Ultrasonic or Microwave Modified Continuous Flow Chemistry for the Synthesis of Tetrahydrocannabinol: Observing Effects of Various Solvents and Acids.

Synthesizing tetrahydrocannabinol is a lengthy process with minimal yields and little applicability on an industrial scale. To close the gap between bench chemistry and industry process chemistry, this paper introduces a small-scale flow chemistry method that utilizes a microwave or ultrasonic medium to produce major tetrahydrocannabinol isomers. This process produces excellent yields and minimal side products, which leads to more efficient large-scale production of the desired cannabinoids.

Psychoactive Isoxazoles, Muscimol, and Isoxazole Derivatives from the Amanita (Agaricomycetes) Species: Review of New Trends in Synthesis, Dosage, and Biological Properties.

Herbal products found in nature can serve as great systems of study for drug design. The Amanita muscaria mushroom is native to many parts of the Northern Hemisphere and has a very distinctive appearance with its red cap and white spotted warts. The mushroom comprises several pharmacologically active alkaloids, including muscazone, muscarine, ibotenic acid, and muscimol, the latter two compounds being potent GABA agonists. Muscimol has served as a backbone in the design of GABA agonists devoid of effects on the GABA-metabolizing enzyme, GABA transaminase, and GABA uptake systems. In this sense, several analogs of muscimol have been synthesized and studied including THIP, THPO, iso-THIP, iso-THAZ and 4-PIOL which all interact with the GABA receptors much differently. The growing pharmacological and toxicological interest based on many conflicting opinions on the use of the neuroprotective role of muscimol analogs against some neurodegenerative diseases, its potent role in the treatment of cerebral ischemia and other socially significant health conditions provided the basis for this review.

Saturated Cannabinoids: Update on Synthesis Strategies and Biological Studies of These Emerging Cannabinoid Analogs.

Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of various classical, hybrid, and non-classical saturated cannabinoids. A discussion of structure-activity relationships with the four different pharmacophores found in the cannabinoid scaffold is added to this review. According to laboratory studies in vitro, and in several animal species in vivo, HHC is reported to have broadly similar effects to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive substance in cannabis, as demonstrated both in vitro and in several animal species in vivo. However, the effects of HHC treatment have not been studied in humans, and thus a biological profile has not been established.

Sensitization to Aeroallergens in a Mexican Cohort with Allergic Conjunctivitis: A Cross-sectional Retrospective Study Conducted in Ángeles Puebla Hospital.

This study aims to evaluate the sensitization distribution of aeroallergens in patients with allergic conjunctivitis (AC) living in a temperate subhumid region and to describe the prevalence in a Mexican cohort. A total of 761 patient records were revisited, including the results of the skin prick test (SPT) for 45 aeroallergens. We found 292 patients with AC and a positive SPT in a 5-year period. The most frequent aeroallergens include dust mites (69.2% for Dermatophagoides pteronyssinus and 47.6% for Dermatophagoides farinae), trees (36% for cypress and 22.6% for ash), animals (33.9% for dogs and 26.7% for cats), and grasses (21.2% for Paspalum notalum and 19.9% for Poa pratensis). Among the studied population, a prevalence of 38.4% for the disease was calculated. House dust mites were responsible for most sensitizations found in the studied population. There is a high prevalence of AC in the selected cohort during the period studied.

Eptinezumab-jjmr, a humanized monoclonal specific to Calcitonin Gene Related Peptide, for the preventive treatment of migraine in adults.

