A study of the properties, reactivity and anticancer activity of novel N- methylated-3-thiazolyl or 3-thienyl carbazoles and their Pd(II) and Pt(II) complexes

The synthesis and characterization of two hybrid N-methylated carbazole derivatives containing a thiazolyl or a thienyl ring is reported. The thiazolyl derivative has been also characterised by X-ray diffraction analysis. The study of its reactivity in front of [MCl2(dmso)(2)] (M = Pd or Pt) or Na-2[PdCl4] in methanol has allowed us to isolate and characterize its complexes. However, for the thienyl analogue, the formation of any Pd(II) or Pt(II) complex was not detected, indicating that it is less prone to bind to the M(II) ions than its thiazolyl analogue. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) calculations have also been carried out in order to rationalize the influence of the nature of the thiazolyl or thienyl group on the electronic delocalization. Molecular mechanics calculations show that the free rotation of the thiazolyl in relation to the carbazole requires a greater energy income than for its thienyl analogue. Studies of the cytotoxic activity of the new compounds on colon (HCT116) and breast (MDA-MB231 and MCF7) cancer cell lines show that the thiazolyl carbazole ligand and its Pt(II) complex are the most active agents of the series and in the MCF7 line their potency is higher than that of cisplatin. In the non-tumoral human skin fibroblast BJ cell line, all the compounds were less toxic than cisplatin. Their potential ability to modify the electrophoretic mobility of pBluescript SK+ plasmid DNA and to act as inhibitors of Topoisomerases I and II alpha or cathepsin B has also been investigated

Desarrollo y validación de modelo 3D para entrenamiento laparoscópico en ginecología: más allá de la caja de entrenamiento convencional

Introducción: El entrenamiento en cirugía laparoscópica mejora la formación del ginecólogo, por lo que realizar repetidamente ejercicios que emulen condiciones que se presentan en la cirugía, debería mejorar la curva de aprendizaje. Objetivo: Proponer un modelo de simulador físico 3D para el entrenamiento en residentes de cirugía laparoscópica, mínimamente invasiva y de piso pélvico del servicio de ginecología del Centro Médico Docente La Trinidad, periodo enero-noviembre de 2021. Metodología: Se realizó un trabajo descriptivo, con modalidad de proyecto factible, fundamentado en el desarrollo un simulador físico para el entrenamiento del programa de formación de cirugía laparoscópica ginecológica y de piso pélvico, se basó en la evaluación técnica y científica de las necesidades del proceso de entrenamiento por medio de una encuesta. Resultados: Todos los encuestados afirmaron que los simuladores o cajas de entrenamiento laparoscópica son necesarias para la formación inicial del cirujano y se debe de disponer de al menos uno en el servicio de ginecología. Todos los encuestados afirmaron que las características ergonómicas cambian en la cirugía ginecológica en comparación con otros tipos de cirugías y el 90,0% afirmó que es pertinente diseñar un modelo simulador para entrenamiento en cirugía laparoscópica ginecológica. Todos los encuestados confirmaron que los simuladores son importantes y deben ser lo más realista posible para el entrenamiento de habilidades y destrezas en laparoscopia ginecológica. Conclusión: Se demuestra la necesidad de disponer de modelos de entrenamiento en los programas de formación con la finalidad de minimizar los riesgos inherentes a la cirugía en pacientes en vivo

Sífilis congénita: Diagnóstico, tratamiento y prevención oportuna, en México.

