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Se analiza la ultraestructura de Allonothrus neotropicus con ejemplares recolectados en hojarasca de suelo de la región Caribe de Costa Rica. Los caracteres que definen esta especies son: 1) seta e1 el doble de larga que la seta d1, 2) seta e1 con la misma longitud que la distancia entre las setas e1- h1, 3) seta d2 1.5 X más larga que de la seta d1, 4) ausencia de cavidad oval en la sección distal del notogaster, 5) forma del notogaster ovalada, 6) superficie de las setas adanales 1 y 2 ciliada, 7) longitud 582 μm. En la deutoninfa las setas le son tan largas como los sensilos que presentan el mismo ensanchamiento distal que los adultos. Las setas e1 son mayores que las setas d2, las setas c1, d1, y d2 son similares en desarrollo. La distancia entre la seta e1- h1 es de dos veces la longitud de la seta e1. Los tarsos son monodáctilos a diferencia del adulto. La placa genital presenta solo 7 pares de setas. Las placas anales y adanales presentan poco desarrollo. La longitud total de la deutoninfa es de 391 μm. Es notable la diferencia de tamaño registrada entre los especímenes adultos de México y Bolivia (617-658 μm) y los de Costa Rica (479 μm); los cuales presentan una reducción de tamaño de entre 20 y 30% respecto a los especímenes de México y Bolivia. La mayoría de los caracteres considerados diagnósticos de la especie se hallan bien definidos, excepto la longitud corporal y la distancia entre las setas e1-h1. The ultrastructure of Allonothrus neotropicus is studied with specimens collected in soil with leaf litter in the Caribbean region of Costa Rica. The characters that define this species are: 1) seta e1 twice the length of seta d1, 2) seta e1 with the same length as the distance between the setae e1- h1, 3) seta d2 half the length of seta d1, 4) absence of oval cavity in the distal section of notogaster, 5) notogaster oval-shaped, 6) surface of the adanal setae 1 and 2 ciliated, 7) body length 582 μm. In deutonynph, setae le are as long as the sensillae with the same distal club present in adults. Setae e1 are higher than setae d2, setae c1, d1 and d2 with similar development. Distance between e1- h1 twice the length of e1. Tarsal claws in monodactylous are different from the adult. Genital plate has only seven pairs of setae. Anal and adanal plates are weakly developed. The total length of deutonynmph is 391 μm. It is remarkable the size difference observed between specimens of México and Bolivia (617-658 μm) and Costa Rica (479 μm), with size 20 to 30% less than the Mexican and Bolivian specimens. Most of the diagnostic characters of the species are well defined, except the body length and the distance between e1- h1. [ABSTRACT FROM AUTHOR]

In this paper, the species concept within genus Elaphrothrips is discussed, as well as problems of taxonomic criteria related to this group. In addition, the morphological variations and the characteristics of the species groups that occur in the genus, are also discussed. Furthermore, specimens of Elaphrothrips sampled in Costa Rica which belong to the collection of the Senckenberg Museum Frankfurt, Germany, were studied and three new species were found and described. [ABSTRACT FROM AUTHOR]

Isla del Coco is an oceanic island 500km off the Pacific coast of Costa Rica. It is a National Park and its marine fauna has been relatively well protected. The island is famous for its elasmobranch (sharks, rays and skates) sightings in shallow waters. Here we present a catalogue of the deepwater elasmobranchs observed with the DeepSee submersible. Five species of sharks, six species of skates and one ray have been observed between 45 and 330m depth. Triaenodon obesus, the white tip reef shark, was commonly observed between 80 and 301m, but only in the afternoons. Sphyrna lewini, the scalloped hammerhead shark, was observed as deep a 303m, but commonly between 45 and 90m, and close to the island. Odontaspis ferox, the smalltooth sand tiger shark, was observed between 82 and 316m. Echinorhinus cookei, the prickly shark, was observed between 91 and 320m. Rhincodon typus, the whale shark, was observed only close to the island, between 77 and 80m. Taeniura meyeni, the marbled ray, was observed only close to the island, between 45 and 90m. A Dasyatis sp., similar to the the diamond stingray, was observed only once close to the island at 60m; this is the first report of this genus at Isla del Coco National Park. Manta birostris, the giant manta, was only observed close to the island at 90m. Mobula tarapacana, the sicklefin devil ray, was observed between 60 and 326m, extending its maximum depth almost 10 times what has been reported. Aetobatus narinari, the spotted eagle ray, was observed only close to the island between 60 and 82m. Torpedo peruana, the Peruvian torpedo ray, was observed only once at 313m, and is the first record of this species from Isla del Coco National Park. [ABSTRACT FROM AUTHOR]

