Toxicogenomics of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants.

Optical fiber pH sensor based on a multimode interference device with polymer overlay.

An optical fiber pH sensor based on a multimode interference structure is presented. The sensitive element is a piece of no-core fiber (NCF) coated with a mixture of polyallylamine hydrochloride and polyacrylic acid by a modified layer-by-layer (LbL) self-assembly method. It is experimentally shown that by reducing the diameter of the NCF by chemical etching, the sensitivity is increased from -0.31n m/p H to -2n m/p H. The sensor exhibits a high linear response of 0.997 over a pH range from 5 to 11.3 with a rapid response time lower than 1 s.

Development of video tutorials to help parents manage children with acute illnesses using a modified Delphi method.

AIM: Children often fall sick, which causes concern among parents. Online health information can be confusing and difficult to understand. We aimed to produce simple, informative video tutorials on the symptoms ill children present. METHODS: We used a modified Delphi method to produce video tutorials on the symptoms of fever, vomiting and diarrhoea, abdominal pain, breathing difficulties, sore throat, red eyes, earache and rash. We identified the most common symptoms in acutely ill children. During the first consensus round, experts rated statements on out-of-hospital management from existing health information. Video tutorials were produced from statements rated to be included. The second consensus round involved video showings and editing. Two videos were evaluated in focus groups by parents. RESULTS: During the first round, experts rated a median of 79 (40-154) statements for each symptom. Panels consisted of a median of seven (6-11) experts, primarily. Panels reached a consensus on inclusion, neutrality or exclusion in 83% of statements. The second round led to adjustments to the videos and final approval by experts. Most parents evaluated the videos as 'informative, easy to understand and calming'. CONCLUSION: We produced video tutorials on the common symptoms ill children present using a modified Delphi method. Feedback from parents in focus groups was positive.

Pegbovigrastim use in periparturient embryo-recipient cows: Effects on health and reproduction.

The objective of this randomized clinical study was to evaluate the effects of periparturient administration of pegbovigrastim (recombinant bovine granulocyte colony stimulating factor; PEG) on postpartum health and reproductive outcomes in dairy cows carrying transferred embryos. A total of 60 multiparous Jersey cows (second parity n = 21, >second parity n = 39) that were in vitro-fertilized embryo recipients were enrolled. Animals were selected from a commercial herd and assigned to 1 of 2 treatments: (1) PEG (n = 31), which received a subcutaneous injection of 15 mg of PEG 7 d before expected calving and a second dose within 1 h of parturition; or (2) CON, untreated control (n = 29). Parturition was induced pharmacologically in all cows at 280 d of pregnancy with 500 µg of cloprostenol and 25 mg of dexamethasone intramuscularly. Cow health was monitored daily during the periparturient period and included assessment for retained fetal membranes within 24 h after calving and metritis until 20 d in milk. Descriptive statistics were calculated, to determine the incidence of postpartum diseases, causes of culling, and early-lactation reproductive outcomes, including number of inseminations, days to first heat, days to first service, and interval from calving to conception. The Wilcoxon rank sum test was used to assess treatment effects on early-lactation reproductive performance outcomes. The overall incidence of metritis in this cohort of cows was 17.14%. Animals treated with PEG tended to have more cases of metritis (25%) compared with CON (8.8%). Mastitis incidence in PEG was 19.35% compared with CON at 27.59%. These data suggest that in this dairy, with embryo-recipient cows induced to calve at 280 d of pregnancy, the administration of 2 doses of PEG tended to increase postpartum metritis but had no effect on mastitis incidence, culling rate, or early-lactation reproductive outcomes.

Inter-annual variability patterns of reef cryptobiota in the central Red Sea across a shelf gradient.