Purpose of Review: Migraines are prevalent and cause significant morbidity, decline in quality of life and healthcare costs universally. Treatment options are varied, but efficacy is limited. This review centers on Eptinezumab-jjmr, a humanized monoclonal specific to CGRP for the prevention of migraines in adults. Herein presented are the science and mechanism of action, indication and clinical evidence for use. Recent Findings: Migraines are severe, recurrent headaches, which are either episodic or chronic in nature. The pain is severe, often accompanied by co-morbid symptoms, such as photophobia, phonophobia, nausea and emesis, and is limiting in nature. It is a prevalent disorder that causes significant, worldwide disability, morbidity, suffering, and costs.The pathophysiology of migraines is actively studied, though recent research points to an initiating event causing migraine generation, that is then propagated by other brain regions, a significant one being the trigeminocervical complex. This is driven by biochemical transmitters, chiefly CGRP. This discovery led to the development of CGRP-targeting drugs, including gepants (small molecular antagonists) and anti-CGRP antibodies, such as Eptinezumab-jjmr.Traditional therapy includes preventative and abortive treatment; however, adherence with preventative treatment has been historically poor, and certain types of abortive therapy carry risks and side effects that preclude them from a large patient population. Moreover, traditional therapy often falls short in migraine therapy. CGRP antagonist, including Eptinezumab, aims to cover the gaps in migraine therapy. We present here evidence to support the safe and effective use of Eptinezumab for the prevention of migraines. Summary: Migraines are a prevalent primary headache disorder causing significant morbidity worldwide. Traditional abortive and preventative treatments fall short for many patients. Eptinezumab is part of new generation of CGRP-targeting medications and has shown significant evidence to support its use for the prevention of migraines. Further research is required to properly compare eptinezumab with existing pharmacotherapy and update guidelines on the appropriate combinations of therapies that are not available and the correct patient selection for each.

Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review.

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible.

Rimegepant for the treatment of migraine.

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide relief in severe migraine, but are not universally effective and carry a significant side-effect profile with frequent redosing requirement. Prophylactic therapy may reduce the occurrence of acute migraine attacks in selected patients, but does not completely eliminate it. More recently, CGRP antagonism has been studied and shown to be effective in both abortion and prevention of migraine. Novel medications, targeting CGRP, divide into CGRP antibodies and receptor antagonists (gepants). Rimegepant, a second-generation gepant, has shown efficacy in several clinical trials in treating acute migraine. Ongoing trials are also evaluating its role in migraine prophylaxis, and results are promising. It is also generally safer for use than existing options, does not appear to increase the chance of developing chronic migraines, and carries a very tolerable side effects profile. It is a part of a growing arsenal in migraine treatment, and may present the silver bullet for treatment of this disease.

Review of Interventional Therapies for Refractory Pediatric Migraine.

This is a review of the latest and seminal evidence in pediatric migraine. It covers the etiology and pathophysiology known today, and then will review treatment options, efficacy and safety, quality of data and indications. Though migraine is usually regarded as an infliction in adults, it is not uncommon in the pediatric population and affects up to 8% of children. Children may experience migraine differently than adults, and present not only with headache but also frequent gastrointestinal symptoms. They are frequently shorter in duration than in adults. Traditional migraine treatment in adults is less effective in children. In this population, adjunct therapies - such as interventional techniques - should be considered when traditional treatment fails, including Botulinum Toxin A (BTA) injections, peripheral nerve and ganglion blocks. BTA injections are FDA approved for migraine prophylaxis in adults, but currently not in children; however, recent evidence shows efficacy and safety in pediatric migraine management. Nerve blocks stop nociceptive afferent fibers through injection of local anesthetics, and it may be associated with the local injection of corticosteroids. Although more common in adults, recent data suggests they are safe and effective in children and adolescents. Blocking the sphenopalatine ganglion can be achieved through nasal approach, and achieves a similar action by blocking the entire ganglion. Interventional techniques may provide a key component in the alleviation of this otherwise debilitating chronic migraine pain. Though most studies have been performed in adults, new studies provide encouraging results for treatment in children.

Characterization of Fungal Endophytes Isolated from the Metal Hyperaccumulator Plant Vachellia farnesiana Growing in Mine Tailings.