Atmospheric monitoring is one of the fundamental steps in identifying strategies to minimize, prevent and control the impact of the dispersion of pollutants in the air, on public health and the environment. Therefore, the main objective of this article is to propose a methodology for selecting air monitoring sites in urban areas affected by emissions from mobile sources. First, the places with the highest vehicular flow were identified and prioritized according to the following selection criteria: safety, influence of other sources, ease of assembly of equipment, accessibility to the site, identification of barriers and obstacles, historical record of data and degree concentration of the pollutant: in this case carbon monoxide, using CALINE 3 software. The modeling grouped characteristic data related with roads, meteorology and vehicular flow of a typical year of the zone under study. A quantitative assessment is assigned to each of these parameters, which defines the sites where the monitoring will be performed. As a result, it was developed a guide to select those places where atmospheric monitoring campaigns related with mobile sources can be held. This methodology was applied in the city of Cartagena de Indias by using air quality model for assessment, CALINE 3. [ABSTRACT FROM AUTHOR]

Background: Providing quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the 'Golden Hour' intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital., Methods: A comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario "Dr. José Eleuterio González" was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative 'Mexico in Alliance with St. Jude' project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups., Results: A total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7 % of the pre-intervention group received the first dose of antibiotics within 60 min of presenting to the emergency department compared to 84.6 % in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 min, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6 % to 2.3 % (p-value = 0.03)., Conclusions: Sustainability of the quality improvement project 'Golden Hour' in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation., Competing Interests: Conflicts of interest None., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since β-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus β-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and β-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of β-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K + ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with β-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

A syringe for the long-term, room-temperature storage and injection of vaccines is described. Stabilisation was achieved by drying from a trehalose-containing buffer which formed an inert soluble glass distributed in the internal interconnected voids in an absorbent, compliant, reticulated, medical-grade, porous sponge. The sponge is stored inside the barrel of a syringe and the vaccines are re-solubilised by the aspiration of water. The syringe contains the sponge throughout the filling and drying processes in manufacture, and in transport, stockpiling and finally injection. The active vaccine is delivered to the patient in the normal injection process by depressing the plunger, which compresses the sponge to completely expel the dose. Full recovery of vaccine potency, after 7-10 months @ 45 °C, was shown by complete protection against supra-lethal doses of active toxins in immunised Guinea pigs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employed by either Stablepharma Spain SL or Stablepharma Ltd., (Copyright © 2023 Stablepharma Ltd, 4 Queen St, Bath, BA1 1HE, UK. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To report a case of primary breast B-cell non-Hodgkin’s lymphoma (PBL) and to conduct a literature review of its diagnosis and treatment., Materials and Methods: Case report of an 80-year-old female patient who presented to a private referral institution in Mexico, with PBL. She was also diagnosed with primary liver melanoma by means of targeted biopsy and pathology testing. The patient received treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), quadrantectomy, lymph node dissection and radiotherapy. The PBL showed good response but, because of progression of the second primary tumor, the patient went on to receive palliative care. A review of the literature was conducted in Medline via PubMed, LILACS and Google Scholar. Cohort studies, case reports and case series in patients with PBL that discussed diagnosis, treatment and prognosis of this disease, published in English and Spanish between 2000 and 2022, were included., Results: Overall, 23 titles were identified, of which 17 consisting of case reports and case series met the inclusion criteria. The majority of patients received R-CHOP as chemotherapy regimen, with irradiation as adjunct therapy. Close to 80 % went into complete remission. The most frequent site of recurrence was the central nervous system. Five-year survival was 83.6 % in the included studies., Conclusions: At present, the CHOP regimen, with or without rituximab and usually accompanied by radiotherapy, is the most widely used and the only one that has shown a positive impact on survival. Additional randomized clinical trials are needed in order to gain a clearer insight into the effectiveness and safety of these treatments.

