Anthelmintic activity and chemical profile of native plant extracts from the Yucatan Peninsula against Toxocara canis.

Toxocara canis can produce the "larva migrans" syndrome in humans, and in puppies, it can cause severe digestive disorders. The most used treatments are based on anthelmintics, although there are reports of anthelmintic (AH) resistance. The Yucatan Peninsula has a great variety of plant species whose AH properties are still unknown. The objective of this study was to evaluate the in vitro AH activity of ethanolic (EE), methanolic (ME) and aqueous (AE) extracts from the leaves of five native plant species of the Yucatan Peninsula on T. canis eggs of dogs from Merida, Yucatan. As part of a screening, the EE of the plants Alseis yucatanensis, Calea jamaicensis, Cameraria latifolia, Macrocepis diademata, and Parathesis cubana were evaluated at doses of 2400 and 3600 µg/ml. The EE and AE of A. yucatanensis and M. diademata presented high percentages (≥ 91.3%) of inhibition of the larval development of T. canis after six days of exposure. The lowest LC50 and LC99 was presented by the ME from A. yucatanensis (255.5 and 629.06 µg/ml, respectively) and the ME from M. diademata (222.4 and 636.5 µg/ml, respectively), and the AE from A. yucatanenesis (LC50 of 535.9 µg/ml). Chemical profiling of the most potent AH extract (Alseis yucatanensis) was carried out by LC-UV-HRMS. Data from the ME and AE from this plant indicated the presence of the known glucosylngoumiensine, kaempferol 3,7-diglucosyde, uvaol, linoleic acid and linolenic acid together with unknown alkaloids. The EE, ME and AE from leaves of M. diademata and A. yucatanensis could be developed as natural alternatives to control T. canis.

Modelos experimentales murinos en la esclerosis lateral amiotrófica. Puesta al día / Murine experimental models of amyotrophic lateral sclerosis: An update

Introducción: La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa, progresiva y de etiología desconocida caracterizada por la degeneración de motoneuronas superiores e inferiores. Aproximadamente el 90% de los casos de ELA son esporádicos, mientras que el 10% restante se consideran familiares. Independientemente de si son familiares o esporádicas, los pacientes desarrollan una debilidad progresiva, atrofia muscular con espasticidad y contracturas. Por lo general, la esperanza de vida en los pacientes de ELA es de 2 a 5 años. Desarrollo: Los modelos in vivo han ayudado a explicar la etiología y la patogénesis, así como los mecanismos de la ELA. Sin embargo, estos mecanismos no están del todo esclarecidos aún, por lo que los modelos experimentales son fundamentales para continuar con el estudio de los mismos, así como para la búsqueda de posibles dianas terapéuticas. A pesar de que el 90% de los casos son esporádicos, la mayoría de los modelos utilizados hasta la actualidad para estudiar la patogénesis están basados en las mutaciones genéticas asociadas a la enfermedad familiar, lo que provoca que la patogénesis de la ELA esporádica no sea aún conocida. Por tanto, sería fundamental el estudio de la enfermedad en modelos basados en la enfermedad esporádica. Conclusión: En el presente artículo se han revisado los principales modelos experimentales, tanto genéticos como esporádicos, utilizados en el estudio de esta enfermedad, enfocándonos en los que se han desarrollado utilizando el roedor como plataforma experimental.(AU)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial or sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2–5 years after diagnosis. Development: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form. Conclusion: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.(AU)

Exploring dynamics of plant-herbivore interactions: bifurcation analysis and chaos control with Holling type-II functional response.

In this study, we examine the plant-herbivore discrete model of apple twig borer and grape vine interaction, with a particular emphasis on the extended weak-predator response to Holling type-II response. We explore the dynamical and qualitative analysis of this model and investigate the conditions for stability and bifurcation. Our study demonstrates the presence of the Neimark-Sacker bifurcation at the interior equilibrium and the transcritical bifurcation at the trivial equilibrium, both of which have biological feasibility. To avoid unpredictable outcomes due to bifurcation, we employ chaos control methods. Furthermore, to support our theoretical and mathematical findings, we develop numerical simulation techniques with examples. In summary, our research enhances the comprehension of the dynamics pertaining to interactions between plants and herbivores in the context of discrete-time population models.

