efforts aimed at increasing sensitivity in complex media may build upon the biosensor design presented here to further improve CD AAB detection and CD diagnostic tools.

[Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital]. / Estudio del impacto de la pandemia por SARS-CoV-2 en la práctica quirúrgica urgente y electiva en un hospital de tercer nivel.

Introduction: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. Methods: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. Results: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n = 10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). Conclusions: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.

Actions of p-synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver.

p-Synephrine is one of the main active components of the fruit of Citrus aurantium (bitter orange). Extracts of the bitter orange and other preparations containing p-synephrine have been used worldwide to promote weight loss and for sports performance. The purpose of the study was to measure the action of p-synephrine on hepatic enzyme activities linked to carbohydrate and energy metabolism and the levels of adenine mononucleotides. Enzymes and adenine mononucleotides were measured in the isolated perfused rat liver and in vivo after oral administration of the drug (50 and 300 mg/kg) by using standard techniques. p-Synephrine increased the activity of glycogen phosphorylase in vivo and in the perfused liver. It decreased, however, the activities of pyruvate kinase and pyruvate dehydrogenase also in vivo and in the perfused liver. p-Synephrine increased the hepatic pools of adenosine diphosphate and adenosine triphosphate. Stimulation of glycogen phosphorylase is consistent with the reported increased glycogenolysis in the perfused liver and increased glycemia in rats. The decrease in the pyruvate dehydrogenase activity indicates that p-synephrine is potentially capable of inhibiting the transformation of carbohydrates into lipids. The capability of increasing the adenosine triphosphate-adenosine diphosphate pool indicates a beneficial effect of p-synephrine on the cellular energetics.

A global network model of abiotic phosphorus cycling on Earth through time.

Phosphorus (P) is a crucial structural component of living systems and central to modern bioenergetics. P cycles through terrestrial geochemical reservoirs via complex physical and chemical processes. Terrestrial life has altered these fluxes between reservoirs as it evolved, which is why it is of interest to explore planetary P flux evolution in the absence of biology. This is especially true, since environmental P availability affects life's ability to alter other geochemical cycles, which could then be an example of niche construction. Understanding how P reservoir transport affects environmental P availability helps parameterize how the evolution of P reservoirs influenced the emergence of life on Earth, and potentially other planetary bodies. Geochemical P fluxes likely change as planets evolve, and element cycling models that take those changes into account can provide insights on how P fluxes evolve abiotically. There is considerable uncertainty in many aspects of modern and historical global P cycling, including Earth's initial P endowment and distribution after core formation and how terrestrial P interactions between reservoirs and fluxes and their rates have evolved over time. We present here a dynamical box model for Earth's abiological P reservoir and flux evolution. This model suggests that in the absence of biology, long term planetary geochemical cycling on planets similar to Earth with respect to geodynamism tends to bring P to surface reservoirs, and biology, including human civilization, tends to move P to subductable marine reservoirs.

Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital. / Estudio del impacto de la pandemia por SARS-CoV-2 en la práctica quirúrgica urgente y electiva en un hospital de tercer nivel.

INTRODUCTION: SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. METHODS: We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. RESULTS: During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). CONCLUSIONS: The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.

Habitability Models for Astrobiology.

Habitability has been generally defined as the capability of an environment to support life. Ecologists have been using Habitat Suitability Models (HSMs) for more than four decades to study the habitability of Earth from local to global scales. Astrobiologists have been proposing different habitability models for some time, with little integration and consistency among them, being different in function to those used by ecologists. Habitability models are not only used to determine whether environments are habitable, but they also are used to characterize what key factors are responsible for the gradual transition from low to high habitability states. Here we review and compare some of the different models used by ecologists and astrobiologists and suggest how they could be integrated into new habitability standards. Such standards will help improve the comparison and characterization of potentially habitable environments, prioritize target selections, and study correlations between habitability and biosignatures. Habitability models are the foundation of planetary habitability science, and the synergy between ecologists and astrobiologists is necessary to expand our understanding of the habitability of Earth, the Solar System, and extrasolar planets.

Isolation of UV-B resistant bacteria from two high altitude Andean lakes (4,400 m) with saline and non saline conditions.

