Square-Planar Alkylidyne-Osmium and Five-Coordinate Alkylidene-Osmium Complexes: Controlling the Transformation from Hydride-Alkylidyne to Alkylidene

Square-planar alkylidyne and five-coordinate alkylidene mixed iPr3P–Os–IPr (IPr = 1, 3-bis(diisopropylphenyl)imidazolylidene) complexes have been discovered and characterized, and their formation has been rationalized. The cationic five-coordinate hydride-alkylidyne compounds [OsHX(=CPh)(IPr)(PiPr3)]OTf (X = Cl (1), F (4); OTf = CF3SO3) undergo deprotonation with KOtBu to afford the trans-halide-alkylidyne square-planar derivatives OsX(=CPh)(IPr)(PiPr3) (X = Cl (2), F (5)). Oxidative addition of the C(sp)–H bond of phenylacetylene and methyl propiolate along the Cl–Os–CPh axis of 2 with the hydrogen atom directed to the alkylidyne leads to alkynyl-cis-hydride-alkylidyne intermediates, which rapidly evolve into the five-coordinate alkylidene complexes Os(C=CR)Cl(-CHPh)(IPr)(PiPr3) (R = Ph (6), CO2Me (7)) as a consequence of the migration of the hydride from the metal center to the Ca atom of the alkylidyne. Oxidative addition of the C(sp)–H bond of methyl propiolate along the X–Os–CPh axis of 2 and 5 with the hydrogen atom directed to the halide gives the alkynyl-trans-hydride-alkylidyne derivatives OsH(C=CCO2Me)X(=CPh)(IPr)(PiPr3) (X = Cl (8), F (9)). Complex 8 evolves into 7. However, complex 9 containing the stronger p-donor fluoride is stable. The oxidative addition of HCl to 2 selectively yields the cis-hydride-alkylidyne compound OsHCl2(=CPh)(IPr)(PiPr3) (10), which is also stable

Implementation research for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva infection prevention and control (IPC)-think tank (part 1)

Background Around 5–15% of all hospital patients worldwide suffer from healthcare-associated infections (HAIs), and years of excessive antimicrobial use in human and animal medicine have created emerging antimicrobial resistance (AMR). A considerable amount of evidence-based measures have been published to address these challenges, but the largest challenge seems to be their implementation. Methods In June 2017, a total of 42 experts convened at the Geneva IPC-Think Tank to discuss four domains in implementation science: 1) teaching implementation skills; 2) fostering implementation of IPC and antimicrobial stewardship (AMS) by policy making; 3) national/international actions to foster implementation skills; and 4) translational research bridging social sciences and clinical research in infection prevention and control (IPC) and AMR. Results Although neglected in the past, implementation skills have become a priority in IPC and AMS. They should now be part of any curriculum in health care, and IPC career paths should be created. Guidelines and policies should be aligned with each other and evidence-based, each document providing a section on implementing elements of IPC and AMS in patient care. International organisations should be advocates for IPC and AMS, framing them as patient safety issues and emphasizing the importance of implementation skills. Healthcare authorities at the national level should adopt a similar approach and provide legal frameworks, guidelines, and resources to allow better implementation of patient safety measures in IPC and AMS. Rather than repeating effectiveness studies in every setting, we should invest in methods to improve the implementation of evidence-based measures in different healthcare contexts. For this, we need to encourage and financially support collaborations between social sciences and clinical IPC research. Conclusions Experts of the 2017 Geneva Think Tank on IPC and AMS, CDC, and WHO agreed that sustained efforts on implementation of IPC and AMS strategies are required at international, country, and hospital management levels, to provide an adequate multimodal framework that addresses (not exclusively) leadership, resources, education and training for implementing IPC and AMS. Future strategies can build on this agreement to make strategies on IPC and AMS more effective

