Observer-based control for plasma glucose regulation in type 1 diabetes mellitus patients with unknown input delay.

This article introduces an observer-based control strategy tailored for regulating plasma glucose in type 1 diabetes mellitus patients, addressing challenges like unknown time-varying delays and meal disturbances. This control strategy is based on an extended Bergman minimal model, a nonlinear glucose-insulin model to encompass unknown inputs, such as unplanned meals, exercise disturbances, or delays. The primary contribution lies in the design of an observer-based state feedback control in the presence of unknown long delays, which seeks to support and enhance the performance of the traditional artificial pancreas by considering realistic scenarios. The observer and control gains for the observer-based control are computed through linear matrix inequalities formulated from Lyapunov conditions that guarantee closed-loop stability. This design deploys a soft and gentle dynamic response, similar to a natural pancreas, despite meal disturbances and input delays. Numerical tests demonstrate the scheme's effectiveness in glycemic level regulation and hypoglycemic episode avoidance.

The leachate from the Urban Solid Waste Transfer Station produces neurotoxicity in Wistar rats.

Leachate from municipal solid waste is a mixture of xenobiotics capable of contaminating bodies of water and causing damage to the health of living beings that inhabit or consume contaminated water. A previous study revealed the presence of heavy metals in Urban Solid Waste Transfer Station (USWTS) leachate above the permissible national and international limits. In the present study, we demonstrate that subchronic oral administration (5 and 25 % v/v) of leachate to male Wistar rats caused changes in the immunoreactivity of the glial markers: GFAP and Iba-1, accompanied by an increase in the expression of caspase-3, and a decrease in the expression of the NeuN protein. Results indicate that the heavy metals present in the leachate induced neuronal loss in the prefrontal cortex, suggesting that these contaminants can cause neurological problems in mammals that consume surface water with xenobiotics, since the leachate could contaminate water bodies and underground water.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.

Antibacterial and Antibiofilm Activity of Chemically and Biologically Synthesized Silver Nanoparticles.

Bacterial biofilms are a significant problem in the food industry, as they are difficult to eradicate and represent a threat to consumer health. Currently, nanoparticles as an alternative to traditional chemical disinfectants have garnered much attention due to their broad-spectrum antibacterial activity and low toxicity. In this study, silver nanoparticles (AgNPs) were synthesized by a biological method using a Jacaranda mimosifolia flower aqueous extract and by a chemical method, and the factors affecting both syntheses were optimized. The nanoparticles were characterized by Ultraviolet-visible (UV-Vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), Dynamic light scattering (DLS), X-ray diffraction (XRD), and Transmission electron microscopy (TEM) with a spherical and uniform shape. The antibacterial and antibiofilm formation activity was carried out on bacterial species of Pseudomonas aeruginosa and Staphylococcus aureus with the capacity to form biofilm. The minimum inhibitory concentration was 117.5 µg/mL for the chemical and 5.3 µg/mL for the biological nanoparticles. Both types of nanoparticles showed antibiofilm activity in the qualitative Congo red test and in the quantitative microplate test. Antibiofilm activity tests on fresh lettuce showed that biological nanoparticles decreased the population of S. aureus and P. aeruginosa by 0.63 and 2.38 logarithms, respectively, while chemical nanoparticles had little microbial reduction. In conclusion, the biologically synthesized nanoparticles showed greater antibiofilm activity. Therefore, these results suggest their potential application in the formulation of sanitizing products for the food and healthcare industries.

Can fluconazole be used for inpatient re-treatment of coccidioidomycosis among patients with past fluconazole exposures?