Heavy metal pollution has become an environmental and health problem worldwide. With the aim of finding novel strategies for metal bioremediation, endophytic fungi from the heavy metal hyperaccumulator plant Vachellia farnesiana were isolated and characterized. The plants were growing in mine tailings, rich in Zn, Pb, and Cu. Morphological and phylogenetic analyses indicated that the fungal strains belonged to Neocosmospora and Aspergillus genera. The Neocosmospora isolate belongs to the Fusarium solani species complex (FSSC) that groups phytopathogen species. However, in this case the plants from which it was isolated did not show any signs of disease. Both fungal strains were able to remove significant amounts of heavy metals from liquid cultures, either in a mixture of the three metals or each metal in a single culture. In response to lead exposure, the Neocosmospora sp. strain secreted specific novel phenolic compounds other than anthraquinones or naphtoquinones, which have been described in similar situations. The Aspergillus sp. dropped the pH in the medium. High-performance liquid chromatography determinations indicated that this strain secreted mainly glutamic acid in response to lead, a novel mechanism, which has not been reported elsewhere. Malic and succinic acids were also produced in response to lead exposure. Possibly, glutamic and succinic acids (synthesized in the Krebs cycle) can be used to cope with metal toxicity due to the plant providing photosynthates to the fungus. These fungi showed the potential to be used for bioremediation or restoration of metal-polluted environments.

Novel ALD Chemistry Enabled Low-Temperature Synthesis of Lithium Fluoride Coatings for Durable Lithium Anodes.

Lithium metal anodes can largely enhance the energy density of rechargeable batteries because of the high theoretical capacity and the high negative potential. However, the problem of lithium dendrite formation and low Coulombic efficiency (CE) during electrochemical cycling must be solved before lithium anodes can be widely deployed. Herein, a new atomic layer deposition (ALD) chemistry to realize the low-temperature synthesis of homogeneous and stoichiometric lithium fluoride (LiF) is reported, which then for the first time, as far as we know, is deposited directly onto lithium metal. The LiF preparation is performed at 150 °C yielding 0.8 Å/cycle. The LiF films are found to be crystalline, highly conformal, and stoichiometric with purity levels >99%. Nanoindentation measurements demonstrate the LiF achieving a shear modulus of 58 GPa, 7 times higher than the sufficient value to resist lithium dendrites. When used as the protective coating on lithium, it enables a stable Coulombic efficiency as high as 99.5% for over 170 cycles, about 4 times longer than that of bare lithium anodes. The remarkable battery performance is attributed to the nanosized LiF that serves two critical functions simultaneously: (1) the high dielectric value creates a uniform current distribution for excellent lithium stripping/plating and ultrahigh mechanical strength to suppress lithium dendrites; (2) the great stability and electrolyte isolation by the pure LiF on lithium prevents parasitic reactions for a much improved CE. This new ALD chemistry for conformal LiF not only offers a promising avenue to implement lithium metal anodes for high-capacity batteries but also paves the way for future studies to investigate failure and evolution mechanisms of solid electrolyte interphase (SEI) using our LiF on anodes such as graphite, silicon, and lithium.

[Neurological manifestations in atypical Kawasaki disease]. / Manifestaciones neurológicas en la enfermedad de Kawasaki atípica.

BACKGROUND: Kawasaki disease (KD) is a type of systemic vasculitis of unknown etiology. Atypical Kawasaki disease is defined as that where there are signs and symptoms not corresponding to the classical criteria for this nosological entity. Children with atypical Kawasaki disease may present with acute abdominal symptoms, meningeal irritation, pneumonia or renal failure. CLINICAL CASES: We describe 4 children with ages ranging from 2 to 12 years who had atypical Kawasaki disease, with neurological and gastrointestinal symptoms as part of the systemic presentation of the disease. Treatment consisted of immunoglobulin and corticosteroids with good evolution. CONCLUSIONS: KD is a systemic vasculitis that can involve many territories. Atypical manifestations can mislead the clinician and delay diagnosis. Pediatricians and sub-specialists should be aware of these neurological manifestations in order to provide adequate and opportune treatment.

Antecedentes: La enfermedad de Kawasaki es una vasculitis sistémica de etiología desconocida. La modalidad atípica se define como aquella en la cual hay signos y síntomas que no corresponden a los criterios clásicos de esta entidad nosológica. Los niños con enfermedad de Kawasaki atípica pueden presentar síntomas abdominales agudos, irritación meníngea, neumonía o falla renal. Casos clínicos: Describimos 4 niños con edades que oscilaron entre los 2 y 12 años que presentaron enfermedad de Kawasaki atípica, con síntomas neurológicos y gastroinstetinales como parte de la presentación sistémica de la enfermedad. El tratamiento se llevó a cabo con corticosteroides e inmunoglobulina, con los cuales los pacientes evolucionaron satisfactoriamente. Conclusiones: La enfermedad de Kawasaki es una vasculitis sistémica que puede involucrar numerosos aspectos. Las manifestaciones atípicas pueden confundir al clínico y retrasar el diagnóstico. Los pediatras y subespecialistas deben estar conscientes de estas manifestaciones neurológicas, con el fin de proporcionar tratamiento adecuado y oportuno.