Objective: Development of reference material for the diagnosis, treatment and timely prevention of both gestational and congenital syphilis in Mexico, in order to implement the recommendations and updates of this sexually transmitted disease. Methods: In this project, we reviewed scientific studies, articles, case reports, as well as national and international legal documents, in order to gather relevant and current information. Results: Syphilis is a systemic disease caused by the spirochete type bacterium Treponema Pallidum of chronic evolution and it is often asymptomatic. It can be sexually or vertically transmitted, so it is determined as acquired or congenital.  In Mexico, congenital syphilis remains a public health problem, even though it is a preventable and treatable disease. Conclusion:Nowadays, syphilis is considered a rigorously controlled pathology. However, there has been a significant increase in cases despite the widespread availability of basic treatment. We must be objective when identifying the failures in the assistance provided to the pregnant women during their prenatal care, to improve the quality of health services, in favor of the well-being of the mother and the fetus, thus avoiding the associated complications such as: preterm birth, low birth weight, intrauterine fetal death and neonatal death, among others.Objetivo: Desarrollo de material de consulta para el diagnóstico, tratamiento y prevención oportuna de la Sífilis tanto gestacional y congénita en México, con el fin de aplicar las recomendaciones y actualizaciones de esta enfermedad de transmisión sexual. Métodos: En este proyecto se revisaron bibliografías de estudios científicos,  artículos, reportes de caso, además de documentos legales nacionales e internacionales, con el fin de recabar la información relevante y actual. Resultados: Sífilis es una enfermedad sistémica causada por la bacteria de tipo espiroqueta Treponema Pallidum de evolución crónica y muchas veces asintomática. Es transmitida por vía sexual o materno fetal, por lo cual se determina como adquirida o congénita.  En México la sífilis congénita sigue siendo un problema de salud pública, aunque es una enfermedad prevenible y tratable. Conclusión: Hoy en día, la sífilis se considera una patología estrechamente controlada. Sin embargo, se ha observado un incremento significativo de casos, a pesar de la  disponibilidad generalizada de tratamiento base. Se debe ser objetivo al identificar las fallas en la asistencia prestada a las embarazadas  durante su atención prenatal, para así mejorar la calidad de los servicios de salud en favor del bienestar de la madre y el feto, evitando las complicaciones asociadas como: parto pretérmino, bajo peso al nacer, muerte fetal intrauterina y muerte neonatal, entre otros

Epigenetic Regulation of HIV-1 Latency by Cytosine Methylation

Human immunodeficiency virus type 1 (HIV-1) persists in a latent state within resting CD4+ T cells of infected persons treated with highly active antiretroviral therapy (HAART). This reservoir must be eliminated for the clearance of infection. Using a cDNA library screen, we have identified methyl-CpG binding domain protein 2 (MBD2) as a regulator of HIV-1 latency. Two CpG islands flank the HIV-1 transcription start site and are methylated in latently infected Jurkat cells and primary CD4+ T cells. MBD2 and histone deacetylase 2 (HDAC2) are found at one of these CpG islands during latency. Inhibition of cytosine methylation with 5-aza-2′deoxycytidine (aza-CdR) abrogates recruitment of MBD2 and HDAC2. Furthermore, aza-CdR potently synergizes with the NF-κB activators prostratin or TNF-α to reactivate latent HIV-1. These observations confirm that cytosine methylation and MBD2 are epigenetic regulators of HIV-1 latency. Clearance of HIV-1 from infected persons may be enhanced by inclusion of DNA methylation inhibitors, such as aza-CdR, and NF-κB activators into current antiviral therapies

Does the pharmacy expenditure of patients always correspond with their morbidity burden? Exploring new approaches in the interpretation of pharmacy expenditure

<p>Abstract</p> <p>Background</p> <p>The computerisation of primary health care (PHC) records offers the opportunity to focus on pharmacy expenditure from the perspective of the morbidity of individuals. The objective of the present study was to analyse the behaviour of pharmacy expenditure within different morbidity groups. We paid special attention to the identification of individuals who had higher values of pharmacy expenditure than their morbidity would otherwise suggest (i.e. outliers).</p> <p>Methods</p> <p>Observational study consisting of 75,574 patients seen at PHC centres in Zaragoza, Spain, at least once in 2005. Demographic and disease variables were analysed (ACG^®8.1), together with a response variable that we termed 'total pharmacy expenditure per patient'. Outlier patients were identified based on boxplot methods, adjusted boxplot for asymmetric distributions, and by analysing standardised residuals of tobit regression models.</p> <p>Results</p> <p>The pharmacy expenditure of up to 7% of attendees in the studied PHC centres during one year exceeded expectations given their morbidity burden. This group of patients was responsible for up to 24% of the total annual pharmacy expenditure. There was a significantly higher number of outlier patients within the low-morbidity band which matched up with the higher variation coefficient observed in this group (3.2 vs. 2.0 and 1.3 in the moderate- and high-morbidity bands, respectively).</p> <p>Conclusions</p> <p>With appropriate validation, the methodologies of the present study could be incorporated in the routine monitoring of the prescribing profile of general practitioners. This could not only enable evaluation of their performance, but also target groups of outlier patients and foster analyses of the causes of unusually high pharmacy expenditures among them. This interpretation of pharmacy expenditure gives new clues for the efficiency in utilisation of healthcare resources, and could be complementary to management interventions focused on individuals with a high morbidity burden.</p

Up in smoke? The impact of smog on risk perception and satisfaction of international tourists in Beijing