Transcranial static magnetic stimulation reduces seizures in a mouse model of Dravet syndrome.

Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.

First report of acaricidal efficacy from plumbagin on larvae of Rhipicephalus microplus and Rhipicephalus sanguineus resistant to conventional acaricides.

The problem of resistance to acaricides in ticks such as Rhipicephalus microplus and R. sanguineus has motivated the search for control alternatives, such as the use of extracts and secondary metabolites from plants. Plumbagin is a natural product present in plants such as Plumbago zeylanica L., Diospyros kaki, and D. anisandra, of which acaricidal activity has been reported. Therefore, the objective of this study was to evaluate in vitro the acaricidal efficacy of plumbagin on larvae of R. microplus and R. sanguineus resistant to conventional acaricides. Larvae from engorged female ticks, collected from naturally infested dairy cattle and domiciled dogs, in Yucatan, Mexico, were used. The larval packet test and the larval immersion test were performed to detect acaricide susceptibility. Both tick populations were detected as resistant to cypermethrin and amitraz. Then, the modified larval immersion test was used and plumbagin was evaluated at concentrations of 1%, 0.5%, 0.25%, and 0.125% (%w/v), obtaining a mortality of 100% in the four concentrations for both tick species. Subsequently, lower doses of plumbagin were evaluated at concentrations of 0.0625%, 0.03125%, 0.015625% and 0.0078125%, obtaining mortalities of 100 to 36.26% for R. microplus and 100%-5.33% for R. sanguineus. Using Probit analysis, lethal concentrations at 50% (LC50), 99% (LC99) and confidence intervals at 95% (CI95%) were calculated. R. microplus showed a LC50 of 0.011% (CI95%: 0.010-0.011) and LC99 of 0.019% (CI95%: 0.018-0.022). R. sanguineus presented a LC50 of 0.017% (CI95%: 0.015-0.018) and CL99 of 0.031% (CI95%: 0.027-0.036). It was concluded that plumbagin has high acaricidal efficacy against larvae of R. microplus and R. sanguineus resistant to amitraz and cypermethrin. R. microplus larvae were significantly more susceptible to LC50 and LC99 compared to R. sanguineus. This is the first report on the acaricidal efficacy of plumbagin on larvae of R. microplus and R. sanguineus resistant to conventional acaricides.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

Recommendations for the prevention of healthcare-associated infections in nursing homes.

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similarities with a nosocomium as they are places where many patients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person responsible for implementing these projects. The document includes measures to be implemented and ways of quantifying the reality of different problems and of monitoring the impact of the measures established.

Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.

Murine experimental models of amyotrophic lateral sclerosis: an update.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis. DEVELOPMENT: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form. CONCLUSIONS: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.

La viruela del mono y el embarazo: una enfermedad olvidada y su impacto en la salud perinatal / Mpox and pregnancy: A neglected disease and its impact on perinatal health

Las infecciones virales durante el embarazo han sido una de las principales causas asociadas a problemas perinatales de gran importancia como lo son daños congénitos, síndromes neurológicos fetales, abortos y desenlaces adversos de la gestación. La infección por el virus de viruela del mono, causada por un Orthopoxvirus emparentado con el virus de la viruela humana, ha sido declarada por la Organización Mundial de la Salud en julio de 2022 una emergencia de salud global ante el gran número de casos surgidos fuera del área endémica habitual en África. Existe poca información sobre el impacto de la infección por el virus de la viruela del mono durante el embarazo, aunque las escasas evidencias disponibles muestran una alta tasa de daño fetal. En esta revisión se aborda el problema de la infección por el virus de la viruela del mono en mujeres embarazadas, proporcionando indicaciones para su prevención, su diagnóstico y su tratamiento (AU)

Viral infections during pregnancy have been one of the leading causes associated with significant perinatal problems, such as congenital defects, fetal neurological syndromes, stillbirths, and adverse pregnancy outcomes. The mpox virus infection, caused by an Orthopoxvirus related to the human smallpox virus, was declared a global health emergency by the World Health Organization in July 2022 due to the large number of cases emerging outside the usual endemic area in Africa. There is little information on the impact of mpox virus infection during pregnancy, although the limited evidence available shows a high rate of fetal harm. This review addresses the problem of mpox virus infection in pregnant women and provides indications for its prevention, diagnosis, and treatment (AU)

Air pollution relevance analysis in the bay of Algeciras (Spain).