Carbon-based tribofilms from lubricating oils.

Moving mechanical interfaces are commonly lubricated and separated by a combination of fluid films and solid 'tribofilms', which together ensure easy slippage and long wear life. The efficacy of the fluid film is governed by the viscosity of the base oil in the lubricant; the efficacy of the solid tribofilm, which is produced as a result of sliding contact between moving parts, relies upon the effectiveness of the lubricant's anti-wear additive (typically zinc dialkyldithiophosphate). Minimizing friction and wear continues to be a challenge, and recent efforts have focused on enhancing the anti-friction and anti-wear properties of lubricants by incorporating inorganic nanoparticles and ionic liquids. Here, we describe the in operando formation of carbon-based tribofilms via dissociative extraction from base-oil molecules on catalytically active, sliding nanometre-scale crystalline surfaces, enabling base oils to provide not only the fluid but also the solid tribofilm. We study nanocrystalline catalytic coatings composed of nitrides of either molybdenum or vanadium, containing either copper or nickel catalysts, respectively. Structurally, the resulting tribofilms are similar to diamond-like carbon. Ball-on-disk tests at contact pressures of 1.3 gigapascals reveal that these tribofilms nearly eliminate wear, and provide lower friction than tribofilms formed with zinc dialkyldithiophosphate. Reactive and ab initio molecular-dynamics simulations show that the catalytic action of the coatings facilitates dehydrogenation of linear olefins in the lubricating oil and random scission of their carbon-carbon backbones; the products recombine to nucleate and grow a compact, amorphous lubricating tribofilm.

Tribochemistry of Carbon Films in Oxygen and Humid Environments: Oxidative Wear and Galvanic Corrosion.

The effects of oxidation on wear of carbon/steel tribological interfaces were studied. When mechanical wear was small, the oxidation behavior of hydrogenated diamond-like carbon (H-DLC) and stainless steel (SS) sliding interface varied depending on the nature of the oxidizing environment. In dry air or oxygen, both H-DLC and SS wore readily. The wear debris of SS did not form iron oxide in dry air and oxygen. In humid nitrogen, however, the wear of H-DLC diminished with increasing humidity, and the SS surface showed mild wear and iron oxide debris accumulated around the sliding contact region. These results revealed that different tribochemical reactions occur in dry oxygen and humid environments. In the absence of water, oxygen oxidizes the H-DLC surface, making it susceptible to wear, creating debris, and inducing wear on both H-DLC and SS. In contrast, adsorbed water molecules at less than 40% RH act as a molecular lubricant of the oxidized DLC surface, while multiwater layers adsorbed at near-saturation act as electrolyte inducing electrochemical galvanic corrosion reactions on the SS surface. When hydrogen-free amorphous carbon (a-C) was used in tribo-tests, severe wear of the SS surface occurs, in addition to the tribochemical wear observed for H-DLC, due to the high hardness of the a-C film.

Evaluating trauma care capabilities in Mexico with the World Health Organization's Guidelines for Essential Trauma Care publication.

OBJECTIVE: To identify affordable, sustainable methods to strengthen trauma care capabilities in Mexico, using the standards in the Guidelines for Essential Trauma Care, a publication that was developed by the World Health Organization and the International Society of Surgery to provide recommendations on elements of trauma care that should be in place in the various levels of health facilities in all countries. METHODS: The Guidelines publication was used as a basis for needs assessments conducted in 2003 and 2004 in three Mexican states. The states were selected to represent the range of geographic and economic conditions in the country: Oaxaca (south, lower economic status), Puebla (center, middle economic status), and Nuevo León (north, higher economic status). The sixteen facilities that were assessed included rural clinics, small hospitals, and large hospitals. Site visits incorporated direct inspection of physical resources as well as interviews with key administrative and clinical staff. RESULTS: Human and physical resources for trauma care were adequate in the hospitals, especially the larger ones. The survey did identify some deficiencies, such as shortages of stiff suction tips, pulse oximetry equipment, and some trauma-related medications. All of the clinics had difficulties with basic supplies for resuscitation, even though some received substantial numbers of trauma patients. In all levels of facilities there was room for improvement in administrative functions to assure quality trauma care, including trauma registries, trauma-related quality improvement programs, and uniform in-service training. CONCLUSIONS: This study identified several low-cost ways to strengthen trauma care in Mexico. The study also highlighted the usefulness of the recommended norms in the Guidelines for Essential Trauma Care publication in providing a standardized template by which to assess trauma care capabilities in nations worldwide.