The combination of molecular tools, standard surveying techniques, and long-term monitoring programs are relevant to understanding environmental and ecological changes in coral reef communities. Here we studied temporal variability in cryptobenthic coral reef communities across the continental shelf in the central Red Sea spanning 6 years (three sampling periods: 2013-2019) and including the 2015 mass bleaching event. We used a combination of molecular tools (barcoding and metabarcoding) to assess communities on Autonomous Reef Monitoring Structures (ARMS) as a standardized sampling approach. Community composition associated with ARMS for both methodologies (barcoding and metabarcoding) was statistically different across reefs (shelf position) and time periods. The partition of beta diversity showed a higher turnover and lower nestedness between pre-bleaching and post-bleaching samples than between the two post-bleaching periods, revealing a community shift from the bleaching event. However, a slight return to the pre-bleaching community composition was observed in 2019 suggesting a recovery trajectory. Given the predictions of decreasing time between bleaching events, it is concerning that cryptobenthic communities may not fully recover and communities with new characteristics will emerge. We observed a high turnover among reefs for all time periods, implying a homogenization of the cryptobiome did not occur across the cross shelf following the 2015 bleaching event. It is possible that dispersal limitations and the distinct environmental and benthic structures present across the shelf maintained the heterogeneity in communities among reefs. This study has to the best of our knowledge presented for the first time a temporal aspect into the analysis of ARMS cryptobenthic coral reef communities and encompasses a bleaching event. We show that these structures can detect cryptic changes associated with reef degradation and provides support for these being used as long-term monitoring tools.

The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.

Voltage-gated K+ (Kv) channels mediate the flow of K+ across the cell membrane by regulating the conductive state of their activation gate (AG). Several Kv channels display slow C-type inactivation, a process whereby their selectivity filter (SF) becomes less or nonconductive. It has been proposed that, in the fast inactivation-removed Shaker-IR channel, the W434F mutation epitomizes the C-type inactivated state because it functionally accelerates this process. By introducing another pore mutation that prevents AG closure, P475D, we found a way to record ionic currents of the Shaker-IR-W434F-P475D mutant at hyperpolarized membrane potentials as the W434F-mutant SF recovers from its inactivated state. This W434F conductive state lost its high K+ over Na+ selectivity, and even NMDG+ can permeate, features not observed in a wild-type SF. This indicates that, at least during recovery from inactivation, the W434F-mutant SF transitions to a widened and noncationic specific conformation.

Exploratory study on gastrostomy in patients with neurological diseases: usefulness and impact.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a useful intervention for patients with impaired swallowing and a functional gastrointestinal system. Neurological diseases that cause neuromotor dysphagia, brain tumors, and cerebrovascular disease are the most frequent indications; complications are rare, and morbidity and mortality rates are low. OBJECTIVE: To describe the usefulness of PEG in patients with neurological diseases, and its impact on care, survival, and costs and benefits. MATERIAL AND METHODS: We performed a retrospective observational study, reviewing clinical files of patients hospitalised at the National Institute of Neurology and Neurosurgery (years 2015-2017) who underwent PEG placement. RESULTS: The sample included 51 patients: 62.7% were women and the mean (SD) age was 54.4 (18.6) years (range, 18-86). Diagnosis was tumor in 37.3% of cases and cerebrovascular disease in 33.3%. Sixteen patients (33.3%) died and 11 presented minor complications. The PEG tube remained in place for a mean of 9.14 months; in 52.9% of patients it was removed due to lack of improvement and/or tolerated oral intake, with removal occurring after a mean of 5.1 (4.4) months. Among patients' family members, 78.4% reported a great benefit, 43.1% reported difficulty caring for the PEG, and 45.1% reported complicated care in general. The monthly cost of maintaining the PEG was €175.78 on average (range, 38.38-293.45). DISCUSSION AND CONCLUSIONS: This preliminary study reveals that PEG was well indicated in patients with neurological diseases, with survival rates similar to those reported in other studies with long follow-up periods. In patients with cerebrovascular disease, the PEG tube remained in place a mean of 9.14 months, during recovery of swallowing function; however, the cost is high for our population.