The aim of this work is to accomplish an in-depth analysis of the air pollution in the two main cities of the Bay of Algeciras (Spain). A large database of air pollutant concentrations and weather measurements were collected using a monitoring network installed throughout the region from the period of 2010-2015. The concentration parameters contain nitrogen dioxide (NO2), sulphur dioxide (SO2) and particulate matter (PM10). The analysis was developed in two monitoring stations (Algeciras and La Línea). The higher average concentration values were obtained in Algeciras for NO2 (28.850 µg/m3) and SO2 (11.966 µg/m3), and in La Línea for PM10 (30.745 µg/m3). The analysis shows patterns that coincide with human activity. One of the goals of this work is to develop a useful virtual sensor capable of achieving a more robust monitoring network, which can be used, for instance, in the case of missing data. By means of trends analysis, groups of equivalent stations were determined, implying that the values of one station could be substituted for those in the equivalent station in case of failure (e.g., SO2 weekly trends in Algeciras and Los Barrios show equivalence). On the other hand, a calculation of relative risks was developed showing that relative humidity, wind speed and wind direction produce an increase in the risk of higher pollutant concentrations. Besides, obtained results showed that wind speed and wind direction are the most important variables in the distribution of particles. The results obtained may allow administrations or citizens to support decisions.

[Mpox and pregnancy: A neglected disease and its impact on perinatal health]. / La viruela del mono y el embarazo: una enfermedad olvidada y su impacto en la salud perinatal.

Viral infections during pregnancy have been one of the leading causes associated with significant perinatal problems, such as congenital defects, fetal neurological syndromes, stillbirths, and adverse pregnancy outcomes. The mpox virus infection, caused by an Orthopoxvirus related to the human smallpox virus, was declared a global health emergency by the World Health Organization in July 2022 due to the large number of cases emerging outside the usual endemic area in Africa. There is little information on the impact of mpox virus infection during pregnancy, although the limited evidence available shows a high rate of fetal harm. This review addresses the problem of mpox virus infection in pregnant women and provides indications for its prevention, diagnosis, and treatment.

Mpox and pregnancy: A neglected disease and its impact on perinatal health.

Viral infections during pregnancy have been one of the leading causes associated with significant perinatal problems, such as congenital defects, fetal neurological syndromes, stillbirths, and adverse pregnancy outcomes. The mpox virus infection, caused by an Orthopoxvirus related to the human smallpox virus, was declared a global health emergency by the World Health Organization in July 2022 due to the large number of cases emerging outside the usual endemic area in Africa. There is little information on the impact of mpox virus infection during pregnancy, although the limited evidence available shows a high rate of fetal harm. This review addresses the problem of mpox virus infection in pregnant women and provides indications for its prevention, diagnosis, and treatment.

Análisis del riesgo de ahogamiento asociado al entorno acuático y competencia natatoria / Analysis of the Drowning Risk Associated with Aquatic Environment and Swimming Ability

Un alto nivel de natación puede ser un factor protector ante el ahogamiento, sin embargo, esta relación todavía no ha sido empíricamente demostrada, en base al nivel de habilidad y entorno acuático. Este estudio diseñó una matriz de riesgo de ahogamiento en base al análisis probabilístico de un cuestionario respondido por 3.181 participantes. Se analizó la ocurrencia de Estrés/Distrés acuático (EDA) en base a 5 niveles de competencia y tres entornos acuáticos: a) Piscina sin olas ni corrientes, b) Lagos, embalses, ríos y playas sin olas ni corrientes, c) Ríos, playas o piscinas con olas y/o corrientes. Los resultados se expresaron en Odds Ratio (OR). El riesgo de EDA superó el OR de 25 en el entorno más peligroso y se incrementó para todos los escenarios conforme la competencia acuática era peor. Tres de cada cuatro nadadores han sufrido EDA y este evento pudo ser un incentivo para mejorar sus competencias acuáticas. (AU)