We propose a mathematical model based in ordinary differential equations between bacterial pathogen and Bacteriophages to describe the infection dynamics of these populations, for which we use a nonlinear function with an inhibitory effect. We study the stability of the model using the Lyapunov theory and the second additive compound matrix and perform a global sensitivity analysis to elucidate the most influential parameters in the model, besides we make a parameter estimation using growth data of Escherichia coli (E.coli) bacteria in presence of Coliphages (bacteriophages that infect E.coli ) with different multiplicity of infection. We found a threshold that indicates whether the bacteriophage concentration will coexist with the bacterium (the coexistence equilibrium) or become extinct (phages extinction equilibrium), the first equilibrium is locally asymptotically stable while the other is globally asymptotically stable depending on the magnitude of this threshold. Beside we found that the dynamics of the model is particularly affected by infection rate of bacteria and Half-saturation phages density. Parameter estimation show that all multiplicities of infection are effective in eliminating infected bacteria but the smaller one leaves a higher number of bacteriophages at the end of this elimination.

Recently, nanotechnology and nanoparticles (NPs) such as AgNPs and AuNPs have become important in analytical chemistry due to their great potential to improve the performance of electrochemical sensors. In this work, Ag and Au nanoparticles have been synthesized using a green route in which a grape stalk waste extract is used as a reducing agent to obtain metallic nanoparticles. These NPs were used to customize the surface of commercial screen-printed electrodes (SPCNFEs). The spin-coating method was used to modify commercial SPCNFEs under a nitrogen atmosphere. The resulting electrodes were used in a determination study of Cd(II), Pb(II), and U(VI) with differential pulse anodic stripping voltammetry (DPASV). The customized green AgNPs and AuNPs electrodes presented higher sensitivity and electroanalytical performance than the non-modified SPCNFE. The results showed that the best analytical parameters were obtained with the green, silver nanoparticle SPCNFEs, with a LOD of 0.12 μg L -1 for Pb(II), which is a lower value compared to the most restrictive regulation guidelines. Additionally, the U(VI) ion was successfully determined using the developed G-AgNPs-SPCNFE in spiked tap water, showing comparable results with the ICP-MS technique.

Background: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD)., Methods: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial. Patients aged ≥50 years, with clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12-25 were randomized (1:1) to receive masitinib 4.5 mg/kg/day (administered orally as two intakes) or placebo. A second, independent parallel group (distinct for statistical analysis and control arm), randomized patients (2:1) to masitinib at an initial dose of 4.5 mg/kg/day for 12 weeks that was then titrated to 6.0 mg/kg/day, or equivalent placebo. Multiple primary outcomes (each tested at a significance level of 2.5%) were least-squares mean change from baseline to week 24 in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), or the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL). Safety for each masitinib dose level was compared against a pooled placebo population., Results: Masitinib (4.5 mg/kg/day) (n=182) showed significant benefit over placebo (n=176) according to the primary endpoint of ADAS-cog, -1.46 (95% CI [-2.46, -0.45]) (representing an overall improvement in cognition) versus 0.69 (95% CI [-0.36, 1.75]) (representing increased cognitive deterioration), respectively, with a significant between-group difference of -2.15 (97.5% CI [-3.48, -0.81]); p<0.001. For the ADCS-ADL primary endpoint, the between-group difference was 1.82 (97.5% CI [-0.15, 3.79]); p=0.038 (i.e., 1.01 (95% CI [-0.48, 2.50]) (representing an overall functional improvement) versus -0.81 (95% CI [-2.36, 0.74]) (representing increased functional deterioration), respectively). Safety was consistent with masitinib's known profile (maculo-papular rash, neutropenia, hypoalbuminemia). Efficacy results from the independent parallel group of titrated masitinib 6.0 mg/kg/day versus placebo (n=186 and 91 patients, respectively) were inconclusive and no new safety signal was observed., Conclusions: Masitinib (4.5 mg/kg/day) may benefit people with mild-to-moderate AD. A confirmatory study has been initiated to substantiate these data., Trial Registration: EudraCT: 2010-021218-50., Clinicaltrials: gov : NCT01872598., (© 2023. The Author(s).)

