The role of cattle in the transmission of cystic echinococcosis in a highly endemic area of the Peruvian Andes.

Cystic echinococcosis (CE) causes significant losses in Andean livestock production and affects Andean food security. However, more studies are needed to understand the epidemiology of the disease. In addition, the potential contribution of Andean cattle to the transmission of Echinococcus granulosus sensu lato needs to be known. This study aimed to determine the CE-prevalence and its association with risk factors, such as age and sex of the animals, the parasite load (number of cysts/organ) of condemned organs, and the viability and fertility of Echinococcus cysts from cattle in the Andes. The prevalence was examined in 348 cattle from an authorized slaughterhouse of Huancayo at 3300 m altitude. Cyst burden was determined by extracting all cysts from the total of the CE-infected organs. Cyst fertility and protoscolices viability were analysed from 90 randomly selected CE-infected organs. The CE prevalence was 35.6% (124/348; 95% CI: 30.6%-40.6%). There was no significant effect of age and sex on CE prevalence. CE was significantly more prevalent (p < 0.05) in lungs than livers, 34.8% (121/348; 95% CI: 29.8%-39.8%) vs 8.9% (31/348; 95% CI: 5.9%-11.9%). Most (75%) infected organs had one to five cysts. The mean cyst burden was significantly (p = 0.018) higher in the lungs than livers, 6.4 ± 4.9 vs 3.7 ± 2.9. Cyst fertility was 1.6% (10/608; 95% CI: 0.6%-2.6%). Despite the high CE prevalence, infected organs from Andean cattle play a minor role in CE transmission to dogs in the central Peruvian Andes.

Ecuación de referencia espirométrica en varones de 2 regiones del norte peruano ubicadas entre 0 a 100 metros sobre el nivel del mar: Estudio transversal

Objetivo: Determinar los valores de referencia de espirometría y formular una ecuación de predicción de valores espirométricos en población económicamente activa (PEA) de regiones con altitud 0-100 m.s.n.m. Métodos: Se seleccionaron a los participantes del estudio considerando los criterios de selección del estudio. Se recogió la información sobre las variables consideradas en el estudio: Capacidad Vital Forzada (CVF) y Volumen Espiratorio Forzado en el primer Segundo (VEF1), datos sociodemográficos y medidas antropométricas. Se dividió a la muestra en dos grupos para poder formular la ecuación de referencia y para evaluar su confiabilidad en un subgrupo de validación mediante las pruebas de correlación intraclase, T de Student para muestras pareadas y los gráficos de Bland-Altman. Resultados: Se seleccionaron 1052 participantes varones. Los rangos normales de CVF y VEF1 calculados fueron de CVF de 3.48 -5.47 y VEF1 de 2.83 - 4.41. Mediante una regresión lineal múltiple, se obtuvieron las siguientes fórmulas: CVF = 2.206 - 0.131 (Altitud Geográfica) - 0.014 (Edad) + 0.045 (Talla) y VEF1 = 1.589 - 0.08 (Altitud Geográfica) - 0.015 (Edad) + 0.033 (Talla). En los análisis de confiabilidad, se encontró una diferencia estadísticamente significativa en las medias entre los valores predichos por la ecuación y los valores reales, aunque en los gráficos de Bland-Altman no se evidenció un sesgo significativo y los coeficientes de correlación intraclase (CVF-ICC: 0.69; VEF1-ICC: 0.70) se encontraban dentro de un rango adecuado. Conclusiones: Las ecuaciones de CVF y VEF1 desarrolladas permiten predecir adecuadamente los valores espirométricos en PEA masculina de las regiones incluidas en el estudio.

Objective: Determine the spirometry reference values and formulate an equation to predict spirometric values in the economically active population (EAP) in regions with an altitude of 0-100 m.a.s.l. Materials and Methods: Study participants were selected considering the study selection criteria. Information was collected on the variables considered in the study: Forced Vital Capacity (FVC) and Forced Expiratory Volume in the first second (FEV1), sociodemographic data and anthropometric measurements. The sample was divided into 2 groups to be able to formulate the reference equation and to assess its reliability in a validation subgroup using intraclass correlation tests, Student's t-test for paired samples, and Bland-Altman plots. Results: 1052 male participants were selected. The normal ranges for FVC and FEV1 calculated were FVC 3.48 - 5.47 and FEV1 2.83 - 4.41. Using multiple linear regression, the following formulas were obtained: FVC = 2.206 - 0.131 (Geographic Altitude) - 0.014 (Age) + 0.045 (Height) and FEV1 = 1.589 - 0.08 (Geographic Altitude) - 0.015 (Age) + 0.033 (Height). In the reliability analyses, a statistically significant difference was found in the means between the values predicted by the equation and the real values, although the Bland-Altman plots did not show a significant bias and the intraclass correlation coefficients (FVC- ICC: 0.69; FEV1-ICC: 0.70) were within an adequate range. Conclusions: The developed FVC and FEV1 equations allow adequate prediction of spirometric values in male PEA of the regions included in the study.

