Investigating the (Poly)Radicaloid Nature of Real-World Organic Compounds with DFT-Based Methods

Recent advances in the synthesis of stable organic (open-shell) polyradicaloids have opened their application as active compounds for emerging technologies. These systems typically exhibit small energy differences between states with different spin multiplicities, which are intrinsically difficult to calculate by theoretical methods. We thus apply here some DFT-based variants (FT-DFT, SF-DFT, and SF-TDDFT) on a test set of large and real-world molecules, as test systems for which such energy differences are experimentally available, also comparing systematically with RAS-SF results to infer if shortcomings of previous DFT applications are corrected. Additionally, we explore the spin–spin contribution to the ZFS tensor, of high interest for EPR spectroscopy, and derive the spatial extent of the corresponding (photoexcited) triplet state.G.S. acknowledges the Erasmus+ program for a research internship. D.C. is thankful to projects PIBA19-0004 (Eusko Jaurlaritza) and CTQ2016-80955-P from the Spanish Government (MINECO/FEDER)

Prevalence of human cystic echinococcosis in the towns of Ñorquinco and Ramos Mexia in Rio Negro Province, Argentina, and direct risk factors for infection

Fil: Uchiumi, Leonardo. Ministerio de Salud de Rio Negro, Hospital Zatti,, Rio NegroFil: Mugica, Guillermo. Ministerio de Salud de Rio Negro, Salud Ambiental, Rio NegroFil: Araya, Daniel. Ministerio de Salud de Rio Negro, Ssluf Ambiental, Rio NegroFil: Salvitti, Juan. Ministerio de Salud de Rio Negro, Hospital Bariloche, Rio NegroFil: Sobrino, Mariano. Ministerio de Salud de Rio Negro, Hospital Bariloiche, Rio NegroFil: Moguilansky, Sergio. Universidad Nacional del Comahue, Catedra de Imagenes, Rio NegroFil: Solari, Santiago. Ministerio de Salud de Rio Negro, Hospital Valcheta, Rio NegroFil: Blanco, Patricia. Ministerio de Salud de Rio Negro, Salud Ambiental, Rio NedgroFil: Lamounier, Janette. Ministerio de Salud de Rio Negro, Hospital Ñorquinco, Rio NegroFil: Barrera, Federica. Ministerio de Salud de Rio Negro, Hospital Ramos Mexia, Rio NegroFil: Arezo, Marcos. Ministerio de Salud de Rio Negro, Salud Ambiental, Rio NegroFil: Seleiman, Marcos. Ministerio de Salud de Rio Negro, Salud Ambiental, Rio NegroFil: Yadon, Zaida. Academia Nacional de Medicina, Instituto investigaciones Epidemiologicas. Buenos AiresFil: Tamarozzi, Feamcesca. Universidad de La Sapienzia, Roma, ItaliaFil: Casulli, Adriano. Universidad de Las Sapienza, FRoma, ItaliaFil: Larrieu, Edmundo. Universidad Nacional de Rio Negro, Escuela de Veterinaria. Rio Negro. Argentina.Background: Cystic echinococcosis (CE) is a parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus (s.l.). This study investigated the prevalence and potential risk factors associated with human CE in the towns and rural areas of Ñorquinco and Ramos Mexia, Rio Negro province, Argentina. Methods: To detect abdominal CE cysts, we screened 892 volunteers by ultrasound and investigated potential risk factors for CE using a standardized questionnaire. Prevalence ratio (PR) with 95% confidence intervals (CI) was used to measure the association between CE and the factors investigated, applying bivariate and multivariate analyses. Results: Abdominal CE was detected in 42/892 screened volunteers (4.7%, 95% CI 3.2–6.1), only two of whom were under 15 years of age. Thirteen (30.9%) CE cases had 25 cysts in active stages (CE1, CE2, CE3a, according to the WHO Informal Working Group on Echinococcosis [WHO-IWGE] classification). The most relevant risk factors identified in the bivariate analysis included: living in rural areas (P = 0.003), age > 40 years (P = 0.000), always drinking water from natural sources (P = 0.007), residing in rural areas during the first 5 years of life (P = 0.000) and having lived more than 20 years at the current address (P = 0.013). In the multivariate final model, the statistically significant risk factors were: frequently touching dogs (P = 0.012), residing in rural areas during the first 5 years of life (P = 0.004), smoking (P = 0.000), age > 60 years (P = 0.002) and living in rural areas (P = 0.017). Conclusions: Our results point toward infection with CE being acquired since childhood and with constant exposure throughout life, especially in rural areas with a general environmental contamination. Keywords: Cystic echinococcosis, Echinococcus granulosus (s.l.), Ultrasound screening, Epidemiology, Risk factors