Evaluating trauma care capabilities in Mexico with the World Health Organization's Guidelines for Essential Trauma Care publication

OBJETIVO: Identificar formas asequibles y sustentables de reforzar los recursos para la atención de heridos en México aplicando las pautas contenidas en Guidelines for Essential Trauma Care [Pautas para el tratamiento básico de los heridos], publicación de la Organización Mundial de la Salud y de la Sociedad Quirúrgica Internacional que contiene recomendaciones sobre los componentes de la atención de heridos que deben poseer los servicios de salud de distintos niveles en todos los países. MÉTODOS: Las pautas publicadas (Guidelines) sirvieron de base para llevar a cabo evaluaciones de las necesidades en tres estados mexicanos en 2003 y en 2004. Los estados se escogieron con la idea de que estuviese representada la amplia variedad de condiciones geográficas y económicas del país: Oaxaca (en el sur y de estrato económico inferior), Puebla (en el centro y con un estrato económico mediano) y Nuevo León (en el norte y con un estrato económico más alto). Se evaluaron dieciséis centros entre los cuales había puestos de salud rurales, hospitales pequeños y hospitales grandes. Se hicieron visitas a todos los centros para llevar a cabo la inspección directa de los recursos físicos en cada uno y entrevistar a miembros clave del personal administrativo y clínico. RESULTADOS: Los recursos humanos y físicos destinados a la atención de heridos eran de calidad satisfactoria en los hospitales, especialmente los más grandes. La encuesta reveló algunas deficiencias, tales como una escasez de succionadores rígidos, oxímetros de pulso y algunos medicamentos usados para tratar heridos. En todos los puestos se observaron dificultades con los equipos básicos de reanimación, a pesar de que algunos recibían un número bastante alto de heridos. En los centros de todos los niveles había margen para mejorar las funciones administrativas a fin de conseguir una atención de calidad que incluyese el mantenimiento de registros de heridos, programas para mejorar la atención de estos pacientes y uniformidad en el adiestramiento del personal durante el desempeño de sus funciones. CONCLUSIONES: En este estudio se identificaron varias formas baratas de reforzar la atención de pacientes heridos en México. También se subrayó la utilidad de las pautas recomendadas en la obra Guidelines for Essential Trauma Care como modelo estandarizado para evaluar los recursos para el tratamiento de heridos que poseen los países en cualquier parte del mundo.

Neurocisticercosis parenquimatosa activa: reporte de un caso y revisión de la literatura / Active parenchymatous neurocysticercosis: report of a case and review of literature

Se presenta el caso de una paciente nicaragüense con neurocisticercosis parenquimatosa activa, cuya manifestación principal es la pérdida de la agudeza visual. En los estudios de imágenes, por medio de Tomografía Axial Computarizada y Resonancia Magnética Nuclear, se observan lesiones sugestivas de toxoplasmosis o de cisticercosis. El diagnóstico se confirma al efectuar la determinación de anticuerpos anticisticerco en líquido cefalorraquídeo por medio de un ELISA; otras pruebas de laboratorio, como el análisis citoquímico de líquido cefalorraquídeo, hemograma y bioquímica en sangre, dieron resultados dentro de límites normales. Se le administra albendazone (500 miligramos) dos veces por día por 30 días acompañado de antiinflamatorios y anticonvulsivos. La agudeza visual no mejoró posterior al tratamiento. Palabras clave: Cystercus cellulosae, neurocisticercosis, Taenia solium, abendazole, neuritis óptica