Context: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified., Objective: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action., Materials and Methods: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound., Results: ( E )-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum , afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED 50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM., Conclusions: ( E )-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum , was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle .

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K + ) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K + homeostasis, and we review the effects of dietary K + on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K + secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.

We presented a strategy for enhancing the sensitivity of terahertz glucose sensing with a hydrogel platform pre-embedded with Au nanoparticles. Physiological-level glucose solutions ranging from 0 to 0.8 mg/mL were measured and the extracted absorption coefficients can be clearly distinguished compared to traditional terahertz time domain spectroscopy performed directly on aqueous solutions. Further, Isotherm models were applied to successfully describe the relationship between the absorption coefficient and the glucose concentration (R 2  = 0.9977). Finally, the origin of the sensitivity enhancement was investigated and verified to be the pH change induced by the catalysis of Au nanoparticles to glucose oxidation., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.

Competing Interests: Competing interests: We have read and understood BMJ policy on competing interests and have the following to declare: none.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug-drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56-320 mg/kg), antiallodynic (100-562 mg/kg), and antihyperalgesic and anti-inflammatory (10-178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Novel sensing technologies proposed must fulfill the demands of wastewater treatment plants, the food industry, and environmental control agencies: simple, fast, inexpensive, and reliable methodologies for onsite screening, monitoring, and analysis. These represent alternatives to conventional analytical methods (ICP-MS and LC-MS) that require expensive and non-portable instrumentation. This needs to be controlled by qualified technicians, resulting moreover in a long delay between sampling and high-cost analysis. Electrochemical analysis based on screen-printed electrodes (SPEs) represents an excellent miniaturized and portable alternative due to their disposable character, good reproducibility, and low-cost commercial availability. SPEs application is widely extended, which makes it important to design functionalization strategies to improve their analytical response. In this sense, different types of nanoparticles (NPs) have been used to enhance the electrochemical features of SPEs. NPs size (1-100 nm) provides them with unique optical, mechanical, electrical, and chemical properties that give the modified SPEs increased electrode surface area, increased mass-transport rate, and faster electron transfer. Recent progress in nanoscale material science has led to the creation of reproducible, customizable, and simple synthetic procedures to obtain a wide variety of shaped NPs. This mini-review attempts to present an overview of the enhancement of the electrochemical response of SPEs when NPs with different morphologies are used for their surface modification.

The Covid-19 and other recent pandemics has highlighted existing weakness in health systems across the Latin-America and the Caribbean (LAC) region to effectively prepare for and respond to Public Health Emergencies. It has been stated that quality of care will be among the most influential factors on Covid 19 mortality rates and low systems performance is the common case in these countries. More comprehensive and system level strategies are required to address the challenges. These must focus on redesigning and strengthening health systems to make them more resilient to the changing needs of populations and based on quality improvement methods that have shown rigorously evaluated positive effects in previous local and regional experiences. A call to action is being made by the Latin American Consortium for Quality, Patient Safety and Innovation (CLICSS) and they provide specific recommendations for decision makers., (© The Author(s) 2020. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED 30 ) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (C max ) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED 30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was C max for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.

Diatoms are one of the most abundant, diverse and ecologically relevant phytoplanktonic group, contributing enormously to global biogeochemical processes like the carbon and silica cycles. This large success has been partly attributed to the mechanical and optical properties of the silica shell (the frustule) that envelops their body. But since they lack motility it is difficult to conceive how they cope with the fast-fluctuating environment they live in and where distributions of resources are very heterogeneous and dynamical. This pinpoints an important but yet poorly understood feature of diatoms physiology: buoyancy regulation that helps them controlling their sinking speed and position in the water column. While buoyancy regulation by light and nutrients availability has been well studied, the effect of hydromechanical stress via fluid shear has been rather overlooked when considering diatoms dynamics. Here, we aim to start filling this gap by first presenting direct experimental evidences for buoyancy control in response to hydro-mechanical stress and then review recent theoretical models where simple couplings between local shear and buoyancy control always result in heterogeneous cell distributions, specific accumulation regions within complex flows and increased sedimentation times to the depths, features of direct ecological relevance. We conclude by suggesting future experiments aiming to unveil such coupling and therefore gain better understanding on the fate of these fascinating microorganisms in their natural habitat. This article is part of the theme issue 'Stokes at 200 (part 2)'.