Cystic echinococcosis in dogs and children in the province of Río Negro, Argentina

Fil: Larrieu, Edmundo. Ministerio de Salud, Provincia de Río Negro, Viedma, Argentina; Facultad de Ciencias Veterinarias, Universidad Nacional de Río Negro; Argentina.  Fil: Seleiman, Marcos. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Herrero, Eduardo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Mujica, Guillermo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Labanchi, Jose Luis. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Araya, Daniel. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Grizmado, Claudia. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Sepulveda, Luis. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Calabro, Arnoldo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Talmon, Gabriel. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Crowley, Pablo. Ministerio de Salud, Provincia de Río Negro, Viedma, Argentina; Facultad de Ciencias Veterinarias, Universidad Nacional de Río Negro; Argentina.Fil: Albarracin, Silvina. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Arezo, Marcos. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: Volpe, Marcela. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Avila, A. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Perez, Alicia. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Uchiumi, Leonardo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Salvitti, Juan Carlos. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Santillan, Graciela. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Cystic echinococcosis (CE) is an endemic disease in the province of Río Negro, Argentina. The control program against CE has developed monitoring surveillance systems. Currently, the coproELISA/Western blot (WB) test is used to determine transmission in livestock farms (epidemiological units or EU) from collected dry field-dispersed dog feces. The objective was to evaluate the prevalence of CE on livestock farms and its relationship with CE cases in children aged 0-14 years. Canine fecal samples were obtained from randomly selected livestock farms and processed by the coproELISA/WB test. Furthermore, new cases in children in the same age group mentioned above were identified. In 278 EU, 571 samples of canine feces were obtained. There were 37 positive samples for coproELISA/WB (6.5%) and the presence of transmission was demonstrated in 37 EU (13.3%). There were no significant differences (p=0.9) with the survey conducted in the period 2003-2004 while there were significant differences (p=0.02) with the EU survey of native populations conducted in 2009-2010. With respect to animal density in the work area, the EU yielding negative results had an average of 2 dogs (SD 2.1) per EU while in the EU having positive results the average was 3 dogs (SD 4.2), showing statistically significant differences (p=0.02). In children under 15 years of age, 12 cases were diagnosed. This study has identified, on average, that the cases of hydatid disease are closer in the positive fields than in the negative fields (p=0.00307).The coproELISA/WB test allowed to identify the dispersion of CE on livestock farms and its relationship with the occurrence of cases in children in 2009-2010

Early Diagnosis, Treatment and Follow-Up of Cystic Echinococcosis in Remote Rural Areas in Patagonia: Impact of Ultrasound Training of Non-Specialists

Cystic echinococcosis (CE) is an important and widespread disease that affects sheep, cattle, and humans living in areas where sheep and cattle are raised. CE is highly endemic in rural sections of Rio Negro, Argentina, where our group is based. However, it requires continuous monitoring of both populations with human disease best assessed by means of ultrasound (US) screening. This is challenging in remote rural areas due to the shortage of imaging specialists. To overcome this hurdle, we set up a two-day training program of Focused Assessment with Sonography for Echinococcosis (FASE) on CE for family medicine practitioners with no previous experience in US. After the course, they were equipped with portable US scanners and dispatched to remote rural areas in Rio Negro where they screened patients, located and staged the cysts and decided on the treatment with the help of surgeons and radiologists in local tertiary care centers

Portadores asintomáticos de hidatidosis: epidemiología, diagnóstico y tratamiento Asymptomatic carriers of hydatidosis: epidemiology, diagnosis, and treatment

