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A method for the synthesis of rafoxanide 6, a halogenated salicylanilide used as an efficient anthelmintic in sheep and cattle, is presented. Rafoxanide 6 was synthesized in only three steps from readily available 4-chlorophenol with 74% overall yield. The synthesis has two key stages: the first was salicylic acid iodination, adding iodine in the presence of hydrogen peroxide, which allowed obtaining a 95% yield. The second key stage was the reaction of 3,5-diiodosalicylic acid 5 with aminoether 4, where salicylic acid chloride was formed in situ with PCl3 achieving 82% yield. Chemical characterization of both intermediates and final product was achieved through physical and spectroscopic (IR, NMR and MS) techniques. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-023-02846-9.

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RESUMEN Introducción: La hipertensión arterial es la más común de las enfermedades que afectan la salud de los individuos en las poblaciones mundiales. Objetivo: Evaluar el cumplimiento del Programa de Prevención, Diagnóstico y Control de la Hipertensión Arterial en el municipio Santa Clara, en el año 2016. Métodos: Se realizó una investigación observacional, descriptiva, de corte transversal en sistemas y servicios de salud. Se definieron criterios y variables, escala de clasificación, descripción operacional con indicadores y estándar, en tres dimensiones. Resultados: La dimensión estructura fue evaluada de no satisfactorio solo en el 30,76 %. En las dimensiones proceso y resultado todos los indicadores examinados resultaron no satisfactorios. Conclusiones: El Programa de Prevención, Diagnóstico y Control de la Hipertensión Arterial en el municipio de Santa Clara fue evaluado de no satisfactorio.

ABSTRACT Introduction: arterial hypertension is the most common of the diseases affecting individuals' health in world populations. Objective: to evaluate compliance with the Prevention, Diagnosis and Control Program of Arterial Hypertension in Santa Clara municipality, in 2016. Methods: an observational, descriptive and cross-sectional study was carried out in health systems and services. Criteria and variables, rating scale, operational description with indicators and standards were defined in three dimensions. Results: the structure dimension was evaluated as unsatisfactory only in 30.76%. All indicators examined in the result and process dimensions were unsatisfactory. Conclusions: the Prevention, Diagnosis and Control Program of Arterial Hypertension in Santa Clara municipality was evaluated as unsatisfactory.

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Resumen Presentamos el caso de una paciente que tenía un tumor del páncreas -denominado glucagonoma- y cuyo diagnóstico se sospechó por las manifestaciones cutáneas, las cuales nos condujeron realizar una tomografía axial computarizada (TAC). En ella se halló una masa. La paciente se remitió a cirugía y presentó una buena evolución.

Abstract This is a case report of a patient with a pancreatic tumor, known as glucagonoma, whose diagnosis was suspected because of skin manifestations which led to performing a CT scan, finding the mass. She underwent surgery with satisfactory results.

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Phytophthora cinnamomi is a phytopathogen that causes extensive damage in different crops, and therefore, produces important economic losses all around the world. Chemical fungicides are a key factor for the control of this disease. However, ecological and environmental considerations, as well as the appearance of strains that are resistant to commercial fungicides, have prompted the quest for new antifungal agents which are of low ecological impact. In this work, a series of new 2-allylphenol derivatives was synthesized, and their structures were confirmed by FT-IR, NMR, and MS. Some of the synthesized compounds, more specifically nitro derivatives, exhibit strong growth inhibition of P. cinnamomi with EC50 as low as 10.0 µg/mL. This level of activity is similar to that exhibited by METALAXYL MZ 58 WP, a commonly-used commercial fungicide; therefore, these compounds might be of agricultural interest due to their potential use as fungicides against P. cinnamomi. The results indicate that this activity depends on the chemical structures of the 2-allylphenol derivatives, and that it is strongly enhanced in molecules where nitro and hydroxyl groups adopt a -para configuration. These effects are discussed in terms of the electronic distribution of the aromatic ring induced by substituent groups.