The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue 'Stokes at 200 (part 2)'.

Mixing fluids often involves a periodic action, like stirring one's tea. But reciprocating motions in fluids at low Reynolds number, in Stokes flows where inertia is negligible, lead to periodic cycles of mixing and unmixing, because the physics, molecular diffusion excepted, is time reversible. So how can fluid be mixed in such circumstances? The answer involves a geometric phase. Geometric phases are found everywhere in physics as anholonomies, where after a closed circuit in the parameters, some system variables do not return to their original values. We discuss the geometric phase in fluid mixing: geometric mixing. This article is part of the theme issue 'Stokes at 200 (part 2)'.

Introduction: The hypothesis of an association between papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) continues to generate debate. Retrospective studies suggest that there is a greater probability of diagnosing a PTC in surgical specimens with CLT; however, prospective studies suggest that there is no true increase in risk., Methods: An analytical, cross-section measurement and retrospective study was carried out considering gender, age and diagnosis of CLT and PTC in surgical specimens. A binary logistic regression model was proposed to predict the probability of carrying out the diagnosis of PTC based on the diagnosis of CLT, gender and age., Results: The study population consisted of 1136 patients, 1047 (92.2%) women and 89 (7.8%) men, with an average age of 47.5±14.3 years. The prevalence of CLT and PTC was 14.9% and 16.1% respectively. Coexistence between PTC and CLT was found in 44 patients, corresponding to 3.9% of the population. Our logistic regression model suggests that the probability of diagnosing PTC in surgical specimens of male patients under 40 years old and with CLT is 53.8%., Conclusions: We suggest that there is a greater probability of diagnosing PTC in surgical specimens with confirmatory histological data for CLT; in addition, in males under 40 years old this probability increases., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Carbon-nanofiber-based screen-printed electrodes modified with silver nanoparticles (Ag-NP-SPCNFEs) were tested in a pioneering manner for the direct determination of As(V) at low μg L -1 levels by means of differential pulse anodic stripping voltammetry. Screen-printed electrodes were modified with two different types of Ag-NPs, nanoseeds (NS), and nanoprisms (NPr) and characterized both microscopically and electrochemically. Furthermore, after optimizing the direct voltammetric determination of As(V), the analytical performance of considered sensors was compared for the direct determination of As(V). These results suggest that Ag-NS offer a better analytical response compared to Ag-NPr, with a detection and quantification limit of 0.6 and 1.9 µg L -1 , respectively. The proposed methodology was validated using a spiked tap water sample with a very high reproducibility and good agreement with inductively coupled plasma - mass spectrometry (ICP-MS) measurements.

The incorporation of nanomaterials on (bio)sensors based on composite materials has led to important advances in the analytical chemistry field due to the extraordinary properties that these materials offer. Nanodiamonds (NDs) are a novel type of material that has raised much attention, as they have the possibility of being produced on a large scale by relatively inexpensive synthetic methodologies. Moreover, NDs can present some other interesting features, such as fluorescence, due to surface functionalization and proved biocompatibility, which makes them suitable for biomedical applications. In addition, NDs can be customized with metallic nanoparticles (NPs), such as silver or gold, in order to combine the features of both. Raw NDs were used as modifiers of sensors due to the electrocatalytic effect of the sp 2 and oxygenated species present on their surface. The aim of this research work is evaluating the applicability of NDs modified with silver (Ag@NDs) and gold (Au@NDs) nanoparticles for the development of a suitable (bio)sensing platform. A complete morphological and electrochemical characterization as a function of the prepared nanocomposite composition was performed in order to improve the electroanalytical properties of the developed (bio)sensors. In the present work, the optimal composition for Au@NDs present on the nanocomposite matrix is 3.5% and the one for Ag@NDs is 1%. Good results were obtained in the evaluation of the optimal composition towards hydrogen peroxide and glucose as a model analyte using a (bio)sensor based on graphite-epoxy-Ag@NDs (17:82:1).