Estudio exploratorio sobre gastrostomía en pacientes con enfermedades neurológicas: utilidad e impacto / Exploratory study on gastrostomy in patients with neurological diseases: usefulness and impact

Introducción: La gastrostomía endoscópica percutánea (GEP) es útil para personas con problemas de la vía oral con viabilidad de la vía gástrica. Las enfermedades neurológicas que producen disfagia neuromotora, tumores cerebrales y enfermedad vascular cerebral son las que tienen mayor indicación; las complicaciones son escasas y baja la morbimortalidad. Objetivo: Describir la utilidad de la GEP en pacientes con enfermedades neurológicas y el impacto en el cuidado, sobrevida y coste-beneficio. Material y métodos: Estudio observacional retrospectivo, mediante revisión de expedientes clínicos de pacientes hospitalizados en el Instituto Nacional de Neurología y Neurocirugía (años 2015-2017) que se realizó GEP. Resultados: Se incluyeron 51 pacientes: 62,7% mujeres, edad promedio 54,4 ± 18,6 años (rango; 18 a 86). Diagnósticos: tumor del SNC 37,3% y EVC 33,3%. Mortalidad 33,3% (16 pacientes): 11 presentaron complicaciones menores. Permanencia de la GEP: promedio 9,14 meses. Al 52,9% se le retiró por mejoría y/o toleró la VO, con tiempo promedio 5,1 ± 4,4 meses. El 78,4% de los familiares reportó gran beneficio, el 43,1% percibió difícil el cuidado de la GEP y el 45,1% refirió complicado el cuidado en general. El coste de mantener la GEP mensual fue de 175,78 € en promedio (rango de 38,38 a 293,45 €). Discusión y conclusiones: Este primer estudio revela que la GEP fue bien indicada en pacientes con enfermedades neurológicas, con sobrevida similar a la reportada en otras investigaciones con seguimiento prolongado. En pacientes con EVC la permanencia de la GEP fue de 9,14 meses en promedio, por recuperación de la vía oral; sin embargo, el coste es elevado para nuestra población. (AU)

Introduction: Percutaneous endoscopic gastrostomy (PEG) is a useful intervention for patients with impaired swallowing and a functional gastrointestinal system. Neurological diseases that cause neuromotor dysphagia, brain tumors, and cerebrovascular disease are the most frequent indications; complications are rare, and morbidity and mortality rates are low. Objective: To describe the usefulness of PEG in patients with neurological diseases, and its impact on care, survival, and costs and benefits. Material and methods: We performed a retrospective observational study, reviewing clinical files of patients hospitalised at the National Institute of Neurology and Neurosurgery (years 2015-2017) who underwent PEG placement. Results: The sample included 51 patients: 62.7% were women and the mean (SD) age was 54.4 (18.6) years (range, 18-86). Diagnosis was tumor in 37.3% of cases and cerebrovascular disease in 33.3%. Sixteen patients (33.3%) died and 11 presented minor complications. The PEG tube remained in place for a mean of 9.14 months; in 52.9% of patients it was removed due to lack of improvement and/or tolerated oral intake, with removal occurring after a mean of 5.1 (4.4) months. Among patients’ family members, 78.4% reported a great benefit, 43.1% reported difficulty caring for the PEG, and 45.1% reported complicated care in general. The monthly cost of maintaining the PEG was €175.78 on average (range, 38.38-293.45). Discussion and conclusions: This preliminary study reveals that PEG was well indicated in patients with neurological diseases, with survival rates similar to those reported in other studies with long follow-up periods. In patients with cerebrovascular disease, the PEG tube remained in place a mean of 9.14 months, during recovery of swallowing function; however, the cost is high for our population. (AU)

Impacts of endocrine disrupting chemicals on reproduction in wildlife and humans.

Endocrine disrupting chemicals (EDCs) are ubiquitous in aquatic and terrestrial environments. The main objective of this review was to summarize the current knowledge of the impacts of EDCs on reproductive success in wildlife and humans. The examples selected often include a retrospective assessment of the knowledge of reproductive impacts over time to discern how the effects of EDCs have changed over the last several decades. Collectively, the evidence summarized here within reinforce the concept that reproduction in wildlife and humans is negatively impacted by anthropogenic chemicals, with several altering endocrine system function. These observations of chemicals interfering with different aspects of the reproductive endocrine axis are particularly pronounced for aquatic species and are often corroborated by laboratory-based experiments (i.e. fish, amphibians, birds). Noteworthy, many of these same indicators are also observed in epidemiological studies in mammalian wildlife and humans. Given the vast array of reproductive strategies used by animals, it is perhaps not surprising that no single disrupted target is predictive of reproductive effects. Nevertheless, there are some general features of the endocrine control of reproduction, and in particular, the critical role that steroid hormones play in these processes that confer a high degree of susceptibility to environmental chemicals. New research is needed on the implications of chemical exposures during development and the potential for long-term reproductive effects. Future emphasis on field-based observations that can form the basis of more deliberate, extensive, and long-term population level studies to monitor contaminant effects, including adverse effects on the endocrine system, are key to addressing these knowledge gaps.

Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Comparison between criteria for diagnosing malnutrition in patients with advanced chronic liver disease: GLIM group proposal versus different nutritional screening tools.

BACKGROUND: Different nutritional screening instruments can be used to identify the risk of malnutrition in advanced chronic liver disease patients. The present study aimed to evaluate and compare two nutrition screening tools with the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition in patients with advanced chronic liver disease. METHODS: Two nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002) and Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), were assessed for 166 patients with liver cirrhosis. We compared medium/high nutritional risk screening with the diagnosis of malnutrition, using the GLIM criteria as the reference standard. RESULTS: According to the GLIM criteria, 57.3% of the patients were malnourished. NRS and RFH-NPT identified, respectively, 36.1% and 52.4% of patients with nutritional risk. RFH-NPT presented better agreement with the diagnosis according to GLIM criteria (k = 0.64; 95% confidence interval = 0.52-0.75), higher sensitivity (80%), higher negative predictive value (79%) and larger area under the curve (82.3%) compared to the NRS. CONCLUSIONS: RFH-NPT, when compared with the GLIM method, has substantial agreement in identifying nutritional risk, good sensitivity and good value for diagnosing malnutrition in patients with advanced chronic liver disease.

Activation of stress response axis as a key process in environment-induced sex plasticity in fish.

The determination of sex is an important hallmark in the life cycle of organisms, in which the fate of gonads and then the individual sex are defined. In gonochoristic teleost fish, this process is characterized by a high plasticity, considering that in spite of genotypic sex many environmental factors can cause shifts from one to another molecular pathway, resulting in organisms with mismatching genotypic and phenotypic sexes. Interestingly, in most instances, both female-to-male or male-to-female sex-reversed individuals develop functional gonads with normal gametogenesis and respective progenies with full viability. The study of these mechanisms is being spread to other non-model species or to those inhabiting more extreme environmental conditions. Although water temperature is an important mechanism involved in sex determination, there are other environmental stressors affected by the climate change which are also implicated in stress response-induced masculinization in fish. In this regard, the brain has emerged as the transducer of the environment input that can influence the gonadal fate. Furthermore, the evaluation of other environmental stressors or their synergic effect on sex determination at conditions that simulate the natural environments is growing gradually. Within such scope, the concerns related to climate change impacts rely on the fact that many of biotic and abiotic parameters reported to affect sex ratios are expected to increase concomitantly as a result of increased greenhouse gas emissions and, particularly worrying, many of them are related to male bias in the populations, such as high temperature, hypoxia, and acidity. These environmental changes can also generate epigenetic changes in sex-related genes affecting their expression, with implications on sex differentiation not only of exposed individuals but also in following generations. The co-analysis of multi-stressors with potential inter- and transgenerational effects is essential to allow researchers to perform long-term predictions on climate change impacts in wild populations and for establishing highly accurate monitoring tools and suitable mitigation strategies.

A solid-state integrated photo-supercapacitor based on ZnO nanorod arrays decorated with Ag2S quantum dots as the photoanode and a PEDOT charge storage counter-electrode.

A planar solid-state photocapacitor with two electrodes has been prepared for the first time using a passivated film of ZnS with Ag2S quantum dots deposited on ZnO nanorods, which were electrochemically grown on ZnO seed layers, as the photoanode. The supercapacitor part is composed of a electrodeposited poly(3,4-ethylene-dioxythiophene) PEDOT film as the counter-electrode and an ionic liquid-based electrolyte between them deposited by the dip coating method. The different nanostructures and electrodes were morphologically and structurally characterized, and the device was electrochemically characterized and could reach a potential of 0.33 V during photocharge and a storage efficiency of 6.83%.