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Botrytis cinerea is a worldwide spread fungus that causes the grey mold disease, which is considered the most important factor in postharvest losses in fresh fruit crops. Consequently, the control of gray mold is a matter of current and relevant interest for agricultural industries. In this work, a series of phenylpropanoids derived from eugenol were synthesized and characterized. Their effects on the mycelial growth of a virulent and multi-resistant isolate of B. cinerea (PN2) have been evaluated and IC50 values for the most active compounds range between 31⁻95 ppm. The antifungal activity exhibited by these compounds is strongly related to their chemical structure, i.e., increasing activity has been obtained by isomerization of the double bond or introduction of a nitro group on the aromatic ring. Based on the relationship between the fungicide activities and chemical structure, a mechanism of action is proposed. Finally, the activity of these compounds is higher than that reported for the commercial fungicide BC-1000 that is currently employed to combat this disease. Thus, our results suggest that these compounds are potential candidates to be used in the design of new and effective control with inspired natural compounds of this pathogen.

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Introducción: en la Unidad de Cuidados Intensivos del Hospital General Docente Dr. Agostinho Neto no se ha esclarecido la influencia de las estaciones del año en el perfil de la morbilidad y mortalidad. Objetivo: determinar la influencia de la variabilidad de las estaciones del año en el perfil de morbilidad y mortalidad de la UCI del HospitalGeneral Docente Dr Agostinho Neto durante el año 2018. Método: se hizo un estudio retrospectivo del total de pacientes ingresados (n=549) y seleccionó una muestra aleatoria de 365 pacientes. Las variables estudiadas fueron: edad, sexo, motivo de ingreso, índice de gravedad, estancia en la unidad, necesidad de ventilación mecánica, estado al egreso. Todas se relacionaron con las estaciones del año. Resultados: el mayor número de pacientes ingresó durante el verano (31,8 por ciento). No hubo relación significativa entre la estación del año y la variable sexo (p < 0,05), pero sí con la edad, APACHE II, estancia en la unidad y necesidad de ventilación mecánica (p < 0,05). En primavera y verano la enfermedad más común fue la cerebrovascular, mientras que en otoño e invierno la más común fue la neumonía grave adquirida en la comunidad. Las variables estancia en la unidad, ingreso de pacientes por enfermedades de carácter clínico según tipo de paciente clínico y mortalidad se relacionaron significativamente con la estación del año (p < 0,05). Conclusiones: la variabilidad climática del contexto guantanamero influyó en el perfil de morbilidad de la unidad de cuidados intensivos y midió el pronóstico de los pacientes que ingresan con enfermedad crítica(AU)

Introduction: in the intensive care unit of the General Teaching Hospital Dr Agostinho Neto the influence of the seasons of the year on the profile of morbidity and mortality has not been clarified. Objective: to determine the influence of the variability of season of the year on the morbidity and mortality profile of the ICU of the General Teaching Hospital Dr Agostinho Neto during the year 2018. Method: a retrospective study was made of the total number of admitted patients (n = 549) and a random sample of 365 patients was selected. The variables studied were: age, sex, reason for admission, severity index, stay in the unit, need for mechanical ventilation, discharge status. All were related to the weather. Results: the largest number of patients admitted during the summer (31.8per cent). There was no significant relationship between the weather station and the sex variable (p <0.05), but with age, APACHE II, stay in the unit and need for mechanical ventilation (p <0.05). In spring and summer the most common disease was cerebrovascular, while in autumn and winter the most common was community-acquired severe pneumonia. Thevariables stay in the unit, patient entry for diseases of a clinical nature according to the type of clinical patient and mortality were significantly related to the weather station (p <0.05). Conclusions: the climatic variability of the Guantanamo context influenced the morbidity profile of the intensive care unit and measured the prognosis of patients admitted with critical illness(AU)