Peptic ulcer disease, the most common gastrointestinal disorder, is currently treated with several types of drugs, but all have severe side effects. The aim of the present study was to evaluate the gastroprotective activity of juanislamin, isolated from Calea urticifolia , in a rat model of ethanol-induced gastric lesions. Thirty minutes after orally administering a given dose of juanislamin (from 1 to 30 mg/kg) or carbenoxolone (the reference drug, at 1-100 mg/kg) to rats, 1 mL of ethanol was applied, and the animals were sacrificed 2 h later. The stomachs were removed and opened to measure the total area of lesions in each. To examine the possible participation of prostaglandins, nitric oxide and/or sulfhydryl groups in the mechanism of action of juanislamin, the rats received indomethacin, NG-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or N -ethylmaleimide pretreatment, respectively, before being given juanislamin and undergoing the rest of the methodology. Juanislamin inhibited gastric lesions produced by ethanol in a non-dose-dependent manner, showing the maximum gastroprotective effect (100%) at 10 mg/kg. The activity of juanislamin was not modified by pretreatment with indomethacin, l-NAME or N -ethylmaleimide. In conclusion, juanislamin protected the gastric mucosa from ethanol-induced damage, and its mechanism of action apparently does not involve prostaglandins, nitric oxide or sulfhydryl groups.

Background: As the time this data was studied in Florida, USA was expecting a surge in number of COVID patients. We are hereby presenting analysis of clinical data collected from the first 30 COVID positive patients admitted to our teaching hospital in Sarasota Florida., Methods: The present study was conducted at a not-for-profit 839-bed level-2 regional trauma center, level-3 neurointensive intensive care unit (ICU), and comprehensive stroke and cardiovascular center located on Florida's Central Gulf Coast. It was a single-center, retrospective review of the first 30 patients with reverse transcriptase-polymerase chain reaction confirmed 2019-nCoV infection between March and April 2020. Deidentified patient demographic data, abnormal admission laboratory and radiology findings, treatment medications received, need for mechanical ventilation, complications, and final outcome were recorded., Results: A total of 30 patients were included who were admitted during the study period. Majority of the patients (86%) were elderly, males were 57%, and the average age was 70 years (range, 38-90). About 43% had any travel history outside the region and most (83%) had a comorbidity. Fever, cough, and shortness of breath were common presenting symptoms. About 33% of the patients required ICU at presentation. Abnormal imaging on presentation was present in 80% of the patients and 42% of them had nonspecific bilateral opacities. Complications seen included acute hypoxic respiratory failure (43%), renal failure (13%), septic shock (10%), cytokine storm (3%), and cardiomyopathy (3%). All nonsurvivors developed acute respiratory distress syndrome prior to death. Of the survivors, 21 (70%) were relieved and were discharged., Conclusion: The most common presenting symptoms included fever, cough, and shortness of breath. Patients who required ICU admission at presentation had a worse prognosis. Those with greater severity of symptoms were mainly elderly patients among which the most common comorbidity was hypertention followed by cardiac disease., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Emergencies, Trauma, and Shock.)