Influence of Prebiotic Activity of Agave salmiana Fructans on Mucus Production and Morphology Changes in Colonic Epithelium Cell of Healthy Wistar Rats.

The beneficial health of evaluating prebiotic effect by the consumption of Agave salmiana fructans (A. salmiana fructans) was assessed in the epithelium of the cecum and proximal colon of Wistar rats fed at different doses for 35 days with regards to mucus production, morphological cell changes, and the serum concentration of tumor necrosis factor-α (TNF-α). Results showed a significant increase in mucus-secreting cells (P < 0.05) and a normal structure with preserved crypts, without morphological damage to colonic cells for a dose of 12.5% (w/w) with respect to the control and the other doses evaluated. The concentration of pro-inflammatory cytokine TNF-α was decreased significantly (P < 0.05) in the groups with doses of 10 and 12.5% (w/w) at 7 and 35 days, respectively. This effect was positively correlated with the reduction of inflammation in epithelial cells. This study provides direct evidence of the effects of the A. salmiana fructans on the colonic epithelium, demonstrating that a diet supplemented with 12.5% of fructans for 35 days exerts health benefits through the strengthening of the mucosa layer, which favors the adherence of the bacterial population and suppresses inflammation.

Comparison between 177Lu-iPSMA and 225Ac-iPSMA dosimetry at a cellular level in an animal bone metastasis model.

The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.

Physicochemical Properties, Antioxidant Capacity, Prebiotic Activity and Anticancer Potential in Human Cells of Jackfruit (Artocarpus heterophyllus) Seed Flour.

The general aim of this study was to evaluate physicochemical properties, prebiotic activity and anticancer potential of jackfruit (Artocarpus heterophyllus) seed flour. The drying processes of jackfruit seeds were performed at 50, 60 and 70 °C in order to choose the optimal temperature for obtaining the flour based on drying time, polyphenol content and antioxidant capacity. The experimental values of the moisture ratio during jackfruit seed drying at different temperatures were obtained using Page's equation to establish the drying time for the required moisture between 5 and 7% in the flour. The temperature of 60 °C was considered adequate for obtaining good flour and for performing its characterization. The chemical composition, total dietary fiber, functional properties and antioxidant capacity were then examined in the flour. The seed flour contains carbohydrates (73.87 g/100 g), dietary fiber (31 g/100 g), protein (14 g/100 g) and lipids (1 g/100 g). The lipid profile showed that the flour contained monounsaturated (4 g/100 g) and polyunsaturated (46 g/100 g) fatty acids. Sucrose, glucose, and fructose were found to be the predominant soluble sugars, and non-digestible oligosaccharides like 1-kestose were also found. The total polyphenol content was 2.42 mg of gallic acid/g of the sample; furthermore, the antioxidant capacity obtained by ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) was 901.45 µmol Trolox/100 g and 1607.87 µmol Trolox/100 g, respectively. The obtained flour exhibited good functional properties, such as water and oil absorption capacity, swelling power and emulsifier capacity. Additionally, this flour had a protective and preventive effect which is associated with the potential prebiotic activity in Lactobacillus casei and Bifidobacterium longum. These results demonstrate that jackfruit seed flour has good nutritional value and antioxidant and prebiotic activity, as well as potential protective effects and functional properties, making it an attractive food or ingredient in developing innovative functional products.

PREDATORY INTERACTION BETWEEN TWO ANURAN SPECIES WITH Thamnodynastes chaquensis (COLUBRIDAE) IN THE BRAZILIAN CERRADO / Interacción depredatoria entre dos especies de anura con Thamnodynastes chaquensis (Colubridae) en el Cerrado brasileño

ABSTRACT Although predatory events are uncommon to be recorded in nature, these data are important tools for understanding prey-predator interaction of the involved species. Snakes of genus Thamnodynastes are known for having an anuran diet, including some species of hylid frogs in their diet. Despite this, this pattern does not include T. chaquensis since there are no records on predation or trophic interaction with hylid frogs. Here, we report the first predatory interaction between T. chaquensis and two hylid frogs in Brazilian Cerrado. The first predation event with treefrog Boana caiapo occurred with success but, the second with B. albopunctata did not. Connecting trophic links within an ecosystem requires in-depth knowledge of its species and their intraspecific interactions. In this context, records of the predation and predation attempts such as these may help to connect unknown trophic links, which helps to understand aspects of the natural history of the species involved.

