Secondary Fast Breakdown in Narrow Bipolar Events.

The physical mechanism of Narrow bipolar events (NBEs) has been studied for decades but it still holds many mysteries. Recent observations indicate that the fast breakdown discharges that produce NBEs sometimes contain a secondary fast breakdown that propagates back in the opposite direction but this has not been fully addressed so far in electromagnetic models. In this study, we investigate fast breakdown using different approaches that employ a Modified Transmission Line with Exponential decay (MTLE) model and propose a new model, named "rebounding MTLE model," which reproduces the secondary fast breakdown current in NBEs. The model provides new insights into the physics of the fast breakdown mechanism.

Multi-Pulse Corona Discharges in Thunderclouds Observed in Optical and Radio Bands.

How lightning initiates inside thunderclouds remains a major puzzle of atmospheric electricity. By monitoring optical emissions from thunderstorms, the Atmosphere-Space Interactions Monitor (ASIM) onboard the International Space Station is providing new clues about lightning initiation by detecting Blue LUminous Events (BLUEs), which are manifestations of electrical corona discharges that sometimes precedes lightning. Here we combine optical and radio observations from a thunderstorm near Malaysia to uncover a new type of event containing multiple optical and radio pulses. We find that the first optical pulse coincides with a strong radio signal in the form of a Narrow Bipolar Event (NBE) but subsequent optical pulses, delayed some milliseconds, have weaker radio signals, possibly because they emanate from a horizontally oriented electrical discharges which does not trigger full-fledged lightning. Our results cast light on the differences between isolated and lightning-initiating electrical discharges.

Submicrosecond Spectroscopy of Lightning-Like Discharges: Exploring New Time Regimes.

Submicrosecond (0.476 µs per frame with an exposure time of 160 ns) high-resolution (0.38 nm) time-resolved spectra of laboratory-produced lightning-like electrical discharges have been recorded for the first time within the visible spectral range (645-665 nm). The spectra were recorded with the GrAnada LIghtning Ultrafast Spectrograph (GALIUS), a high-speed imaging spectrograph recently developed for lightning research in the IAA-CSIC. Unprecedented spectral time dynamics are explored for meter long laboratory electrical discharges produced with a 2.0 MV Marx generator. The maximum electron density and gas temperature measured in a timescale of ≤0.50 µs (160 ns) were, respectively, ≃1018 cm-3 and ≃32,000 K. Overpressure in the lightning-like plasma channel, black-body dynamics, and self-absorption in spectral lines were investigated.

Long-term response control in a patient with metastatic squamous cell lung cancer after treatment with nivolumab: a case report.

INTRODUCTION: Nivolumab is a fully human programmed death control immune point 1 immune checkpoint inhibitor antibody which promotes antitumor immunity. Cutaneous toxicity associated with nivolumab, immune system related, could be linked to a more durable response in patients with squamous cell lung cancer. CASE REPORT: We present the case of a 62-year-old male diagnosed with metastatic squamous cell lung cancer, who was treated with nivolumab after cytotoxic chemotherapy. After treatment discontinuation, due to grade 2 cutaneous toxicity, the patient is maintaining with durable partial response for more than one year with close follow-up. MANAGEMENT AND OUTCOME: Cumulative doses of nivolumab could cause immunological toxicities that may prolong survival of these patients even after discontinuation of treatment. DISCUSSION: Nivolumab was approved by European Medicines Agency (EMA), as second-line therapeutic, for the treatment of squamous cell lung cancer, showing a median of 9.23 months of overall survival. The development of immune-related skin toxicities has been associated with greater clinical benefit in patients with lung cancer. When cutaneous toxicity forces to nivolumab suspension, in certain cases, the option of not starting again and closely following up the patient may appear reasonable, even though there are no survival data in this context. Suspension of treatment with close monitoring of these patients until progression may be an alternative, since immune-related skin toxicities could be related to a greater clinical benefit and a durable response to nivolumab.

The immune response to Hymenolepis nana in mice decreases tumorigenesis induced by 7,12 dimethylbenz-anthracene.