Quality Problem: The incidence of central line-associated bloodstream infections (CLABSI) in Latin America has been estimated at 4.9 episodes per 1000 central line (CL) days, compared to a pooled incidence of 0.9 in the United States. CLABSI usually result from not adhering to standardized health procedures and can be prevented using evidence-based practices., Initial Assessment: The first phase of the 'Adiós Bacteriemias' Collaborative was implemented in 39 intensive care units (ICUs) from Latin America from September 2012 to September 2013 with a 56% overall reduction in the incidence of CLABSI., Choice of Solution: Bundles of care for the processes of insertion and maintenance of CLs have proven to be effective in the reduction of CLABSI across different settings., Implementation: Building on the results of the first phase, we implemented a second phase of the 'Adiós Bacteriemias' Collaborative between June 2014-July 2015. We adapted the Breakthrough Series (BTS) Collaborative model to guide the adoption of bundles of care for CLABSI prevention through virtual learning sessions and continuous feedback., Evaluation: Eighty-three ICUs from five Latin American countries actively reported process and outcome measures. The overall reduction in the CLABSI incidence rate was 22% (incidence rate 0.78; 95% CI 0.65, 0.95), from 2.58 episodes per 1000 CL days at baseline to 2.02 episodes per 1000 CL days (P < 0.01) during the intervention period., Lessons Learned: Adiós Bacteriemias was effective in reducing the incidence of CLABSI and improving the adherence to good practices for CL insertion and maintenance processes in participating ICUs in Latin America., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The number of centenarians is increasing with the aging of the Spanish population. This age group might present different clinical features from younger groups. This study was carried out to determine the impact hospital admission on centenarians with an acute disease., Materials and Methods: A retrospective observational study was conducted that included patients ≥100 years-old admitted from 1995 to 2016 to a third level university hospital and attended by the Geriatrics department in the acute ward, the Orthogeriatric ward, and by request. An analysis was made using the clinical-administrative databases containing information about the demographics, clinical, functional and cognitive features, length of hospital length, as well as discharge destination., Results: The study included 165 patients with a mean age of 101.6 ± 1.7 (range 100-109) years, of whom 140 (85%) were female. The mean hospital stay was 10.3 ± 7.4 days. Respiratory infections (41%) were the most common cause of admission to the Acute Geriatric Unit (AGU). The overall in-hospital mortality was 16%, but mortality in AGU reached up to 31%. There was an increase on moderate-severe functional disability (51% to 96%), and on the inability to walk independently (52% to 99%) from baseline to admission. There was a reduction in people living in their own home from 71% prior to admission to 29% at hospital discharge., Conclusions: Centenarians who required hospital admission showed a high rate of mortality, a significant deterioration in their functional capacity, and a decrease in their chances of going back to their own home at discharge., (Copyright © 2019 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Turbulence plays a major role in shaping marine community structure as it affects organism dispersal and guides fundamental ecological interactions. Below oceanographic mesoscale dynamics, turbulence also impinges on subtle physical-biological coupling at the single cell level, setting a sea of chemical gradients and determining microbial interactions with profound effects on scales much larger than the organisms themselves. It has been only recently that we have started to disentangle details of this coupling for swimming microorganisms. However, for non-motile species, which comprise some of the most abundant phytoplankton groups on Earth, a similar level of mechanistic understanding is still missing. Here, we explore by means of extensive numerical simulations the interplay between buoyancy regulation in non-motile phytoplankton and cellular responses to turbulent mechanical cues. Using a minimal mechano-response model, we show how such a mechanism would contribute to spatial heterogeneity and affect vertical fluxes and trigger community segregation.

Microorganismal motility is often characterized by complex responses to environmental physico-chemical stimuli. Although the biological basis of these responses is often not well understood, their exploitation already promises novel avenues to directly control the motion of living active matter at both the individual and collective level. Here we leverage the phototactic ability of the model microalga Chlamydomonas reinhardtii to precisely control the timing and position of localized cell photoaccumulation, leading to the controlled development of isolated bioconvective plumes. This novel form of photobioconvection allows a precise, fast, and reconfigurable control of the spatiotemporal dynamics of the instability and the ensuing global recirculation, which can be activated and stopped in real time. A simple continuum model accounts for the phototactic response of the suspension and demonstrates how the spatiotemporal dynamics of the illumination field can be used as a simple external switch to produce efficient bio mixing.

Screen-printed carbon nanofiber electrodes (SPCNFEs) represent an alternative with great acceptance due to their results, as well as their low impact on the environment. In order to improve their performance, in the present work they were modified with silver nanoparticles (Ag-NPs) and electrochemically characterized by using anodic stripping voltammetry. From the Ag-NP synthesis, silver seeds (Ag-NS) and silver nanoprisms (Ag-NPr) were obtained. The Ag-NP formation was confirmed by micrographs, where Ag-NPs with diameters of 12.20 ± 0.04 nm for Ag-NS and 20.40 ± 0.09 nm for Ag-NPr were observed. The electrodes were modified by using three different deposition methods-drop-casting, spin-coating, and in situ approaches-that offer different nanoparticle distribution and electrode modification times. It was observed that the last methodology showed a low amount of Ag-NS deposited on the electrode surface and deep alteration of this surface. Those facts suggest that the in situ synthesis methodology was not appropriate for the determination of heavy metals, and it was discarded. The incorporation of the nanoparticles by spin-coating and drop-casting strategies showed different spatial distribution on the electrode surface, as proved by scanning electron microscopy. The electrodes modified by these strategies were evaluated for the cadmium(II) and lead(II) detection using differential pulse anodic stripping voltammetry, obtaining detection limit values of 2.1 and 2.8 µg·L -1 , respectively. The overall results showed that the incorporation route does not directly change the electrocatalytic effect of the nanoparticles, but the shape of these nanoparticles (spherical for seeds and triangular for prisms) has preferential electrocatalytic enhancement over Cd(II) or Pb(II).