RESUMEN Aunque los eventos depredatorios son poco comunes de registrar en la naturaleza, estos datos son herramientas importantes para comprender la interacción presa-depredador de las especies involucradas. Las serpientes del género Thamnodynastes son conocidas por su dieta basada en anuros y, aunque algunas especies incluyen ranas hílidas en su dieta, esto no ocurre en la especie T. chaquensis porque no hay registros de depredación o interacción trófica con los hílidos. Aquí informamos sobre la primera interacción depredatoria entre T. chaquensis y dos ranas hílidas del Cerrado brasileño. El primer evento de depredación con la rana Boana caiapo fue exitoso, pero el segundo con B. albopunctata no. Conectar los enlaces tróficos dentro de un ecosistema requiere conocer íntimamente sus especies y sus interacciones intraespecíficas. En este contexto, los registros de depredación y de intentos de depredación como estos pueden ayudar a conectar enlaces tróficos no conocidos, lo cual ayuda a comprender los aspectos de la historia natural de las especies involucradas.

Imaging Features of Complications after Coronary Interventions and Surgical Procedures.

Coronary artery interventions and surgical procedures are used in the treatment of coronary artery disease and some congenital heart diseases. Cardiac and noncardiac complications can occur at variable times after these procedures, with the clinical presentation ranging from asymptomatic to devastating symptoms. Invasive coronary angiography is the reference standard modality used in the evaluation of coronary arteries, with intravascular US and optical coherence tomography providing high-resolution information regarding the vessel wall. CT is the mostly commonly used noninvasive imaging modality in the evaluation of coronary artery intervention complications and allows assessment of the stent, lumen of the stent, lumen of the coronary arteries, and extracoronary structures. MRI is limited to the evaluation of the proximal coronary arteries but allows comprehensive evaluation of the myocardium, including ischemia and infarction. The authors review the clinical symptoms and pathophysiologic and imaging features of various complications of coronary artery interventions and surgical procedures. Complications of percutaneous coronary interventions are discussed, including restenosis, thrombosis, dissection of coronary arteries or the aorta, coronary wall rupture or perforation, stent deployment failure, stent fracture, stent infection, stent migration or embolism, and reperfusion injury. Complications of several surgical procedures are reviewed, including coronary artery bypass grafting, coronary artery reimplantation procedure (for anomalous origin from opposite sinuses or the pulmonary artery or as part of surgical procedures such as arterial switching surgery and the Bentall and Cabrol procedures), coronary artery unroofing, and the Takeuchi procedure. Online supplemental material is available for this article. ©RSNA, 2021.

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

BACKGROUND: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. PATIENTS AND METHODS: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. RESULTS: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia. CONCLUSIONS: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

Stacking broiler litter to reduce natural hormones.

Estrone, 17ß-estradiol, and testosterone are naturally occurring hormones excreted in broiler litter. With some potential for environmental concern from the hormones, understanding management practices effect on hormone concentrations is beneficial for the poultry industry. As the amount of hormones potentially introduced into the environment is directly related to the concentration at the time of land application, the purpose of this study was to investigate hormone dynamics in stacked broiler litter during the storage period before removal from the farm and/or land application. Stack temperatures and hormones concentrations were monitored at 15, 45, 75 cm, and 105 cm (measured from the stack bottom) in 6 different on-farm stack houses over 4 or 8 wk. Significant differences in temperature were determined by height and by stack. Stack temperatures during the first 4 wk ranged from 41.5°C to 54.5°C, and all stacks reached maximum temperature by 7 D. Highest temperatures were observed at the 45-cm or 75-cm height. Average stack temperatures correlated with the ambient temperature. Hormone concentration did not vary with height within each house. In 5 of the 6 stack houses, the concentrations of 17ß-estradiol and/or testosterone significantly decreased after stacking for 4 or 8 wk (35 to 64%) with only one house showing a significant decrease in estrone concentration (72% in 4 wk). The percent change of estrone and 17ß-estradiol mineralization during the first 4 wk was negatively correlated with the 7-D temperature of the pile (r2 = 0.80), indicating that the high temperatures observed during stacking may inhibit estrogen mineralization. In this study, hormone degradation decreased with high temperatures. Therefore, stack management favoring at least a period of low temperatures may help promote mineralization of these hormones and reduce any potential for introduction into the surrounding environment.