BACKGROUND: Coccidioides spp. may cause significant disease requiring hospitalisation, but optimal antifungal therapy among inpatients following outpatient fluconazole exposures is unknown. OBJECTIVES: The objective of this study is to describe the effectiveness of fluconazole among patients hospitalised for coccidioidomycosis despite recent outpatient fluconazole treatment. PATIENTS/METHODS: Patients were admitted to an academic medical center in Phoenix, Arizona from 1 January 2013 through 31 December 2020 for coccidioidomycosis following at least 30 days of outpatient treatment and re-initiation of fluconazole upon admission. The primary outcome was the proportion of patients with an improved response per the change in the modified Mycosis Study Group (MSG) score (a composite of symptoms, serology and radiographic findings) and clinician impressions. RESULTS: Sixty-seven patients were included, with most (54%) admitted to the intensive care unit. Meningitis was the most common infectious presentation (55%), 17 patients (25%) had multiple infection sites, and 23 (34%) were culture-positive for Coccidioides. Upon admission, the median (IQR) MSG score was 11 (9-14), which dropped to 4 (1-7) at end of therapy or last follow-up. Overall, after initiation of fluconazole therapy at a median daily dose of 800 mg, 48 patients (72%) improved in overall status, 10 (15%) showed stable disease and 9 (13%) were unresponsive. Improved response rates were high across all infection sites, including meningitis (68%) and bone infection (71%). There was no significant difference in response rates between patients with and without reported outpatient fluconazole nonadherence. CONCLUSIONS: The majority of patients admitted to the hospital for coccidioidomycosis appeared responsive to fluconazole therapy despite past outpatient exposures.

Bilateral ligation of the anterior trunk of the internal iliac artery in uterine atony secondary to uterine inversion: case report.

Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. Uterine atony is the main cause, representing up to 90% of cases, and is a risk factor for uterine inversion. Morbidity and mortality occur in 41% of uterine inversion cases, including massive obstetric hemorrhage. Massive obstetric hemorrhage is a medical emergency that puts life and reproductive function at risk, and therefore, its treatment must be timely and immediate. If there is no favorable response with the initial measures, surgical intervention proceeds. When choosing the surgical procedure, priority should be given to the technique with the easiest access and which is the least invasive, the safest, and in which the surgeon has more experience. We present a case report with our technique of bilateral ligation of the anterior trunk of the hypogastric artery, after a uterine compression suture failed, with excellent results and preserved fertility in an adolescent patient. We describe the technique and the result. The response time of the uterus with normal tone was 5 minutes, and postligation bleeding was only 50 mL after the patient had bled 1200 mL without complications; thus, it is an adequate and cost-effective technique. The bilateral ligation of the anterior trunk of the hypogastric artery technique in the case of postpartum hemorrhage is an effective, safe, and fertility-preserving surgical procedure that constitutes an alternative to emergency obstetrical hysterectomy when other, less invasive methods have failed.

Dopamine D2 and Adenosine A2A Receptors Interaction on Ca2+ Current Modulation in a Rodent Model of Parkinsonism.

SUMMARY STATEMENT: A2A receptor required previous D2 receptor activation to modulate Ca2+ currents. Istradefylline decreases pramipexole modulation on Ca2+ currents. Istradefylline reduces A2A + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity.

Toxicological Evaluation of Silver Nanoparticles Synthesized with Peel Extract of Stenocereus queretaroensis.

Silver nanoparticles (AgNPs) synthesized with plants are widely used in different industries, such as the medical, industrial, and food industries; however, their hazards and risks remain unclear. Here, we aimed to evaluate the toxicological effects of AgNPs in both in vitro and in vivo models. Previously, we developed and characterized green synthesized AgNPs based on Stenocereus queretaroensis (S. queretaroensis). The present study evaluates the toxicity of these AgNPs through cytotoxicity and mutagenicity tests in vitro, as well as genotoxicity tests, including the evaluation of acute oral, dermal, and inhalation toxicity, along with dermal and ocular irritation, in vivo, according to guidelines of The Organization for Economic Co-operation and Development (OECD). We evaluated cell cytotoxicity in L929 cells, and the half-maximal inhibitory concentration was 134.76 µg/mL. AgNPs did not cause genotoxic or mutagenic effects. Furthermore, in vivo oral, dermal, and acute inhalation toxicity results did not show any adverse effects or mortality in the test animals, and after the dermal and ocular irritation assessments, the in vivo models did not exhibit irritation or corrosion. Therefore, the results show that these previously synthesized S. queretaroensis AgNPs do not represent a risk at the tested concentrations; however, little is known about the effects that AgNPs induce on physiological systems or the possible risk following long-term exposure.