Introdução: na unidade de terapia intensiva do Hospital Universitário Dr Agostinho Neto a influência das estações do ano sobre o perfil de morbidade e mortalidade ainda não foi esclarecida. Objetivo: determinar a influência da variabilidade das estações do ano no perfil de morbimortalidade da UTI do Hospital Universitário de General Dr Agostinho Neto durante o ano de 2018. Método: estudo retrospectivo do número total de pacientes internados (n = 549) e uma amostra aleatória de 365 pacientes foi selecionada. As variáveis estudadas foram: idade, sexo, motivo da internação, índice de gravidade, permanência na unidade, necessidade de ventilação mecânica, estado de descarga. Todos estavam relacionados com a estação do ano. Resultados: o maior número de pacientes internados no verão (31,8 por cento). Não houve relação significativa entre a estação do ano e a variável sexo (p <0,05), mas com a idade, APACHE II, permanecer na unidade e necessidade de ventilação mecânica (p <0,05). Na primavera e no verão, a doença mais comum era a cerebrovascular, enquanto no outono e no inverno a mais comum era pneumonia grave adquirida na comunidade. As variáveis permaneceram na unidade, a entrada do paciente para doenças de natureza clínica de acordo com o tipo de paciente clínico e a mortalidade foram significativamente relacionadas com o clima (p <0,05). Conclusões: a variabilidade climática do contexto de Guantánamo influenciou o perfil de morbidade da unidade de terapia intensiva e mediu o prognóstico de pacientes internados com doença crítica(AU)

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RESUMEN Introducción: los meningiomas de la vaina del nervio óptico son tumores meningoteliales originados de células aracnoideas que producen disminución de la visión y proptosis con un compromiso ocular variable. Presentación del caso: se trata de una paciente de 65 años de edad con antecedentes de hipertensión arterial que ingresó por proptosis, disminución de la visión y quemosis conjuntival del ojo derecho, evidenciándose en el examen del fondo de ojo la presencia de disco óptico pequeño de bordes definidos de coloración normal, sin compromiso del grosor de la capa de fibras nerviosas de la retina con dilatación vascular moderada a predominio venoso sin evidencia de alteraciones maculares, hemorragias ni exudados. Los estudios campimétricos evidenciaron la presencia de escotoma altitudinal con toma del cuadrante temporal inferior y el estudio de los potenciales evocados visuales mostró caída de su amplitud. Mediante el estudio de resonancia magnética nuclear se observó la existencia de una imagen isointensa homogénea de bordes bien definidos, que no comprometía la estructura axonal del nervio óptico y que respeta la porción intracanalicular e intracraneal, confirmándose el diagnóstico de meningioma de las vainas del nervio óptico. Conclusiones: Se confirma el diagnóstico de meningioma de las vainas del nervio óptico del ojo derecho en una paciente con proptosis unilateral y quemosis conjuntival, lo que constituye una inusual forma de presentación con manifestaciones oftalmológicas.

ABSTRACT Introduction: meningiomas of the optic nerve sheath are meningothelial tumors originating from arachnoid cells that produce decrease of vision and proptosis with variable ocular involvement. Case report: a 65-year-old female patient with a history of hypertension who was admitted due to proptosis, decrease of vision and conjunctival chemosis of the right eye; fundus of the eye examination revealed the presence of a small optic disc of defined edges of normal coloration, without compromise of the thickness of the layer of nervous fibers of the retina with moderate vascular dilatation to venous predominance without evidence of macular alterations, hemorrhages or exudates. The campimetric studies showed the presence of altitudinal scotoma with lower temporal quadrant capture, and the study of the visual evoked potentials showed fall of its amplitude. Through the study of nuclear magnetic resonance (NMR, the existence of a homogeneous isointense image of well-defined edges was observed, which did not compromise the axonal structure of the optic nerve and which respects the intracanalicular and intracranial portion that confirmed the diagnosis of meningioma of the optic nerve sheaths. Conclusions: the diagnosis of meningioma of the optic nerve sheaths on the right eye was confirmed in a patient with unilateral proptosis and conjunctival chemosis, which constitutes an unusual presentation with ophthalmological manifestations.