Finding a partner in an inherently unsteady 3-dimensional system, such as the planktonic marine environment, is a difficult task for nonswimming organisms with poor control over their orientation. We experimentally investigate the process of cell pairing in pennate marine diatoms and present field evidence of its occurrence in the ocean. We describe the mechanism as a 3-step process in which pennate diatoms ( i ) vertically reorient while sinking from surface turbulent waters to a more stable environment (i.e., under the seasonal pycnocline), ( ii ) segregate from incompatible partners (e.g., dead or different sized cells), and ( iii ) pair with other partners as a result of the hydrodynamic instabilities generated by collective cell sinking. This is, eminently, a cell abundance-dependent process, therefore being more effective when population sinking is synchronized. We suggest that this selective process, enabling matching of size-compatible healthy partners, could be fundamental in understanding sexual reproduction in pennate diatoms., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

A 496 L pilot scale anaerobic submerged membrane bioreactor (AnSMBR) for the treatment of municipal wastewater was evaluated during a year of stable operation at ambient (28-10 °C) temperature, and inoculated with mesophilic inoculum. The temperature was the main parameter affecting the process performance. The chemical oxygen demand (COD) of the effluent was around 150 mg O 2 /L in the summer period, operating with a volumetric loading rate (VLR) of 5 kg COD/m 3 d and hydraulic retention time (HRT) of 8-10 h, with a specific methane production between 0.09 and 0.14 Nm 3 /kg COD removed . However, during the winter season, an important increase of effluent COD was observed, and therefore the VLR was decreased to values around 1 kg COD/m 3 d in order to recover the quality of the effluent. Biogas production was negligible in this period. The effluent complies with the parameters stipulated by Spanish law regarding the use of treated wastewater for agricultural irrigation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Electrochemistry is a highly versatile part of chemical research which is involved in many of the processes in the field of micromotion. Its input has been crucial from the synthesis of microstructures to the explanation of phoretic mechanisms. However, using electrochemical effects to propel artificial micromotors is still to be achieved. Here, we show that the forces generated by electrochemical reactions can not only create active motion, but they are also strong enough to overcome the adhesion to the substrate, caused by the increased ionic strength of the solutions containing the ions of more noble metals themselves. The galvanic replacement of copper by platinum ions is a spontaneous process, which not only provides a sufficiently strong electromotive force to propel the Janus structures but also results in asymmetric Pt-hatted structures, which can be further used as catalytic micromotors.

Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia ), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with N G -nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N -ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.

The chemical synthesis of silver nanoparticles (Ag-NPs) by using an environmentally friendly methodology for their preparation is presented. Thus, considering that plants possess components that can act as reducing agents and stabilizers in nanoparticles' production, the synthesis of Ag-NPs by using an extract aqueous solution of grape stalk waste as a reducing and capping agent is studied. First, the total polyphenols and reducing sugars contained in the produced extracts at different conditions are characterized. After that, Ag-NPs are synthesized regarding the interaction of Ag ions (from silver nitrate) and the grape stalk extract. The effect of temperature, contact time, extract/metal solution volume ratio and pH solution in the synthesis of metal nanoparticles are also studied. Different sets of nanoparticle samples are characterized by means of Electron Microscopy coupled with Energy Dispersive X-Ray for qualitative chemical identification. Ag-NPs with an average diameter of 27.7 ± 0.6 nm are selected to proof their suitability for sensing purposes. Finally, screen-printed electrodes modified with Ag-NPs are tested for the simultaneous stripping voltammetric determination of Pb(II) and Cd(II). Results indicate good reproducibility, sensitivity and limits of detection around 2.7 µg L -1 for both metal ions.