Natural essential oil mix of sweet orange peel, cumin, and allspice elicits anti-inflammatory activity and pharmacological safety similar to non-steroidal anti-inflammatory drugs.

An inflammation response occurs when the body reacts to exogenous and endo enous noxious stimuli, and it helps the body respond to infection and repair tissues, adapt to stress, and remove dead or damaged cells. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs are traditionally used to treat inflammation; however, these drugs often cause negative side effects. For this reason, developing and establishing effective alternative medicines for treating many chronic diseases with underlying inflammation is critically dependent on the identification of new organic molecules and bioactive substances. Aromatic and volatile compounds found in essential oils isolated from Pimenta dioica (allspice), Cuminum cyminum (cumin), and Citrus sinensis (sweet orange) are a source of bioactive compounds. Allspice essential oil reduces ear inflammation more than 65% and the anti-inflammatory activity of allspice essential oil is enhanced when combined with sweet orange peel and cumin essential oils, resulting in the reduction of edema inflammation by more than 85%, similar to indomethacin. As an alternative to anti-inflammatory treatment, essential oil mix is pharmacologically safe as it is neither toxic nor mutagenic.

Cristalogénesis biológica y cristalografía en la elucidación de la estructura tridimensional de las proteínas. Revisión narrativa / Protein tridimensional structure by biological crystallogenesis and crystallography. Narrative review

La obtención de información estructural tridimensional de una proteína es de suma importancia en campos tan variados como la bioquímica funcional, las ciencias de materiales o biomédicas. Siendo actualmente la difracción de rayos X de monocristal el estándar de oro para la consecución de este objetivo, la obtención de dicho monocristal sigue siendo un cuello de botella desde el punto de vista práctico, y poco entendido desde el punto de vista teórico. En este artículo se revisa desde la perspectiva estructural de la proteína la forma en que los rayos X permiten obtener la información estructural y las condiciones fisicoquímicas que permiten la formación de un cristal adecuado para estos experimentos.

Obtaining three-dimensional structural information of a protein is of utmost importance in various fields such as functional biochemistry, materials science, or biomedical sciences. Even though single crystal X-ray diffraction is currently the gold standard for this purpose, growing said single crystal is still a bottleneck from a practical viewpoint, and not fully understood from a theoretical point of view. In this article, we review, from a protein structure perspective, the way X-rays provide structural information, and the physicochemical conditions that promote the formation of an adequate crystal for these experiments.

Avances en Psicología Social Libertaria para autogestión activa: QCA mejorada y reflexiones desde República Dominicana / Advances in Libertarian Socialist Social Psychology’s Self-management: enhanced QCA and reflections from the Dominican Republic

Profundizo en una observación participante en una comunidad libertaria que emerge como mi-noría activa en las metrópolis de República Dominicana, mediante veinte entrevistas en pro-fundidad a diez personas a principios y a finales del 2013. Reconstruyo un modelo teórico dis-tinguiendo entre el compromiso de autogestión activo del pasivo. En este adelanto, presento una explicación mejorada del resultado de interés (laautogestión activa), gracias a un diálogo entre teorías y evidencias, junto a una revisión metodológica mejorada. Para la explicación de la autogestión activa, opto por la conjugación de dos condiciones principales: 1) las multiplici-dades discursivas, el solapamiento de herramientas comunitarias del discurso autogestionario como optimizadores de la autogestión; y 2) las actitudes personales que facilitan asumir un rol protagónico en el compromiso autogestionario como sujeto. Distingo esta explicación cuando hay un compromiso autogestionario libertario más general en comparación con el compromiso específicamente anarquista. (AU)