Hasta hace poco tiempo, la hidatidosis se consideraba un estado patológico de resolución exclusivamente quirúrgica. Sin embargo, en los últimos años se ha avanzado en los campos de la epidemiología, el diagnóstico y el tratamiento de la enfermedad y la nueva información aportada sobre la historia natural de la hidatidosis ha permitido definir nuevos criterios de atención. Ahora se sabe que hasta 67% de los portadores no sintomáticos de quistes hepáticos mantienen esa condición durante toda la vida. Esta situación genera resultados especiales en el inmunodiagnóstico. Así, la inmunoadsorción enzimática (ELISA) rinde una sensibilidad de 63% y una especificidad de 97% en portadores asintomáticos, mientras que la doble difusión cinco (DD5) tiene una sensibilidad de solo 31% en esos portadores. Por otra parte, los estudios por imágenes basados en la ecografía se han transformado en el método de elección para detectar a los portadores no sintomáticos. Son de 49 a 73% más sensibles que la serología e incluso pueden utilizarse como parte del sistema de vigilancia epidemiológica y del monitoreo de programas de control. También se han modernizado los esquemas de intervención. El tratamiento quimioterápico de portadores asintomáticos con albendazol produce hasta 69% de respuestas favorables, mientras que los tratamientos quirúrgicos mínimamente invasores como la punción-aspiración- inyección-reaspiración (PAIR) producen una reducción del volumen medio del quiste de hasta 66%. Estos factores han permitido instaurar un protocolo de tratamiento para portadores asintomáticos en los servicios hospitalarios de la Provincia de Río Negro, Argentina. Este se basa en el seguimiento de los quistes pequeños (tipo Ia de la escala de Gharbi modificada), tratamiento inicial con albendazol y con PAIR si no hay respuesta, en los quistes de mayor tamaño o complejidad (tipos Ib, II y III), y seguimiento de los quistes no vitales o muertos (tipos IV y V).<br>Until a short time ago, hydatidosis was considered a pathology that could only be resolved surgically. However, in recent years progress has been made with the epidemiology, diagnosis, and treatment of the disease, and new information on the natural history of hydatidosis has helped define new criteria for its treatment. It is now known that as many as 67% of the carriers of liver cysts who are asymptomatic remain so throughout their lives. This situation produces special results in immunologic testing. Enzyme-linked immunosorbent assay (ELISA) has a sensitivity of 63% and a specificity of 97% with asymptomatic carriers, while the double diffusion arc 5 test (DD5) achieves a sensitivity of only 31% with the same population. On the other hand, imaging studies based on ultrasonography have become the method of choice to detect asymptomatic carriers. Ultrasonography studies are 49% to 73% more sensitive than serological tests, and they can even be used as a part of epidemiological surveillance systems and to monitor control programs. Treatment schemes have also been modernized. Treating asymptomatic carriers chemotherapeutically with albendazole produces favorable results in as many as 69% of cases, while such minimally invasive surgical treatments as puncture-aspiration-injection-reaspiration (PAIR) reduce average cyst volume by as much as 66%. These factors have made it possible for hospital services in the province of Río Negro, Argentina, to establish a treatment scheme for asymptomatic carriers. It is based on the monitoring of small cysts (type Ia on the modified Gharbi scale); initial treatment with albendazole, followed by PAIR if there is no response, in larger or more complex cysts (types Ib, II, and III); and follow-up of inviable or dead cysts (types IV and V)

Vigilancia de la equinococosis quística en perros y niños en la provincia de Río Negro, Argentina

La equinococosis quística (EQ) es una enfermedad endémica en la provincia de Río Negro, Argentina. El programa de control de esta afección desarrolla sistemas de vigilancia epidemiológica basados en las técnicas de coproELISA/Western blot (WB) en muestras de heces de perros recolectadas del suelo, a fin de determinar establecimientos ganaderos (unidades epidemiológicas o UE) con transmisión presente. El objetivo de esta investigación fue evaluar la prevalencia de EQ en establecimientos ganaderos y su relación con la presencia de casos de EQ en niños de 0 a 14 años. Se seleccionaron aleatoriamente UE donde se obtuvieron muestras de materia fecal canina, las que fueron procesadas mediante coproELISA/WB. Asimismo, se identificaron casos nuevos ocurridos en niños del rango etario señalado. Se obtuvieron 571 muestras de 278 UE; 37 (6,5 %) fueron positivas a coproELISA/WB de 37 (13,3 %) UE con transmisión presente. Las diferencias con el relevamiento efectuado en el período 2003-2004 resultaron no significativas (p = 0,9), mientras que las diferencias con el relevamiento efectuado en UE de poblaciones originarias en 2009-2010 resultaron significativas (p = 0,02). Con relación a la densidad animal en el área de trabajo, las UE que dieron un resultado negativo tuvieron un promedio de 2 (DE: 2,1) perros por UE, en las UE con infección presente el promedio fue de 3 (DE 4,2), esta diferencia fue estadísticamente significativa (p = 0,02). Se diagnosticaron 12 casos en niños menores de 15 años. Se estableció que los casos de hidatidosis, en promedio, se situaron a menor distancia de los campos positivos a coproELISA/WB que de los campos negativos (p= 0,00307). La prueba de coproELISA/WB permitió identificar la dispersión de EQ en establecimientos ganaderos y analizar su relación con la ocurrencia de casos en niños

Health services of Rio Negro Province, Argentina.