The topic of concern of this research is smog, and the destination of interest is Beijing, China. The present study investigated the attitudes and behaviours of international on‐site tourists to the worrying issue of smog in China's capital. The work is embedded in previous theoretical and conceptual studies of risk and hazard perception. Social and natural disasters affecting tourism are widely reported in various media formats (Kozak et al., 2007). Tourism research concerning such disasters has become an important concern of tourism analysis (Reisinger & Mavondo, 2005; Tan & Tang, 2013). Previous studies have tended to explore attitudinal and behavioural patterns of people who plan to travel, thus concentrating on their decision‐making processes. However, tourists' risk perception and in turn their moderating strategies may change according to different stages across the travel consumption sequence (Choi et al., 2012). Therefore, it is necessary to investigate tourists' risk perception in different travel stages including pre‐travel decision making, on‐site reactions and post‐trip recollections (Mansfeld, 2006). By focusing on smog – a relatively persistent and somewhat predictable form of hazard – and accessing tourists' on‐site views, the present study may illuminate the existing studies of tourist risk perception. In the past two years, dangerous smog conditions have been experienced in most cities in China. Smog is a frequently visible, sometimes literally tangible, generic term for air pollution deriving from multiple human activities including but not limited to the burning of fossil fuels and industrial processes (Watts, 2010). The National Disaster Relief Department of China has listed smog as a natural disaster due to the rising numbers of deaths attributed directly to severe incidents of the problem. Further, the overall harmful effects of smog on human health justify public concern and research interest (Bickerstaff & Walker, 1999; Semenza et al., 2008). According to Tasci and Boylu (2010), disasters (and smog can now be included in the list of disasters) exert immediate and continuing effects on tourist choices through affecting a destination's image. Such effects are dramatically enhanced when the topic of concern is frequently reported in mass media. The available statistical data show declines in inbound and domestic tourists visiting the worst smog‐affected areas in China. Beijing is the Chinese city with perhaps the most serious and widely publicized smog conditions. It is also one of China's most popular tourist destinations. The city and its region have been one of the hardest‐hit locations in terms of the frequency of smog and the severity of fine particle matter in the atmosphere. However, there has been very limited research directly exploring the impact of smog on tourists. Tourists' decision‐making, in terms of choosing this destination, and their travel experiences in smog‐affected cities such as Beijing have not been considered. It is generally accepted that understanding tourists' concerns, including their anxiety about health and safety issues, are of paramount importance to travel destinations (Kozak et al., 2007; Law, 2006). Building on these concerns, this research analysed the views of international tourists travelling to Beijing. The present research has three broad objectives: 1. To explore international tourists' overall and specific concerns with the issue of smog in Beijing; 2. To examine whether there are associations among key tourist attitudes and perceptions including smog concern, risk perception, tourist satisfaction and intention to return to Beijing. 3. To consider whether the relationships found for risk in other content areas also exist for smog. In meeting these objectives, the work seeks to provide conceptual linkages and explore theoretical connections among key influential variables rather than simply describing tourists' concern about smog. Additionally, the marketing and management consequences of this study and allied research are portrayed

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO--Virgo data

We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO--Virgo run in the detector frequency band $[10,2000]\rm~Hz$ have been used. No significant detection was found and 95$\%$ confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about $7.6\times 10^{-26}$ at $\simeq 142\rm~Hz$. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass -- boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC.Comment: 25 pages, 5 figure

Constraints on the cosmic expansion history from GWTC-3

We use 47 gravitational-wave sources from the Third LIGO-Virgo-KAGRA Gravitational-Wave Transient Catalog (GWTC-3) to estimate the Hubble parameter $H(z)$, including its current value, the Hubble constant $H_0$. Each gravitational-wave (GW) signal provides the luminosity distance to the source and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and $H(z)$. The source mass distribution displays a peak around $34\, {\rm M_\odot}$, followed by a drop-off. Assuming this mass scale does not evolve with redshift results in a $H(z)$ measurement, yielding $H_0=68^{+12}_{-7} {\rm km\,s^{-1}\,Mpc^{-1}}$ ($68\%$ credible interval) when combined with the $H_0$ measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the $H_0$ estimate from GWTC-1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event's potential hosts. Assuming a fixed BBH population, we estimate a value of $H_0=68^{+8}_{-6} {\rm km\,s^{-1}\,Mpc^{-1}}$ with the galaxy catalog method, an improvement of 42% with respect to our GWTC-1 result and 20% with respect to recent $H_0$ studies using GWTC-2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about $H_0$) is the well-localized event GW190814