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive, primary cutaneous neuroendocrine tumor that typically presents as an indurated nodule on sun-exposed areas of the head and neck in the white population. Major risk factors include immunosuppression, UV light exposure, and advanced age. Up to 80% of MCC are associated with Merkel cell polyomavirus. About 50% of patients present with localized disease, and surgical resection with or without adjuvant radiotherapy is generally indicated in this context. However, recurrence rates are high and overall prognosis rather poor, with mortality rates of 33%-46%. MCC is a chemosensitive disease, but responses in the advanced setting are seldom durable and not clearly associated with improved survival. Several recent trials with checkpoint inhibitors (pembrolizumab, avelumab, nivolumab) have shown very promising results with a favorable safety profile, in both chemonaïve and pretreated patients. In 2017, avelumab was approved by several regulatory agencies for the treatment of metastatic MCC, the first drug to be approved for this orphan disease. More recently, pembrolizumab has also been approved by the U.S. Food and Drug Administration in this setting. Immunotherapy has therefore become the new standard of care in advanced MCC. This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group. IMPLICATIONS FOR PRACTICE: Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyomavirus. MCC is a chemosensitive disease, but tumor responses in the advanced setting are short-lived with no long-term survivors. Recent clinical trials with immune checkpoint inhibitors (i.e., pembrolizumab, avelumab, nivolumab) have shown promising results, with avelumab becoming the first drug to receive regulatory approval for this orphan indication. Further follow-up is needed, however, to define more adequately the long-term benefits of these drugs, and continued research is warranted to optimize immunotherapeutic strategies in this setting.

External strain-enhanced cysteine enantiomeric separation ability on alloyed stepped surfaces.

Using density functional theory with an accurate treatment of van der Waals interactions, we investigate the enantioselective recognition and separation of chiral molecules on stepped metal surfaces. Our calculations demonstrate that the separation ability of metal substrates can be significantly enhanced by surface decoration and external strain. For example, applying 2% tensile strain to the Ag-alloyed Au(532) surface leads to a dramatic increase (by 89%) in cysteine enantioselectivity as compared to that of pristine Au(532). Analysis on the computed binding energies shows that the interaction energy is the predominant factor that affects the separation efficiency in strongly bound systems. Our study presents a new strategy to modify the enantioselectivity of stepped metal surfaces and paves the way for exploring high efficiency chiral separation technology in pharmaceutical industry.

Assessment of the radiation absorbed dose produced by 177Lu-iPSMA, 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a bone microenvironment model.

This research aimed to assess the radiation absorbed dose produced by 177Lu-iPSMA (177Lu-prostate specific membrane antigen inhibitor), 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a simplified model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that 225Ac-iPSMA releases a nine hundred-fold radiation dose greater than 177Lu-iPSMA and 14 times more than 223RaCl2 per unit of activity retained in bone. 225Ac-iPSMA could be the best option for treatment of bone metastases in prostate cancer.

Early life alcohol exposure primes hypothalamic microglia to later-life hypersensitivity to immune stress: possible epigenetic mechanism.

Growing evidence has shown that developmental alcohol exposure induces central nervous system inflammation and microglia activation, which may contribute to long-term health conditions, such as fetal alcohol spectrum disorders. These studies sought to investigate whether neonatal alcohol exposure during postnatal days (PND) 2-6 in rats (third trimester human equivalent) leads to long-term disruption of the neuroimmune response by microglia. Exposure to neonatal alcohol resulted in acute increases in activation and inflammatory gene expression in hypothalamic microglia including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Adults with neonatal alcohol pre-exposure (alcohol fed; AF) animals showed an exaggerated peripheral stress hormonal response to an immune challenge (lipopolysaccharides; LPS). In addition, there were significantly more microglia present in the hypothalamus of adult AF animals, and their hypothalamic microglia showed more cluster of differentiation molecule 11b (Cd11b) activation, TNF-α expression, and IL-6 expression in response to LPS. Interestingly, blocking microglia activation with minocycline treatment during PND 2-6 alcohol exposure ameliorated the hormonal and microglial hypersensitivity to LPS in AF adult animals. Investigation of possible epigenetic programming mechanisms by alcohol revealed neonatal alcohol decreased several repressive regulators of transcription in hypothalamic microglia, while concomitantly increasing histone H3 acetyl lysine 9 (H3K9ac) enrichment at TNF-α and IL-6 promoter regions. Importantly, adult hypothalamic microglia from AF animals showed enduring increases in H3K9ac enrichment of TNF-α and IL-6 promoters both at baseline and after LPS exposure, suggesting a possible epigenetic mechanism for the long-term immune disruption due to hypothalamic microglial priming.