Mad2 overexpression promotes aneuploidy and tumorigenesis in mice

Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes

Las aves como factor de riesgo de arbovirosis en la provincia de Buenos Aires

St. Louis Encephalitis and West Nile viruses are arboviruses maintained in an enzootic cycle among birds by mosquitoes of the genus Culex. Both diseases have been reported in humans and evidence of infection have been identified in birds and horses in temperate Argentina. To advance in risk estimation, a bibliographic review of all published works in the country was carried out in order to know the potential host (only antibodies) and competent (able to amplify the virus) bird species. Then, the geographic distribution of bird species involved in their transmission cycles was characterized in Buenos Aires Province at two spatial scales: coarse grain potential host bird species occurrence maps for each virus (input Aves Argentinas), and fine grain density and percentage maps for each competent species (input eBird). The number of potential host bird species was higher in the northeast and southwest of the province for both viruses. Fine grain maps showed similar distribution and density patterns for all competent species, with maximums in the northeast and southeast, being Eared Dove the species with the highest density and percentage of sightings. Human cases records generally matched with high values areas in coarse grain maps and with high percentage cells in Eared Dove and House Sparrow fine grain maps. These results are a novel input for the elaboration of transmission risk maps and vigilance of these arbovirosis.Los virus de la Encefalitis de San Luis y del Oeste del Nilo son arbovirus que se mantienen en un ciclo enzoótico entre aves por mosquitos del género Culex. En la Argentina templada, ambas enfermedades han sido reportadas en humanos y se han registrado evidencias de infección en aves y caballos. Para avanzar en la estimación del riesgo, se realizó una revisión bibliográfica de todos los trabajos publicados en el país para conocer las especies de aves potencialmente hospedadoras (sólo anticuerpos) y competentes (capaces de amplificar el virus). Luego, la distribución geográfica de las especies de aves implicadas en sus ciclos de transmisión fue caracterizada en la provincia de Buenos Aires a 2 escalas espaciales: mapas de ocurrencia de especies de aves potencialmente hospedadoras para cada virus a grano grueso (fuente Aves Argentinas), y mapas de densidad y porcentaje para cada especie competente a grano fino (fuente eBird). El número de especies de aves potencialmente hospedadoras fue mayor en el noreste y sudoeste de la provincia para ambos virus. Los mapas de grano fino mostraron patrones de distribución y densidad similares, con máximos en el noreste y sudeste, siendo la torcaza la especie con mayor densidad y porcentaje de avistamientos. Los registros de casos humanos coincidieron en general con las áreas de valores altos en los mapas de grano grueso y con las celdas con alto porcentaje en los mapas de grano fino de torcaza y gorrión. Estos resultados son un primer aporte para la estimación del riesgo de transmisión y vigilancia de estas arbovirosis

Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas.

Altered expression of the retinoblastoma (RB) tumour-suppressor gene product (pRB) has been detected in sporadic bone and soft-tissue sarcomas. Earlier studies, analysing small cohorts of sarcoma patients, have suggested that these alterations are more commonly associated with high-grade tumours, metastatic lesions and poorer survival. This study was designed to re-examine the prevalence and clinical significance of altered pRB expression in a large and selected group of soft-tissue sarcomas from 174 adult patients. Representative tissue sections from these sarcomas were analysed by immunohistochemistry using a well-characterised anti-pRB monoclonal antibody. Tumours were considered to have a positive pRB phenotype only when pure nuclear staining was demonstrated, and cases were segregated into one of three groups. Group 1 (n = 36) were patients whose tumours have minimal or undetectable pRB nuclear staining (< 20% of tumour cells) and were considered pRB negative. Patients with tumours staining in a heterogeneous pattern (20-79% of tumour cells) were classified as group 2 (n = 99). The staining of group 3 (n = 39) was strongly positive with a homogeneous pRB nuclear immunoreactivity (80-100% of tumour cells). pRB alterations were frequently observed in both low- and high-grade lesions. Altered pRB expression did not correlate with known predictors of survival and was not itself an independent predictor of outcome in the long-term follow-up. These findings support earlier observations that alterations of pRB expression are common events in soft-tissue sarcomas; nevertheless, long-term follow-up results indicate that altered patterns of pRB expression do not influence clinical outcome of patients affected with soft-tissue sarcomas. It is postulated that RB alterations are primary events in human sarcomas and may be involved in tumorigenesis or early phases of tumour progression in these neoplasias