BACKGROUND: Cancer is a high-impact disease throughout the world. A negative correlation has been established between the development of cancer and the Th2 immune response. Infection by helminth parasites is characterized by the induction of a strong and long-lasting Th2 response. The aim of this work was to evaluate the effect of the immune response induced by the infection with the helminth Hymenolepis nana, on the tumorigenesis induced by dimethylbenz-anthracene (DMBA) in mice. METHODOLOGY: Four different groups of 14 female BALB/c mice were formed; Group A, dimethyl sulfoxide (DMSO) (vehicle) was administered cutaneously, Group B infected with H. nana, group C, cutaneously DMBA and finally Group D infected with H. nana and cutaneous DMBA. The tumor load was determined in those animals that developed cancerous lesions. In all groups were determined: serum concentration of IgE, IFNγ, IL-10, IL-5 and malondialdehyde (MDA). The inflammatory infiltrate was analyzed from skin samples and the expression of the main eosinophilic protein and myeloperoxidase was determined. RESULTS: The group previously infected with H. nana had a reduced amount of tumors with smaller size, in comparison to the group that received only DMBA; this reduction was associated with lower levels of IFNγ and IL-10, while levels of IgE, IL-5 and MDA were higher. Further, the number of eosinophils and neutrophils was statistically higher in the animals that were previously infected with the helminth and developed less tumors. CONCLUSION: The immune response induced by H. nana infection is associated with the reduction of tumors probably due to the activity of eosinophils and neutrophils.

Preferred Management of Primary Deep Arm Vein Thrombosis.

OBJECTIVE: Given its rarity, the management of primary upper extremity deep vein thrombosis is controversial. Although anticoagulation alone is commonly advocated for its treatment, it is unclear if this will reduce the risk of developing post-thrombotic syndrome (PTS). The aim of this "Evidence Driven" Clinical Scenario is to evaluate whether more aggressive treatments (including catheter directed thrombolysis or surgery) might help reduce the risk of PTS or recurrent venous thromboembolism in patients with primary upper extremity deep vein thrombosis (DVT). METHODS: An electronic systematic review of Ovid MEDLINE and Embase was conducted. Randomised controlled trials and observational studies were eligible. The primary outcome was PTS. RESULTS: The initial search identified 146 articles, and 36 more were identified during a secondary search. In total, 25 studies, reporting the outcome of 1271 patients, were included. None of the studies included was a randomised controlled trial and the large majority of studies were retrospective cohorts. The use of anticoagulation alone was associated with a significant risk of PTS. In patients treated with surgery with or without thrombolysis the incidence of PTS was significantly reduced. CONCLUSION: Current evidence, albeit with some methodological limitations, suggests that anticoagulation may not be sufficient to prevent PTS in patients with primary upper extremity DVT and that surgery with or without thrombolysis to repair the anatomical defects is needed.

Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.

BACKGROUND: Mesenchymal stem cells (MSCs) transplantation has become a promising therapeutic choice for musculoskeletal injuries. Joint-related disorders are highly prevalent in horses. Therefore, these animals are considered as suitable models for testing MSC-based therapies for these diseases. The aim of this study was to investigate the clinical and inflammatory responses to intra-articular single and repeat dose administration of autologous or of pooled allogeneic MSCs in healthy equine healthy joints. Six horses were intra-articularly injected with a single autologous dose of bone marrow derived MSCs (BM-MSCs) and two separate doses of allogeneic BM-MSCs pooled from several donors. All contralateral joints were injected with Lactated Ringer's Solution (LRS) as the control vehicle. Signs of synovitis and lameness were evaluated at days 0, 1, 2, 3, 5 and 10 after injection. Total protein (TP), white blood cell count (WBC) and neutrophil count (NC) in synovial fluid were also measured at the same time-points. RESULTS: A mild synovial effusion without associated lameness was observed after all BM-MSCs injections. The second allogeneic injection caused the lowest signs of synovitis. Local temperature slightly increased after all BM-MSCs treatments compared to the controls. TP, WBC and NC in synovial fluids also increased during days 1 to 5 after all BM-MSCs injections. Both, clinical and synovial parameters were progressively normalized and by day 10 post-inoculation appeared indistinguishable from controls. CONCLUSIONS: Intra-articular administration of an allogeneic pool of BM-MSCs represents a safe therapeutic strategy to enhance MSCs availability. Importantly, the absence of hypersensitivity response to the second allogeneic BM-MSCs injection validates the use of repeat dose treatments to potentiate the therapeutic benefit of these cells. These results notably contribute to the development of stem cell based therapies for equine and human joint diseases.