Flue-gas desulfurization gypsum effects on urea-degrading bacteria and ammonia volatilization from broiler litter.

A major concern of the broiler industry is the volatilization of ammonia (NH3) from the mixture of bedding material and broiler excretion that covers the floor of broiler houses. Gypsum has been proposed as a litter amendment to reduce NH3 volatilization, but reports of NH3 abatement vary among studies and the mechanism responsible for decreasing NH3 volatilization is not well understood. The goal of this study was to evaluate the effect of adding 20 or 40% flue-gas desulfurization gypsum (FGDG) to broiler litter on pH, electrical conductivity (EC), water potential, urea-degrading bacteria abundance, NH3 and carbon dioxide (CO2) evolution, and nitrogen (N) mineralization in several 21-d experiments. The addition of FGDG to broiler litter increased EC by 24 to 33% (P < 0.0001), decreased urea-degrading bacteria by 48 to 57% (P = 0.0001) and increased N mineralization by 10 to 11% (P = 0.0001) as compared to litters not amended with FGDG. Furthermore, the addition of FGDG to broiler litter decreased NH3 volatilization by 18 to 28% (P < 0.0001), potentially resulting from the significantly lower litter pH values compared to un-amended litter (P < 0.0001). Findings of this study indicate that amending broiler litter with 20% FGDG can decrease NH3 volatilization and increase the fertlizer value of broiler litter.

Oral etoposide in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a very infrequent and aggressive skin tumor with high recurrence and metastasis rates. MCC treatment is currently not well defined. CASE PRESENTATION: We present the case of a 75-year-old woman who was diagnosed with MCC in 2010 and suffered a third relapse in 2012 which could not be treated surgically. RESULTS: The patient began oral etoposide treatment reaching complete response after eight cycles and receiving a total of 11 cycles. As side effects, the patient suffered from neutropenia, candidiasis and mucositis, but after reducing the dosage to 50% it was well tolerated. DISCUSSION: Chemotherapy treatment in this setting is poorly defined. In this case, monotherapy treatment with oral etoposide was decided due to the patient's age and comorbidities, achieving a very positive outcome.

Supramolecular polymerization of a prebiotic nucleoside provides insights into the creation of sequence-controlled polymers.

Self-assembly of a nucleoside on Au(111) was studied to ascertain whether polymerization on well-defined substrates constitutes a promising approach for making sequence-controlled polymers. Scanning tunneling microscopy and density functional theory were used to investigate the self-assembly on Au(111) of (RS)-N(9)-(2,3-dihydroxypropyl)adenine (DHPA), a plausibly prebiotic nucleoside analog of adenosine. It is found that DHPA molecules self-assemble into a hydrogen-bonded polymer that grows almost exclusively along the herringbone reconstruction pattern, has a two component sequence that is repeated over hundreds of nanometers, and is erasable with electron-induced excitation. Although the sequence is simple, more complicated ones are envisioned if two or more nucleoside types are combined. Because polymerization occurs on a substrate in a dry environment, the success of each combination can be gauged with high-resolution imaging and accurate modeling techniques. These characteristics make nucleoside self-assembly on a substrate an attractive approach for designing sequence-controlled polymers. Further, by choosing plausibly prebiotic nucleosides, insights may be provided into how nature created the first sequence-controlled polymers capable of storing information. Such insights, in turn, can inspire new ways of synthesizing sequence-controlled polymers.

Stacking Time and Aluminum Sulfate Effects on Polyether Ionophores in Broiler Litter.