A high level of swimming can be a protective factor against drowning, however, this relationship has not yet been empirically demonstrated, based on water competence level and aquatic environment. This study designed a drowning risk matrix based on the probabilistic analysis of a questionnaire answered by 3,181 participants. The occurrence of Aquatic Stress/Distress (EDA) was analysed based on 5 skill levels and three aquatic scenarios: a) Pool without waves or currents, b) Lakes, reservoirs, rivers and beaches without waves or currents, c) Rivers, beaches or pools with waves and/or currents. The results were expressed in Odds Ratio (OR). EDA risk exceeded OR of 25 in the most dangerous environment and increased for all scenarios as aquatic competency worsened. Three out of four swimmers have suffered from EDA and this event could have been an incentive to improve their water competence. (AU)

Structured ternary fluids as nanocrystal incubators for enhanced crystallization control.

In crystallization from solution, a ubiquitous process in both industry and the natural world, nucleation is usually the rate-determining step, followed by faster crystal growth. Consequently, crystals typically exist in the nm-size range for such limited times that their investigation and manipulation is hindered. Here, we show that, owing to a degree of restricted diffusion, crystallization in structured ternary fluids (STFs) can proceed via higher nucleation rate and slower crystal growth pathways. This enables STFs to act as nanocrystal incubators, with the nanocrystals existing for extended times. We demonstrate that this generates enhanced crystallization control, with the three ambient pressure polymorphs of glycine, the α-, γ- and ß-forms, all crystallizing from the octanol/ethanol/water STF, despite the well-known difficulty in crystallizing the slow growing γ-form and the instability of the ß-form. The ability of STFs to produce notoriously hard to crystallize polymorphs should make them a versatile tool, ideal for polymorph discovery. This may enable a step change in the current, scatter-gun approach to polymorph screening. Furthermore, we show that aliquots of the nanocrystal-containing fluids can successfully seed metastable solutions. Hence, STFs may ultimately help provide a generic methodology for producing crystals and seed suspensions of any desired polymorph to supersede current targeted crystallization and seeding strategies.

Electrically stimulated droplet injector for reduced sample consumption in serial crystallography.

With advances in X-ray free-electron lasers (XFELs), serial femtosecond crystallography (SFX) has enabled the static and dynamic structure determination for challenging proteins such as membrane protein complexes. In SFX with XFELs, the crystals are typically destroyed after interacting with a single XFEL pulse. Therefore, thousands of new crystals must be sequentially introduced into the X-ray beam to collect full data sets. Because of the serial nature of any SFX experiment, up to 99% of the sample delivered to the X-ray beam during its "off-time" between X-ray pulses is wasted due to the intrinsic pulsed nature of all current XFELs. To solve this major problem of large and often limiting sample consumption, we report on improvements of a revolutionary sample-saving method that is compatible with all current XFELs. We previously reported 3D-printed injection devices coupled with gas dynamic virtual nozzles (GDVNs) capable of generating samples containing droplets segmented by an immiscible oil phase for jetting crystal-laden droplets into the path of an XFEL. Here, we have further improved the device design by including metal electrodes inducing electrowetting effects for improved control over droplet generation frequency to stimulate the droplet release to matching the XFEL repetition rate by employing an electrical feedback mechanism. We report the improvements in this electrically triggered segmented flow approach for sample conservation in comparison with a continuous GDVN injection using the microcrystals of lysozyme and 3-deoxy-D-manno-octulosonate 8-phosphate synthase and report the segmented flow approach for sample injection applied at the Macromolecular Femtosecond Crystallography instrument at the Linear Coherent Light Source for the first time.

Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.