Bayesian robustness in meta-analysis for studies with zero responses.

Statistical meta-analysis is mostly carried out with the help of the random effect normal model, including the case of discrete random variables. We argue that the normal approximation is not always able to adequately capture the underlying uncertainty of the original discrete data. Furthermore, when we examine the influence of the prior distributions considered, in the presence of rare events, the results from this approximation can be very poor. In order to assess the robustness of the quantities of interest in meta-analysis with respect to the choice of priors, this paper proposes an alternative Bayesian model for binomial random variables with several zero responses. Particular attention is paid to the coherence between the prior distributions of the study model parameters and the meta-parameter. Thus, our method introduces a simple way to examine the sensitivity of these quantities to the structure dependence selected for study. For illustrative purposes, an example with real data is analysed, using the proposed Bayesian meta-analysis model for binomial sparse data. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of 1,25(OH)2D3 on BALB/c mice infected with Leishmania mexicana.

The most active metabolite of vitamin D, 1,25(OH)2D3 is a steroid hormone implicated in a wide range of cell functions such as differentiation, proliferation and apoptosis. Leishmania mexicana causes two kinds of cutaneous leishmaniasis: localized or diffuse. In this work we explored the effect of treatment of 1,25(OH)2D3 on a susceptible leishmaniasis mice model. A significant reduction in the lesion size was found in animals treated with 1,25(OH)2D3. Well preserved tissue and presence of large numbers of eosinophils and fibroblasts was found in the group treated with 1,25(OH)2D3. By contrast, destroyed epidermis was observed with large amount of neutrophils and epithelioid macrophages, on infected groups without 1,25(OH)2D3 treatment. The production of pro-inflammatory cytokines in mice infected and treated with 1,25(OH)2D3 was lower than the animals infected without 1,25(OH)2D3 treatment. Interestingly, there were no differences in the number of parasites in both groups. Finally, the amount of collagen was higher in animals with treatment compare with animals without 1,25(OH)2D3 treatment. In summary, mice treated with 1,25 (OH) 2D3 reflect a healing process without elimination of L. mexicana.

Influence of exposure to tobacco cigarette smoke on the eosinophil count in the nasal mucosa of young patients with perennial allergic rhinitis.

BACKGROUND: To assess the influence of exposure to tobacco cigarette smoke on the eosinophil count and the frequency of apoptosis of eosinophils in the nasal mucosa of teenagers with perennial allergic rhinitis. METHODS: Fifty patients were evaluated (aged 10 to 19 years old): 25 patients with and 25 patients with no recent exposure to tobacco cigarette smoke, by means of The Global Youth Tobacco Survey and cotinine/creatinine ratio. After a clinical evaluation, all the patients replied to a validated questionnaire of the severity of nasal symptoms; then, a nasal sample was processed to identify the eosinophil count and the frequency of apoptosis of eosinophils. RESULTS: Patients with active exposure to tobacco cigarette smoke had higher eosinophil counts than patients with no exposure to the smoke. In the two groups, apoptosis of eosinophils in the nasal mucosa was scarce and no significant correlation was observed between the frequency/severity of the nasal symptoms and the eosinophil count. CONCLUSION: Teenagers with perennial allergic rhinitis and active exposure to tobacco cigarette smoke may show increased eosinophil counts in the nasal mucosa, which might not be related to apoptosis of eosinophils or to the frequency/severity of nasal symptoms.

Daily rhythms of blood glucose differ in diurnal and nocturnal European sea bass (Dicentrarchus labrax L.) undergoing seasonal phase inversions.