Drawing from exploratory participant observation with libertarian socialist groups and indi-viduals emerging as active minorities in the metropolitan areas of the Dominican Republic, twenty in-depth interviews were conducted with ten participants in the beginning and the end of 2013. An advanced theoretical model was reconstructed, which distinguished itself between the persons as the commitment of active self-management, and the passive self-management commitment. This improvement is done thanks to a more profound dialogue between theories and evidence and an enhanced methodological framework. From the explanation of the active self-management we can see the combination of: 1) discursive multiplicities, the overlap of communitarian tools of discourse self-management of the cases studied as optimizers; and 2) personal attitudes that facilitate one taking a protagonist role in self-management commit-ment as a subject. These conditions are differentiated when explaining the most general lib-ertarian socialist self-management commitment separated from the specifically anarchist commitment. (AU)

Aportes científicos del Instituto de Medicina Tropical "Pedro Kouri" a la vigilancia de Aedes aegypti (Díptera: Culicidae) en Cuba, 1982-2020

RESUMEN Entre las enfermedades de mayor incidencia en el mundo transmitidas por los culícidos o mosquitos se encuentran las arbovirosis como dengue, chikungunya, zika y fiebre amarilla, las cuales el humano las adquiere a través de la picadura de Aedes aegypti (Linnaeus, 1762) y Aedes albopictus (Skuse, 1894). Los programas de vigilancia entomológica de Ae. aegypti en el mundo tienen en común determinar cambios en la distribución geográfica del mosquito, obtener medidas relativas de sus poblaciones a lo largo del tiempo, evaluar la cobertura y el impacto de las intervenciones antivectoriales, así como monitorear la susceptibilidad y la resistencia de sus poblaciones a los principales insecticidas usados en el control vectorial. En este trabajo se resume los principales resultados de las investigaciones desarrolladas por el departamento de control de vectores del Instituto de Medicina Tropical ¨Pedro Kouri¨ (IPK) como Laboratorio Nacional de Referencia (LNR) para contribuir al fortalecimiento de la vigilancia entomológica de Ae. aegypti desde 1981 hasta el 2020. Con este artículo se destaca el trabajo realizado al cumplirse en el 2021, 40 años del inicio de la llamada campaña de erradicación de Ae. aegypti implementada a raíz de la epidemia de dengue hemorrágico (en la nueva clasificación denominada dengue severo) registrada en Cuba en 1981.

ABSTRACT Arbovirus infections such as dengue, chikungunya, zika and yellow fever are among the mosquito-borne diseases with the highest incidence worldwide. These conditions are transmitted by the bite of Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) mosquitoes. Common goals of entomological surveillance programs for Ae. aegypti in the world are to determine changes in the geographic distribution of the mosquito, obtain data concerning their populations throughout time, evaluate the coverage and impact of antivector interventions, and monitor the susceptibility and resistance of mosquito populations to the main insecticides used for vector control. The paper summarizes the main results of studies conducted from 1981 to 2020 by the Vector Control Department at Pedro Kourí Tropical Medicine Institute (IPK) as a National Reference Laboratory (NRL), to contribute to the strengthening of entomological surveillance of Ae. aegypti. Recognition is also made of the work done for forty years as part of the so-called Ae. aegypti eradication campaign implemented in response to the dengue hemorrhagic fever epidemic (severe dengue in the new classification) occurring in Cuba in 1981.

Landfill Leachate from an Urban Solid Waste Storage System Produces Genotoxicity and Cytotoxicity in Pre-Adolescent and Young Adults Rats.

Landfill leachate is a complex mixture of organic and inorganic molecules, as well as environmental pollutants that can cause harm to ecosystems and living beings. The micronucleus test in peripheral blood erythrocytes was used to evaluate the genotoxic and cytotoxic effects of exposure to a landfill leachate from an outdoor solid waste storage system on Wistar strain rats at different developmental stages, pre-adolescents and young adults, and the heavy metal content of the leachate was determined by atomic absorption spectrometry. Contents of arsenic, cadmium, chromium, mercury, and lead in the landfill leachate were outside the allowable international standards, and the exposure to the landfill leachate caused genotoxic and cytotoxic effects on Wistar rats, where the pre-adolescent animals were more susceptible to the toxics contained in the landfill leachate than young adults. Heavy metals contained in landfill leachate, individually or synergically with other molecules can be responsible for clastogenic and cytotoxic effects that can be harmful to humans and ecosystems.