Age and socio-economic status affect dengue and COVID-19 incidence: Spatio-temporal analysis of the 2020 syndemic in Buenos Aires City

In early 2020, Argentina experienced the worst dengue outbreak in its history, concomitant with first-to-date increasing COVID-19 cases. Dengue epidemics in temperate Argentina have already been described as spatially heterogeneous; in the previous 2016 outbreak, transmission occurred 7.3 times more frequently in slums compared to the rest of Buenos Aires City (CABA). These informal settlements have deficient sanitary conditions, precarious housing and high incidence of social vulnerabilities. The purpose of this work was to study the spatio-temporal patterns of the 2020 dengue epidemic in CABA in relation to socio-economic living conditions of its inhabitants and its interaction with the onset of COVID-19. The study considered the period between Jan 1st and May 30th 2020. Dengue and COVID-19 databases were obtained from the National Health Surveillance System; each record was anonymized and geo-localized. The city was divided according to census tracts and grouped in four socio-economic strata: slums, high, mid and low residential. An aligned-rank transform ANOVA was performed to test for differences in the incidence of dengue and COVID-19, and age at death due to COVID-19, among socio-economic strata, four age categories and their interaction. The incidence by cluster was calculated with a distance matrix up to 600 m from the centroid. Spatial joint dengue and COVID-19 risk was estimated by multiplying the nominal risk for each disease, defined from 1 (low) to 5 (high) according to their quantiles. During the study period, 7,175 dengue cases were registered in CABA (incidence rate 23.3 cases per 10,000 inh), 29.2% of which occurred in slums. During the same period, 8,809 cases of COVID-19 were registered (28.6 cases per 10,000 inh); over half (51.4%) occurred in slums, where the median age of cases (29 years old) was lower than in residential areas (42 years old). The mean age of the deceased was 58 years old in slums compared to 79 years old outside. The percentage of deaths in patients under 60 years old was 56% in slums compared to 8% in the rest of the city. The incidence of both diseases was higher in slums than in residential areas for most age categories. Spatial patterns were heterogeneous: dengue presented higher incidence values in the southern sector of the city and the west, and low values in highly urbanized quarters, whereas COVID-19 presented higher values in the east, south, high populated areas and slums. The lowest joint risk clusters were located mainly in high residential areas, whereas high joint risk was observed mainly in the south, some western clusters, the historical part of the city and center north. The social epidemiological perspective of dengue and COVID-19 differed, given that socio environmental heterogeneity influenced the burden of both viruses in a different manner. Despite the overwhelming effect of the COVID-19 pandemic, health care towards other diseases, especially in territories with pre-existing vulnerabilities, should not be unattended.Fil: Carbajo, Anibal Eduardo. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Cardo, María Victoria. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Pesce, Martina. Ministerio de Salud de la Nación; ArgentinaFil: Iummato, Luciana E.. Ministerio de Salud de la Nación; ArgentinaFil: Bárcena Barbeira, Pilar. Ministerio de Salud de la Nación; ArgentinaFil: Santini, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Utgés, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentin

Is autumn the key for dengue epidemics in non endemic regions? The case of Argentina