Sea bass change their feeding rhythms from diurnal to nocturnal in winter, returning to diurnal feeding in spring. Despite behavioral data, the physiological changes that take place during such changes remain unexplored. In this paper, blood glucose rhythms of European sea bass with diurnal/nocturnal self-feeding rhythms were investigated during phase inversions of their feeding behavior (in winter and spring) when both diurnal and nocturnal fish coexist. Blood glucose showed daily variations in both seasons (ANOVA, p < 0.03), fitting a cosine function (COSINOR, p < 0.05) in all cases, except in diurnal fish in spring. The average blood glucose levels of nocturnal fish in winter (2.67 ± 0.09 mmol/l, mean ± SEM) were significantly (t test, p < 0.01) higher than in spring (2.20 ± 0.08 mmol/l), while they were similar (~2.25 mmol/l) in diurnal fish in both seasons. These findings revealed for the first time insights into the seasonal physiological changes that accompany changes in behavioral rhythms in diurnal and nocturnal sea bass.

Exposure to indoor air pollutants (polycyclic aromatic hydrocarbons, toluene, benzene) in Mexican indigenous women.

UNLABELLED: Indoor air pollution is considered to be a serious public health issue in Mexico; therefore, more studies regarding this topic are necessary. In this context, we assessed exposure to polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds in: (i) women who use firewood combustion (indoor) for cooking and heating using traditional open fire; (ii) women who use firewood combustion (outdoor) for cooking and heating using traditional open fire; and (iii) women who use LP gas as the principal energy source. We studied 96 healthy women in San Luis Potosi, México. Urine samples were collected, and analyses of the following urinary exposure biomarkers were performed by high-performance liquid chromatography: 1-hydroxypyrene (1-OHP), trans, trans-muconic acid, and hippuric acid (HA). The highest levels of 1-OHP, trans, trans-muconic acid, and HA were found in communities where women were exposed to indoor biomass combustion smoke (or products; geometric mean ± s.d., 3.98 ± 5.10 µmol/mol creatinine; 4.81 ± 9.60 µg/l 1-OHP; 0.87 ± 1.78 mg/g creatinine for trans, trans-muconic acid; and 1.14 ± 0.91 g/g creatinine for HA). Our findings indicate higher exposure levels to all urinary exposure biomarkers studied in women who use indoor firewood combustion for cooking and heating (using traditional open fire). PRACTICAL IMPLICATIONS: High mean levels of 1-hydroxypyrene, t,t-muconic acid, and hippuric acid were found in women who use firewood combustion (indoor) for cooking and heating using traditional open fire and taking into account that millions of women and children in Mexico are living in scenarios similar to those studied in this report, the assessment of health effects in women and children exposed to polycyclic aromatic hydrocarbons and volatile organic compounds is urgently needed. Moreover, it is immediately necessary an intervention program to reduce exposure.

Does feeding time affect fish welfare?

Increased aquaculture production has raised concerns about managing protocols to safeguard the welfare of farmed fish, as consumers demand responsible aquaculture practices to provide 'welfare friendly' products. Feeding is one of the largest production cost in a fish farm and can be one of the biggest stressors for fish. Under farming conditions, fish are challenged with artificial diets and feeding regimes, and inadequate feeding conditions cause stress, alteration of normal behavioural patterns, poor performance and eventually diseases and death, which are by no means acceptable neither economically nor ethically. This review aims to highlight the impact of feeding rhythms and feeding time upon physiological and behavioural welfare indicators, which show circadian rhythms as well. Therefore, all these variables should be considered when designing feeding strategies in farming conditions and assessing the welfare state of cultured fish.

Global Distribution of Key Features of Streamer Corona Discharges in Thunderclouds.