<p>Health services of Rio Negro Province, Argentina.</p

Number, type and localization in CE carriers.

<p>Ultrasound surveys in children, Rio Negro, Argentina.</p><p>Footnotes:</p><p>WW: Watch and wait. ABZ: Albendazole. SURG: Surgery.</p><p>World Health Organization standardized classification of ultrasound pattern of cystic Echinococcosis (CE). CE1: unilocular cyst. CE2: multivesicular cyst. CE3a: detached membrane. CE3b multivesicular cyst with solid component. CE4: heterogenous pattern. CE5: calcified.</p><p>Note: 1 patient with 2 cysts may have 1 cyst <3 cm and 1>3 cm. The treatment listed by patient not by cyst. The same happens when a patient has 1 CE1 and 1 CE4 : the treatment is aimed at the former.</p

Pilot field trial of the EG95 vaccine against ovine cystic echinococcosis in Rio Negro, Argentina: 8 years of work

Fil: Larrieu, Edmundo. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina.Fil: Mujica, Guillermo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Araya, Daniel. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Labanchi, Jose Luis. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Arezo, Marcos. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Herrero, Eduardo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Santillán, Graciela. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: Vizcaychipi, Katherina A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: Uchiumi, Leonardo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Salvitti, Juan Carlos. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Grizmado, Claudia. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Calabro, Arnoldo. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Talmon, Gabriel. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Sepulveda, Luis. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Galvan, Jose María. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Cabrera, Marta. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: Seleiman, Marcos. Ministerio de Salud, Provincia de Río Negro; Argentina.Fil: Crowley, Pablo. Universidad Nacional de Río Negro. Escuela de Veterinaria; Argentina.Fil: Cespedes, Graciela. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: García Cachau, Mariela. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina.Fil: Gino, Lilia. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina.Fil: Molina, Leonardo. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina.Fil: Daffner, Jose. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Parasitología; Argentina.Fil: Gauci, Charles G. University of Melbourne. Faculty of Veterinary and Agricultural Sciences; Australia.Fil: Donadeu, Meritxell. University of Melbourne. Faculty of Veterinary and Agricultural Sciences; Australia.Fil: Lightowlers, Marshall W. University of Melbourne. Faculty of Veterinary and Agricultural Sciences; Australia.Cystic echinococcosis (CE) is endemic in the Rio Negro province of Argentina. After 30 years of control using praziquantel in dogs the transmission rate to humans and sheep has decreased significantly, however transmission persists. The objective of the study was to assess the inclusion of the EG95 for sheep in the control program and to determine the vaccine's operative feasibility in field conditions. An intervention study was defined in Rio Negro Province in Argentina comprising, in total, an area of 5820 Km2. Lambs received two vaccinations with the EG95 vaccine followed by a single booster injection when the animals were 1-1.5 years of age. Vaccination of lambs born into one trial site was introduced and continued for 8 years. Evidence for Echinococcus granulosus transmission was monitored before and after vaccination by coproantigen ELISA in faecal samples of dog, purgation of dogs to detect E. granulosus worms, necropsy on adult sheep and by ultrasound screening in children of 6-14 years old. 29,323 doses of vaccine were applied between 2009 and 2017, which a vaccination coverage of 80.1%/85.7% (57.3% average for fully vaccinated). Before the introduction of the vaccine 56.3% of the 6-year-old sheep were infected with E. granulosus at necropsy and 84.2% of the farms had infected sheep; 4.3% of the dogs were positive for E. granulosus infection using the arecoline test, and with coproELISA 9.6% of dog fecal samples were positive and 20.3% of the farms had infected dog.After the vaccine was introduced, 21.6% of sheep older than 6 years were found to be infected at necropsy and 20.2% of the farms were found to be infected; in dogs, 4.5% were found positive for E. granulosus using arecoline purgation and with coproELISA 3.7% of samples were positive, with 8.9% of farms having a positive dog. In 2016 only one case of E. granulosus infection was diagnosed by US screening in a 6-14 years old child. Included in the analysis are discussions of difficulties experienced in the field which affected correct vaccine administration as well as social features and practices that may impact on echinococcosis control and the EG95 vaccination program in Rio Negro. Vaccination of sheep with the EG95 vaccine provides a valuable new tool which improves the effectiveness of CE control activities. Vaccination was effective even in a difficult, remote environment where only approximately half the lambs born into the communities were fully vaccinated