Background. Dengue is a major and rapidly increasing public health problem. In Argentina, the southern extreme of its distribution in the Americas, epidemic transmission takes place during the warm season. Since its re-emergence in 1998 two major outbreaks have occurred, the biggest during 2016. To identify the environmental factors that trigger epidemic events, we analyzed the occurrence and magnitude of dengue outbreaks in time and space at different scales in association with climatic, geographic and demographic variables and number of cases in endemic neighboring countries. Methods. Information on dengue cases was obtained from dengue notifications reported in the National Health Surveillance System. The resulting database was analyzed by Generalized Linear Mixed Models (GLMM) under three methodological approaches to: identify in which years the most important outbreaks occurred in association with environmental variables and propose a risk estimation for future epidemics (temporal approach); characterize which variables explain the occurrence of local outbreaks through time (spatio-temporal approach); and select the environmental drivers of the geographical distribution of dengue positive districts during 2016 (spatial approach). Results. Within the temporal approach, the number of dengue cases country-wide between 2009 and 2016 was positively associated with the number of dengue cases in bordering endemic countries and negatively with the days necessary for transmission (DNT) during the previous autumn in the central region of the country. Annual epidemic intensity in the period between 1999-2016 was associated with DNT during previous autumn and winter. Regarding the spatio-temporal approach, dengue cases within a district were also associated with mild conditions in the previous autumn along with the number of dengue cases in neighboring countries. As for the spatial approach, the best model for the occurrence of two or more dengue cases per district included autumn minimum temperature and human population as fixed factors, and the province as a grouping variable. Explanatory power of all models was high, in the range 57-95%. Discussion. Given the epidemic nature of dengue in Argentina, virus pressure from endemic neighboring countries along with climatic conditions are crucial to explain disease dynamics. In the three methodological approaches, temperature conditions during autumn were best associated with dengue patterns. We propose that mild autumns represent an advantage for mosquito vector populations and that, in temperate regions, this advantage manifests as a larger egg bank from which the adult population will re-emerge in spring. This may constitute a valuable anticipating tool for high transmission risk events.Fil: Carbajo, Anibal Eduardo. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cardo, María Victoria. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guimarey, Pilar Consuelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Lizuain, Arturo Andrés. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Buyayisqui, María Pía. Ministerio de Salud de la Nación; ArgentinaFil: Varela, Teresa. Ministerio de Salud de la Nación; ArgentinaFil: Utgés, Maria E.. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Giovacchini, Carlos. Ministerio de Salud de la Nación; ArgentinaFil: Santini, Maria Soledad. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.

To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways

Estimated Risk of HIV Acquisition and Practice for Preventing Occupational Exposure: A Study of Healthcare Workers at Tumbi and Dodoma Hospitals, Tanzania.

Health care workers (HCWs) are at risk of acquiring human immuno-deficiency virus (HIV) and other infections via exposure to infectious patients' blood and body fluids. The main objective of this study was to estimate the risk of HIV transmission and examine the practices for preventing occupational exposures among HCWs at Tumbi and Dodoma Hospitals in Tanzania. This study was carried out in two hospitals, namely, Tumbi in Coast Region and Dodoma in Dodoma Region. In each facility, hospital records of occupational exposure to HIV infection and its management were reviewed. In addition, practices to prevent occupational exposure to HIV infection among HCWs were observed. The estimated risk of HIV transmission due to needle stick injuries was calculated to be 7 cases per 1,000,000 HCWs-years. Over half of the observed hospital departments did not have guidelines for prevention and management of occupational exposure to HIV infections and lacked well displayed health and safety instructions. Approximately, one-fifth of the hospital departments visited failed to adhere to the instructions pertaining to correlation between waste materials and the corresponding colour coded bag/container/safety box. Seventy four percent of the hospital departments observed did not display instructions for handling infectious materials. Inappropriate use of gloves, lack of health and safety instructions, and lack of use of eye protective glasses were more frequently observed at Dodoma Hospital than at Tumbi Hospital. The poor quality of the hospital records at the two hospitals hampered our effort to characterise the risk of HIV infection acquisition by HCWs. Greater data completeness in hospital records is needed to allow the determination of the actual risk of HIV transmission for HCWs. To further reduce the risk of HIV infection due to occupational exposure, hospitals should be equipped with sufficient personal protective equipment (PPE) and HCWs should be reminded of the importance of adhering to universal precautions