We present nighttime worldwide distributions of key features of Blue LUminous Events (BLUEs) detected by the Modular Multispectral Imaging Array of the Atmosphere-Space Interaction Monitor. Around 10% of all detected BLUEs exhibit an impulsive single pulse shape. The rest of BLUEs are unclear (impulsive or not) single, multiple or with ambiguous pulse shapes. BLUEs exhibit two distinct populations with peak power density <25 µWm-2 (common) and ≥25 µWm-2 (rare) with different rise times and durations. The altitude (and depth below cloud tops) zonal distribution of impulsive single pulse BLUEs indicate that they are commonly present between cloud tops and a depth of ≤4 km in the tropics and ≤1 km in mid and higher latitudes. Impulsive single pulse BLUEs in the tropics are the longest (up to ∼4 km height) and have the largest number of streamers (up to ∼3 × 109). Additionally, the analysis of BLUEs has turned out to be particularly complex due to the abundance of radiation belt particles (at high latitudes and in the South Atlantic Anomaly [SAA]) and cosmic rays all over the planet. True BLUEs can not be fully distinguished from radiation belt particles and cosmic rays unless other ground-based measurements associated with the optically detected BLUEs are available. Thus, the search algorithm of BLUEs presented in Soler et al. (2021), https://doi.org/10.1029/2021gl094657 is now completed with a new additional step that, if used, can considerably smooth the SAA shadow but can also underestimate the number of BLUEs worldwide.

Effects of cadmium on locomotor activity rhythms of the amphipod Gammarus aequicauda.

Behavioural responses are linked to complex biochemical and physiologic changes and may act as sensitive indicators of the sublethal effects of pollutants. This article investigates changes in the locomotor activity rhythms of the amphipod Gammarus aequicauda exposed to cadmium (Cd) as a model to study the effect of pollutants on an ecologically important species. Under a 12:12 h light-to-dark cycle, G. aequicauda showed a strict nocturnal rhythm, with 90.2±0.4% of their total daily activity occurring during the night. Under constant darkness, circadian rhythms persisted for 10 days, with a mean periodicity of 24.32 h, thus confirming endogenous control. Exposure to sublethal concentrations of Cd (0.16, 0.20, 0.24, and 0.28 mg l(-1)) did not change the nocturnal activity patterns of G. aequicauda, although their swimming activity during the night was significantly decreased by exposure to concentrations of 0.24 and 0.28 mg Cd l(-1). In conclusion, locomotor activity bioassays using the amphipod G. aequicauda appeared to be a sensitive indicator of Cd contamination, and sensitivity and tolerance to Cd in short-term bioassays may depend on the time of the day tests are carried out. These results provide further support for the idea that behavioural end points in amphipods are useful indicators of pollutant exposure and that future studies should take circadian rhythms into consideration.

Outcomes in patients with acute pulmonary embolism and patent foramen ovale: Findings from the RIETE registry.

INTRODUCTION: An increased risk of ischemic stroke in patients with acute pulmonary embolism (PE) and patent foramen ovale (PFO) was reported but few data exist regarding prognostic outcomes of those patients. MATERIAL AND METHODS: Using data in the RIETE registry, we compared the characteristics, therapeutic approaches and outcomes of patients with PE according to the presence or absence of PFO. RESULTS: From August 2016 to January 2020, 4148 patients with acute PE were enrolled. Of these, 2775 (67%) had no transthoracic echocardiogram (TTE), 993 (24%) underwent TTE but had no reported results on PFO. Among the remaining 380 patients, 287 (74%) did not have PFO and 93 (26%) had PFO. Patients with PFO were more likely to have chronic heart failure, prior myocardial infarction or ischemic stroke than those without PFO. Patients with PFO had a higher rate of subsequent ischemic stroke than those without PFO (hazard ratio (HR): 9.28; 95% CI: 1.83-69.1), than those with TTE but no data on PFO (HR: 10.1; 95% CI: 2.56-42.4) or without TTE (HR: 9.78; 95% CI: 3.02-28.4). On multivariable analysis, patients with PFO were at increased risk for subsequent ischemic stroke than those without PFO (HR: 8.96; 95% CI: 1.68-47.7). CONCLUSIONS: PFO was searched in a minority of patients with an acute PE in real life setting. Subject to possible selection and measurement biases, our results confirmed a higher risk of ischemic stroke in PE patients with PFO compared to those without PFO. This association warrants further investigation before determining the best therapeutic option in patients with acute PE and concomitant PFO.

Health risk assessment in children living in an urban area with hydrofluorosis: San Luis Potosí Mexico case study.