Laguna (L.) Negra and L. Verde are high altitude Andean lakes located at the 4,400 m altitude in the Andean desert (Puna) in the Argentine northwest. Both lakes are exposed to extreme weather conditions but differ in salinity contents (salinity 6.7% for L. Negra and 0.27% for L. Verde). The aim of this work was to isolate ultraviolet B fraction (UV-B) resistant bacteria under UV-stress in order to determine, a possible connection, between resistance to UV-B and tolerance to salinity. DNA damage was determined by measuring CPDs accumulation. Connection among pigmentation production and UV resistance was also studied. Water samples were exposed to artificial UV-B radiation for 24 h. Water aliquots were plated along the exposition on different media, with different salinity and carbon source content (Lake medium (LM) done with the lake water plus agar and LB). CFU were counted and DNA damage accumulation was determined. Isolated bacteria were identified by 16S rDNA sequence. Their salinity tolerance, were measured at 1, 5 and 10% NaCl and their pigment production in both media was determined. In general it was found that UV resistance and pigment production were the optimum in Lake Medium done with lake water which maintained similar salinity. The most resistant bacteria in L. Negra were different strains of Exiguobacterium sp. and, in L. Verde, Staphylococcus sp. and Stenotrophomonas maltophilia. These bacteria showed the production and increase of UV-Vis absorbing compounds under UV stress and in LM. Bacterial communities from both lakes were well adapted to high UV-B exposure under the experimental conditions, and in many cases UV-B even stimulated growth. The idea that resistance to UV-B could be related to adaptation to high salinity is still an open question that has to be answered with future experiments.

Gold Nanoparticle-Functionalized Reverse Thermal Gel for Tissue Engineering Applications.

Utilizing polymers in cardiac tissue engineering holds promise for restoring function to the heart following myocardial infarction, which is associated with grave morbidity and mortality. To properly mimic native cardiac tissue, materials must not only support cardiac cell growth but also have inherent conductive properties. Here, we present an injectable reverse thermal gel (RTG)-based cardiac cell scaffold system that is both biocompatible and conductive. Following the synthesis of a highly functionalizable, biomimetic RTG backbone, gold nanoparticles (AuNPs) were chemically conjugated to the backbone to enhance the system's conductivity. The resulting RTG-AuNP hydrogel supported targeted survival of neonatal rat ventricular myocytes (NRVMs) for up to 21 days when cocultured with cardiac fibroblasts, leading to an increase in connexin 43 (Cx43) relative to control cultures (NRVMs cultured on traditional gelatin-coated dishes and RTG hydrogel without AuNPs). This biomimetic and conductive RTG-AuNP hydrogel holds promise for future cardiac tissue engineering applications.

Immune pathogenesis of Mixed Connective Tissue Disease: a short analytical review.

Mixed Connective Tissue Disease (MCTD) was first described 35 years ago by Gordon C. Sharp and his colleagues. In the ensuing decades, a clearer understanding of the clinical and serologic features of MCTD has emerged. Classification criteria now exist to define MCTD for study purposes, the long-term outcome of the disease has been established, and novel genetic associations within the major histocompatibility complex on chromosome 6 and select regions on chromosome 3 have been identified. Studies on immune pathogenesis have made substantial progress in advancing our understanding of MCTD. In MCTD, there is a complex interaction of the innate and adaptive immune system that culminates in autoimmune disease. Antigenic structural modification occurring during apoptosis or other modifications of self antigens leads to an autoantigen driven immune process with innate immune activation, immunoglobulin G autoantibody production directed against select components of the spliceosome, B lymphocyte activation, and CD4 and CD8 T lymphocyte participation.

Comparative effects of L-DOPA and velvet bean seed extract on soybean lignification.

Velvet bean (Mucuna pruriens) is an efficient cover forage that controls weeds, pathogens and nematodes, and the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA) is its main allelochemical. The effects of 3 g L-1 of an aqueous extract of velvet bean seeds, along with 0.5 mM L-DOPA for comparison, were evaluated in roots, stems and leaves of soybean (Glycine max). The activities of phenylalanine ammonia lyase (PAL) and cinnamyl alcohol dehydrogenase (CAD) were determined, along with the lignin content and its monomeric composition. The results revealed similar effects caused by L-DOPA and the aqueous extract. Both treatments reduced PAL and CAD activities, lignin, and lignin monomer contents in roots; PAL and CAD activities in stems, and CAD activity in leaves. These findings provide further evidence that the effects of velvet bean cover forage on root lignification were due to the L-DOPA, its major allelochemical.