Structure, function, and ion-binding properties of a K+ channel stabilized in the 2,4-ion-bound configuration.

Here, we present the atomic resolution crystallographic structure, the function, and the ion-binding properties of the KcsA mutants, G77A and G77C, that stabilize the 2,4-ion-bound configuration (i.e., water, K+, water, K+-ion-bound configuration) of the K+ channel's selectivity filter. A full functional and thermodynamic characterization of the G77A mutant revealed wild-type-like ion selectivity and apparent K+-binding affinity, in addition to showing a lack of C-type inactivation gating and a marked reduction in its single-channel conductance. These structures validate, from a structural point of view, the notion that 2 isoenergetic ion-bound configurations coexist within a K+ channel's selectivity filter, which fully agrees with the water-K+-ion-coupled transport detected by streaming potential measurements.

Exploratory study on gastrostomy in patients with neurological diseases: usefulness and impact. / Estudio exploratorio sobre gastrostomía en pacientes con enfermedades neurológicas: utilidad e impacto.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a useful intervention for patients with impaired swallowing and a functional gastrointestinal system. Neurological diseases that cause neuromotor dysphagia, brain tumors, and cerebrovascular disease are the most frequent indications; complications are rare, and morbidity and mortality rates are low. OBJECTIVE: To describe the usefulness of PEG in patients with neurological diseases, and its impact on care, survival, and costs and benefits. MATERIAL AND METHODS: We performed a retrospective observational study, reviewing clinical files of patients hospitalised at the National Institute of Neurology and Neurosurgery (years 2015-2017) who underwent PEG placement. RESULTS: The sample included 51 patients: 62.7% were women and the mean (SD) age was 54.4 (18.6) years (range, 18-86). Diagnosis was tumor in 37.3% of cases and cerebrovascular disease in 33.3%. Sixteen patients (33.3%) died and 11 presented minor complications. The PEG tube remained in place for a mean of 9.14 months; in 52.9% of patients it was removed due to lack of improvement and/or tolerated oral intake, with removal occurring after a mean of 5.1 (4.4) months. Among patients' family members, 78.4% reported a great benefit, 43.1% reported difficulty caring for the PEG, and 45.1% reported complicated care in general. The monthly cost of maintaining the PEG was €175.78 on average (range, 38.38-293.45). DISCUSSION AND CONCLUSIONS: This preliminary study reveals that PEG was well indicated in patients with neurological diseases, with survival rates similar to those reported in other studies with long follow-up periods. In patients with cerebrovascular disease, the PEG tube remained in place a mean of 9.14 months, during recovery of swallowing function; however, the cost is high for our population.

Linear multimode interference fiber temperature sensor using the liquid in glass thermometer principle.

A temperature sensor based on a multimode interference thermometer is designed and fabricated. The operation mechanism is based on the thermal expansion of a specific volume of ethylene glycol contained in a glass bulb that is connected to a capillary of the same material, with a no-core fiber (NCF) inserted and centered into the capillary tube. As the temperature is increased, the liquid is expanded, and the NCF is gradually covered by the liquid, resulting in a peak wavelength shift that is correlated to the temperature variations. A sensitivity of 0.4447 nm/°C and highly linear response with an R2 of 0.99962 are obtained. The advantage of this configuration is that the sensing temperature range can be adjusted by changing either the inner diameter of the capillary tube or the bulb volume. We can also measure negative temperatures by simply modifying the freezing point of the liquid, which demonstrates the viability of the sensor for many applications.

Utility of neutrophil-to-lymphocyte ratio plus C-reactive protein for infection in systemic lupus erythematosus.

OBJECTIVE: To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE. METHODS: A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%. CONCLUSION: In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.

A new concept of a transparent photocapacitor.

A solid-state transparent photocapacitor has been prepared for the first time by the use of two transparent electrodes (TiO2 and LiFeO2) and also a transparent ion gel-based electrolyte between them, reaching a transmittance of 57% at λ = 555 nm, a specific capacitance of 2.98 µF cm-2 and a specific energy of 0.54 µJ cm-2.