The use of ionophores as antiparasitic drugs plays an important role in US poultry production, especially in the broiler () industry. However, administered ionophores can pass through the bird's digestive system and appear in broiler litter, which, when applied to agricultural fields, can present an environmental hazard. Stacking (storing or stockpiling) broiler litter for some time might decrease the litter ionophore concentrations before land application. Because ionophores undergo abiotic hydrolysis at low pH, decreasing litter pH with acidic aluminum sulfate (alum) might also decrease ionophore concentrations. We assessed the change in ionophore concentrations in broiler litter in response to the length of time broiler litter was stored (stacking time) and alum addition. We spiked broiler litter with monensin and salinomycin, placed alum-amended litter (∼pH 4-5) and unamended litter (∼pH 8-9) into 1.8-m bins, and repeatedly sampled each bin for 112 d. Our findings showed that stacking broiler litter alone did not have an impact on monensin concentration, but it did slowly reduce salinomycin concentration by 55%. Adding alum to broiler litter reduced monensin concentration by approximately 20% relative to unamended litter, but it did not change salinomycin concentration. These results call for continued search for alternative strategies that could potentially reduce the concentration of ionophores in broiler litter before their application to agricultural soils.

Laccase mediated transformation of 17ß-estradiol in soil.

It is known that 17ß-estradiol (E2) can be transformed by reactions mediated by some oxidoreductases such as laccase in water. Whether or how such reactions can happen in soil is however unknown although they may significantly impact the environmental fate of E2 that is introduced to soil by land application of animal wastes. We herein studied the reaction of E2 in a model soil mediated by laccase, and found that the reaction behaviors differ significantly from those in water partly because of the dramatic difference in laccase stability. We also examined E2 transformation in soil using (14)C-labeling in combination with soil organic matter extraction and size exclusion chromatography, which indicated that applied (14)C radioactivity was preferably bound to humic acids. The study provides useful information for understanding the environmental fate of E2 and for developing a novel soil remediation strategy via enzyme-enhanced humification reactions.

Neuronal bioenergetics and acute mitochondrial dysfunction: a clue to understanding the central nervous system side effects of efavirenz.

BACKGROUND: Neurological pathogenesis is associated with mitochondrial dysfunction and differences in neuronal/glial handling of oxygen and glucose. The main side effects attributed to efavirenz involve the CNS, but the underlying mechanisms are unclear. METHODS: Human cell lines and rat primary cultures of neurons and astrocytes were treated with clinically relevant efavirenz concentration. RESULTS: Efavirenz alters mitochondrial respiration, enhances reactive oxygen species generation, undermines mitochondrial membrane potential, and reduces adenosine triphosphate (ATP) levels in a concentration-dependent fashion in both neurons and glial cells. However, it activates adenosine monophosphate-activated protein kinase only in glial cells, upregulating glycolysis and increasing intracellular ATP levels, which do not occur in neurons. To reproduce the conditions that often exist in human immunodeficiency virus-related neuroinflammatory disorders, the effects of efavirenz were evaluated in the presence of exogenous nitric oxide, an inflammatory mediator and mitochondrial inhibitor. The combination potentiated the effects on mitochondrial parameters in both neurons and glial cells, but ATP generation and lactate production were enhanced only in glial cells. CONCLUSIONS: Efavirenz affects the bioenergetics of neurons through a mechanism involving acute mitochondrial inhibition, an action exacerbated in neuroinflammatory conditions. A similar scenario of glial cells survival and degeneration of neurons with signs of mitochondrial dysfunction and oxidative stress has been associated with neurocognitive disorders.

Inhibidores de la bomba de protones y la homeostasis del calcio / Proton pump inhibitors and calcium homeostasis

Antecedentes: la asociación entre los inhibidores de la bomba de protones (IBP) y el riesgo de osteoporosis y fracturas óseas es un tema que ha originado, recientemente, bastante interés en la literatura médica. Los IBP son los fármacos de primera elección en enfermedades que evolucionan con incremento de la secreción ácida y, debido al aumento progresivo de su prescripción, su potencial toxicidad se investiga periódicamente. Objetivos: en la presente revisión se analizan las bases fisiofarmacológicas y la limitada evidencia clínica de una potencial relación entre la administración continuada de IBP y la aparición de osteoporosis y fracturas óseas. Ambas patologías, relacionadas con la homeostasis del calcio, son de gran importancia en pacientes de edad avanzada por su mal pronóstico general y las consecuencias invalidantes que conllevan.

Background: the relationship between proton pump inhibitors (PPI) and the risk of osteoporosis and bone fractures is a topic of great interest in recent medical literature. PPI are first choice drugs for diseases evolving with an increase in acid secretion. Due to their growing prescription, their potential toxicity is periodically verified. Objectives: the present review analyzes the physiopharmacological bases and limited clinical evidence of a potential relationship between continued administration of PPIs and the appearance of osteoporosis and bone fractures. Both conditions are related to calcium homeostasis, and their relevance in elderly patients is high, due to their poor general prognosis and disabling effects.