Draft Genome Sequence of the Polyextremophilic Halorubrum sp. Strain AJ67, Isolated from Hyperarsenic Lakes in the Argentinian Puna.

Halorubrum sp. strain AJ67, an extreme halophilic UV-resistant archaeon, was isolated from Laguna Antofalla in the Argentinian Puna. The draft genome sequence suggests the presence of potent enzyme candidates that are essential for survival under multiple environmental extreme conditions, such as high UV radiation, elevated salinity, and the presence of critical arsenic concentrations.

Aplicación actual de la clasificación Inmunohistoquímica de cáncer de mama / Current Applicaton of Immunohistochemistry in Breast Cancer

Introducción: El cáncer de mama es la primera causa de mortalidad en el mundo y en Guatemala ocupa el segundo lugar en frecuencia. Desde 1991 su clasifcación ha evolucionado a fn de mejorar el pronóstco y su tratamiento basado en la descripción del tpo y grado histológico. El objetvo de este estudio es conocer la aplicación actual de la inmunohistoquímica en cancer de mama. Metodología: Estudio observacional descriptvo retrospectvo, sobre cáncer de mama clasifcado por inmunohistoquímica en 281 pacientes en el Insttuto Guatemalteco de Seguridad Social (IGSS) de enero 2012 a enero del 2017. Resultados: El subtpo Luminal A se presentó en el 31% de los pacientes y su tratamiento fue principalmente hormonal; seguido por el Triple Negatvo en el 26% tratado mayoritariamente con quimioterapia. El HER2 Positvo en el 21%, el subtpo B-like 13% y en menor frecuencia el Luminal B en el 9% de los casos. El subtpo triple negatvo presento mayor recurrencia y mortalidad con mayor elevación del P53 (40%, OR 2.4) y Ki67 (37%, OR 1.4). La edad en la mayoría de pacientes incluidas fueron superiores a los 40 años y los estadios II y III se presentaron con mayor frecuencia. Conclusiones: El estudio de la inmunohistoquímica realizado en los tejidos obtenidos permitó mostrar que el subtpo luminal A fue el más frecuente, recibiendo en la mayoría de los casos tratamiento hormonal. El más agresivo en recurrencia, metástasis, mortalidad y con valor elevado del Gen p53 y Ki67, fue el Triple Negatvo, tratado con quimioterapia.

Background: Breast cancer is the leading cause of death in the world, and in Guatemala it is the second most common cause of death. Since 1991, its classifcaton has evolved in order to improve prognosis and treatment based on the descripton of type and histological grade. The purpose of this study is to learn the current applicaton of immunohistochemistry of breast cancer. Methods: This retrospectve descriptve observatonal study of breast cancer classifed by immunohistochemistry was performed on 281 patents at the Guatemalan Social Security Insttute (IGSS) between January 2012 and January 2017. Results: The subtype Luminal A was present in 31% of the patents and treatment was mainly hormonal; followed by Triple Negatve in 26% of patents treated mainly with chemotherapy. HER2 positve in 21% of patents, subtype B-like in 13% and lower frequency Luminal B in 9% of the patents. The triple negatve subtype presented higher recurrence and mortality with P53 elevaton (40%, OR 2.4) and Ki67 (37%, OR 1.4). Average age in the study was 40 years old and stages II and III were more frequent. Conclusions: The study of immunohistochemistry performed on tssue obtained, demonstrated that Luminal A subtype is the most frequent, in which the majority of patents received hormonal treatment. The most aggressive in recurrence, metastasis, mortality and with high values of gene p53 and Ki67, was the Triple Negatve, which were treated with chemotherapy.

Circulating 20S proteasome levels in patients with mixed connective tissue disease and systemic lupus erythematosus.

The associations of circulating 20S proteasomes (c20S) with clinical and serologic disease indices in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are unknown. We present the initial report that c20S levels are elevated in MCTD and correlate with clinically relevant changes in disease activity in SLE and MCTD.

Clinical and immunologic manifestations of mixed connective tissue disease in a Miami population compared to a Midwestern US Caucasian population.