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Background: The biological behaviour and clinical significance of mercury toxicity vary according to its chemical structure. Mercury differs in its degree of toxicity and in its effects on the nervous, digestive and immune systems as well as on organs such as the lungs, kidneys, skin, eyes and heart. Human exposure occurs mainly through inhalation of elemental mercury vapours during industrial and artisanal processes such as artisanal and small-scale gold mining. Case presentation: A 52-years-old female, housewife, with a body mass index of 25.3 kg/cm², without smoking or alcohol habits or any important clinical or chronic cardiovascular history, was admitted to the emergency room due to probable accidental poisoning by butane gas. Clinical manifestations with a headache, dizziness, cough, and dyspnoea of medium to small efforts. An initial physical exploration with Glasgow scored at 15, with arrhythmic heart sounds, pulmonary fields with bilateral subcrepitant rales and right basal predominance. Electrocardiographic findings were as follows: a cardiac frequency of 50 beats per minute and atrioventricular dissociation. Laboratory parameters were: white blood cells at 15.8 × 108/L; aspartate aminotransferase at 38 U/L; lactate dehydrogenase at 1288 U/L; creatine-kinase at 115 U/L; CK-MB fraction at 28 U/L; and other biochemical parameters were within the reference values. A radiographic evaluation showed flow cephalization, diffuse bilateral infiltrates with right basal predominance. In addition, the patient presented data of low secondary expenditure to third-degree atrioventricular (AV) block for which the placement of a transvenous pacemaker was decided, substantially improving the haemodynamic parameters. Subsequently, after a family interrogation, the diagnosis of mercury inhalation poisoning was established. An initial detection of mercury concentration (Hg(0)) was carried out, reporting 243.5 µg/L. In view of this new evidence, mercury chelation therapy with intravenous calcium disodium ethylenediamine tetraacetic acid (CaNa2·EDTA) was initiated. After 8-days of hospital stay, she presented a favourable evolution with both clinical and radiological improvements, so that the mechanical ventilation progressed to extubating. Subsequently, she was referred for cardiology because of her persistent 3rd-degree atrioventricular block, deciding to place a definitive bicameral pacemaker. The patient was discharged from the hospital 14 days after admission due to clinical improvements with mercury plasma levels at 5 µmol/L and a heart rhythm from the pacemaker. Conclusions: We show evidence that acute exposure to elemental mercury can affect the heart rhythm, including a complete atrioventricular blockage.

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The antifungal activity of polygodial, a secondary metabolite extracted from Canelo, on mycelial growth of different Botrytis cinerea isolates has been evaluated. The results show that polygodial affects growth of normal and resistant isolates of B. cinerea with EC50 values ranging between 117 and 175 ppm. In addition, polygodial markedly decreases the germination of B. cinerea, i.e., after six hours of incubation the percentage of germination decreases from 92% (control) to 25% and 5% in the presence of 20 ppm and 80 ppm of polygodial, respectively. Morphological studies indicate that conidia treated with polygodial are smaller, with irregular membrane border, and a lot of cell debris, as compared to conidia in the control. The existence of polygodial-induced membrane damage was confirmed by SYTOX® Green uptake assay. Gene expression studies confirm that the effect of polygodial on B. cinerea is mainly attributed to inhibition of germination and appears at early stages of B. cinerea development. On the other hand, drimenol, a drimane with chemical structure quite similar to polygodial, inhibits the mycelial growth efficiently. Thus, both compounds inhibit mycelial growth by different mechanisms. The different antifungal activities of these compounds are discussed in terms of the electronic density on the double bond.

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The aim of this study was to determine the antifungal activity of Drimenol (1) and its synthetic derivatives, nordrimenone (2), drimenyl acetate (3), and drimenyl-epoxy-acetate (4), and to establish a possible mechanism of action for drimenol. For that, the effect of each compound on mycelial growth of Botrytis cinerea was assessed. Our results showed that compounds 1, 2, 3 and 4 are able to affect Botrytis cinerea growth with EC50 values of 80, 92, 80 and 314ppm, respectively. These values suggest that the activity of these compounds is mainly determined by presence of the double bond between carbons 7 and 8 of the drimane ring. In addition, germination of B. cinerea in presence of 40 and 80ppm of drimenol is reduced almost to a half of the control value. Finally, in order to elucidate a possible mechanism by which drimenol is affecting B. cinerea, the determination of membrane integrity, reactive oxygen species production and gene expression studies of specific genes were performed.

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