BACKGROUND: Fluoride is an inorganic element, which can be found in high concentrations in groundwater. Its consumption and exposure have consequences on human health. The objective of this study was to evaluate fluoride exposure and develop a health risk assessment in children from an urban area with hydrofluorosis in Mexico. METHODS: Water fluoride levels in active wells were provided by the Water State Agency and divided into three zones: agriculture zone (Zone A), metallurgical zone (Zone B), and industrial zone (Zone C). Urinary fluoride levels were determined by potentiometric method using an ion-selective electrode. Health risk assessment was performed through Monte Carlo model analysis and hazard quotient was calculated. RESULTS: According to fluoride well concentration, all zones have high concentration especially Zone B (2.55 ± 0.98 mg/L). Urinary fluoride concentrations were highest in children in Zone B (1.42 ± 0.8 mg/L). The estimated median daily intake dose of fluoride was 0.084 mg/Kg-day for the children living in zone B. The highest mean HQ value was to Zone B (1.400 ± 0.980), followed by Zone C (0.626 ± 0.443). CONCLUSION: The levels of fluoride exposure registered are a potential risk to generate adverse health effects in children in the San Luis Potosi metropolitan area.

Daily rhythms of locomotor activity, feeding behavior and dietary selection in Nile tilapia (Oreochromis niloticus).

Fish do not feed at any time of the day and on whatever food item they encounter in the wild, but they show daily rhythms of feeding activity and dietary selection. The aim of this research was to investigate the daily rhythms of behavior in Nile tilapia self-fed with plant-based diets supplemented with different levels of exogenous phytase (an enzyme that hydrolyzes non-digestible phytate and improves the nutritional value of the diet). To this end, ten males were individually kept in 50-L tanks, each equipped with two self-feeders and one infrared photo-cell connected to a computer. The selection factors investigated were the level of phytase supplementation (0 IU kg(-1) vs 1500 IU kg(-1); 1500 IU kg(-1) vs 4000 IU kg(-1)) or sodium phytate (1% phytate vs 1% phytate+1500 IU kg(-1) phytase). The results revealed that 66.7% of total daily activity occurred during the day, while feeding was strictly nocturnal, with 93.0% of the daily food demands occurring at night. Tilapia preferred the diet with 1500 IU kg(-1) phytase rather than the control or 4000 IU kg(-1) diets. When exogenous sodium phytate was added to the diet, tilapia preferred the phytase diet. In conclusion tilapia self-feed at night (although locomotor activity was mostly diurnal) and chose plant-diets containing phytase, which should be taken into account when designing feeding strategies and practical diets for tilapia aquaculture.

[Dosage of presurgical cefazolin in obese and non-obese patients. Does weight matter?] / Dosificación de cefazolina prequirúrgica en pacientes obesos y no obesos. ¿Importa el peso?

OBJECTIVE: Evaluation of the effectiveness of a standard dose of cefalozin 2 grams for surgical site infection (SSI) prevention in obese patients compared to non-obese patients. There is no still controversy surrounding which is the best dosage of this antibiotic in obese patients for surgical prophylaxis. METHODS: Retrospective review of men who received prophylactic cefazolin between January 1st, 2019 and June 30th, 2019 in a traumatology department of a university hospital. Patients were stratified into 2 groups: obese (≥ 100 kg and body mass index (BMI)> 30 kg / m2) and non-obese. Patients without a 90 days follow-up after surgery and/or with an active infection at the time of surgery and/or treated with immunosuppressants were excluded. Demographic data, height, real weight, smoking, diabetes, concomitant use of immunosuppressants, surgery data and presence of infection until day 90 were collected. RESULTS: A total of 57 patients underwent traumatic surgery with prophylactic cefazolin, 26 non-obese and 23 obese, were studied. Both groups presented statistically significant differences in weight, BMI and post-surgery use of cefazolin. No significant differences were observed in the other variables. Two obese (8.7%) and two non-obese (7.7%) patients developed SSIs after 63 days post-surgery on average, following the difference between the groups being statistically non-significant. CONCLUSIONS: This study shows that there is no significant difference in SSI with a standard prophylactic dose of two grams of cefazolin between obese and non-obese patients.