OBJECTIVE: A cross-sectional study of mixed connective tissue disease (MCTD) was performed to determine if there were identifiable differences in the clinical expression of MCTD associated with race or ethnicity. METHODS: Miami, Florida, and Midwestern US (Missouri) Caucasian MCTD cohorts were studied. Clinical and laboratory features of the 2 MCTD cohorts were compared. A concurrently collected cohort of Sm-positive patients with systemic lupus erythematosus (SLE) was studied as a control. Disease activity and severity and functional status were measured. CD4+CD25(high)-expressing T-regulatory cells were enumerated and serum soluble L selectin was measured as biomarkers of disease activity. RESULTS: The Miami and Missouri Caucasian MCTD groups, while differing from the SLE group, were largely similar; however, gastroesophageal reflux, sclerodactyly, and malar rash were significantly more frequent in the Missouri MCTD group and alopecia was more frequent in the Miami MCTD group. Significant clinical and laboratory differences were found between the Miami MCTD and Miami SLE groups despite similar disease duration, activity, severity and functional status. Raynaud's phenomenon (RP), hand swelling, synovitis, myositis, and sclerodactyly were all significantly more common in RNP-positive MCTD versus Sm-positive SLE subjects. CONCLUSION Ethnic differences were observed in the frequency of end-organ involvement in the Miami MCTD versus the Missouri Caucasian MCTD groups. Clinical and laboratory features of all MCTD groups were clearly different from the SLE group, despite similar disease activity, disease severity, and functional status. Disease activity measures appeared to behave similarly as valid measures of disease activity in SLE and MCTD.

Neuropsychiatric systemic lupus erythematosus presenting as amyotrophic lateral sclerosis.

A 61-year-old woman with a history of photosensitive dermatitis and recurrent mouth ulcers presented with progressive weakness typical of amyotrophic lateral sclerosis (ALS), and subsequently underwent extensive neurologic and rheumatologic testing. We investigated whether ALS-like motor neuron disease associated with a positive antinuclear antibody (ANA) is really ALS or rather neuropsychiatric systemic lupus erythematosus (NPSLE). On neurologic evaluation, she had prominent bulbar involvement with dysarthria and dysphagia associated with profound lingual fasciculations and a denervating pattern on electromyogram. MRI showed no evidence of cerebral ischemia. Laboratory studies revealed a positive ANA (1:2560 titer), positive antiphospholipid antibodies (GPL and MPL), circulating lupus anticoagulant, and depressed C3 and C4. Repeat MRI studies at 4 and 11 mo revealed an evolving infarct in the paramedian pons consistent with the presence of NPSLE. Therapy was initiated with corticosteroids and intravenous cyclophosphamide, and the neurologic condition did not improve, but also did not progress inexorably as would be expected with ALS. NPSLE, presumably through the mechanism of ischemic vasculopathy, may present as motor neuron disease clinically indistinguishable from ALS.

The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus.

OBJECTIVE: To determine the incidence and prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) and glomerulonephritis in ethnically diverse pediatric onset SLE inpatient and outpatient populations. METHODS: Seventy-five pediatric onset patients with SLE including Native American, Asian, Black, Spanish-American, and Caucasian subjects were evaluated prospectively and cross sectionally. During the 6 year study, 55 patients became inpatients. Subjects underwent medical interview, physical examination, laboratory review, neuropsychiatric inventory, and chart review. Classification of NPSLE was accomplished with the 1999 ACR NPSLE case definitions. RESULTS: Prospectively, NPSLE occurred in 95% of pediatric SLE patients and was more common than glomerulonephritis (55%; p < or = 0.0001). NPSLE prevalence (%) and incidence (event/person/yr) were as follows: headache 72%, 95; mood disorder 57%, 0.41; cognitive disorder 55%, 0.49; seizure disorder 51%, 0.94; acute confusional state 35%, 0.6; anxiety disorder 21%, 0.28; peripheral nervous system disorder 15%, 0.16; cerebrovascular disease 12%, 0.32; psychosis 12%, 0.16; chorea 7%, 0.01; demyelinating syndrome 4%, 0.01; and myelopathy 1%, 0.001. Cross sectionally, active NPSLE was present in 93% of inpatients and 69% of outpatients. When only serious forms of NPSLE were considered (stroke, seizures, major cognitive disorder, chorea, psychosis, major depression, acute confusional state), serious or life-threatening NPSLE occurred in 76% of all SLE subjects prospectively, and in 85% and 40% of inpatients and outpatients cross sectionally, which in each instance was more common than glomerulonephritis (p < or = 0.001). CONCLUSION: NPSLE is one of the most common serious complications of pediatric SLE, and is particularly increased in pediatric inpatients.