LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

Bulk chemotherapy and drug release strategies for cancer treatment have been associated with lack of specificity and high drug concentrations that often result in toxic side effects. This work presents the results of an experimental study of cancer drugs (prodigiosin or paclitaxel) conjugated to Luteinizing Hormone-Releasing Hormone (LHRH) for the specific targeting and treatment of triple negative breast cancer (TNBC). Injections of LHRH-conjugated drugs (LHRH-prodigiosin or LHRH-paclitaxel) into groups of 4-week-old athymic female nude mice (induced with subcutaneous triple negative xenograft breast tumors) were found to specifically target, eliminate or shrink tumors at early, mid and late stages without any apparent cytotoxicity, as revealed by in vivo toxicity and ex vivo histopathological tests. Our results show that overexpressed LHRH receptors serve as binding sites on the breast cancer cells/tumor and the LHRH-conjugated drugs inhibited the growth of breast cells/tumor in in vitro and in vivo experiments. The inhibitions are attributed to the respective adhesive interactions between LHRH molecular recognition units on the prodigiosin (PGS) and paclitaxel (PTX) drugs and overexpressed LHRH receptors on the breast cancer cells and tumors. The implications of the results are discussed for the development of ligand-conjugated drugs for the specific targeting and treatment of TNBC

Ethnic minority disparities in progression and mortality of pre-dialysis chronic kidney disease : a systematic scoping review

Background: There are a growing number of studies on ethnic differences in progression and mortality for pre-dialysis chronic kidney disease (CKD), but this literature has yet to be synthesised, particularly for studies on mortality. Methods: This scoping review synthesized existing literature on ethnic differences in progression and mortality for adults with pre-dialysis CKD, explored factors contributing to these differences, and identified gaps in the literature. A comprehensive search strategy using search terms for ethnicity and CKD was taken to identify potentially relevant studies. Nine databases were searched from 1992 to June 2017, with an updated search in February 2020. Results: 8059 articles were identified and screened. Fifty-five studies (2 systematic review, 7 non-systematic reviews, and 46 individual studies) were included in this review. Most were US studies and compared African-American/Afro-Caribbean and Caucasian populations, and fewer studies assessed outcomes for Hispanics and Asians. Most studies reported higher risk of CKD progression in Afro-Caribbean/African-Americans, Hispanics, and Asians, lower risk of mortality for Asians, and mixed findings on risk of mortality for Afro-Caribbean/African-Americans and Hispanics, compared to Caucasians. Biological factors such as hypertension, diabetes, and cardiovascular disease contributed to increased risk of progression for ethnic minorities but did not increase risk of mortality in these groups. Conclusions: Higher rates of renal replacement therapy among ethnic minorities may be partly due to increased risk of progression and reduced mortality in these groups. The review identifies gaps in the literature and highlights a need for a more structured approach by researchers that would allow higher confidence in single studies and better harmonization of data across studies to advance our understanding of CKD progression and mortality

TERRE project : interplay between unsaturated soil mechanics and low-carbon geotechnical engineering

The geotechnical construction industry is a major component of the overall construction sector and is strategically important in infrastructure development (transportation, flood and landslide protection, building foundations, waste disposal). Although industry and research in the overall construction sector have been investing significantly in recent years to produce innovative low-carbon technologies, little innovation has been created in geotechnical construction industry, which is lagging behind other construction industry sectors. This paper discusses the interplay between low-carbon geotechnical engineering and unsaturated soil mechanics based on the research carried out within the project TERRE (Marie Skłodowska-Curie Innovative Training Networks funded by the European Commission, 2015-2019,H2020-MSCA-ITN-2015-675762)

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Molecular detection of Coxiella burnetii infection in small mammals from Moshi Rural and Urban Districts, northern Tanzania

Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a zoonotic disease of public health importance. In northern Tanzania, Q fever is a known cause of human febrile illness, but little is known about its distribution in animal hosts. We used a quantitative real‐time PCR (qPCR) targeting the insertion element IS1111 to determine the presence and prevalence of C. burnetii infections in small mammals trapped in 12 villages around Moshi Rural and Moshi Urban Districts, northern Tanzania. A total of 382 trapped small mammals of seven species were included in the study; Rattus rattus (n = 317), Mus musculus (n = 44), Mastomys natalensis (n = 8), Acomys wilson (n = 6), Mus minutoides (n = 3), Paraxerus flavovottis (n = 3) and Atelerix albiventris (n = 1). Overall, 12 (3.1%) of 382 (95% CI: 1.6–5.4) small mammal spleens were positive for C. burnetii DNA. Coxiella burnetii DNA was detected in five of seven of the small mammal species trapped; R. rattus (n = 7), M. musculus (n = 1), A. wilson (n = 2), P. flavovottis (n = 1) and A. albiventris (n = 1). Eleven (91.7%) of twelve (95% CI: 61.5–99.8) C. burnetii DNA positive small mammals were trapped within Moshi Urban District. These findings demonstrate that small mammals in Moshi, northern Tanzania are hosts of C. burnetii and may act as a source of C. burnetii infection to humans and other animals. This detection of C. burnetii infections in small mammals should motivate further studies into the contribution of small mammals to the transmission of C. burnetii to humans and animals in this region

Development of Experimental Techniques and an Analytical Model for Aluminum Nitriding

The rates of diffusion of nitrogen into aluminum and the subsequent formation of aluminum nitride are unclear. By matching experimental data to analytical models one can gain a better understanding of the diffusion process for nitrogen into aluminum and formation of aluminum nitride. We combine novel experimental and modeling approaches to achieve this goal. We develop a technique for in situ measurement of nitrogen deposition using a microbalance and present a simple reaction diffusion equation to simulate the diffusion of nitrogen into aluminum and subsequent precipitation into aluminum nitride. A mixed boundary condition formulation is presented to account for the initial influx of nitrogen at the surface until a saturation level is reached. We curve fit the derived model equations to the experimental data and determine the system diffusion coefficient and reaction rate constant

Developing Empirical Models for Estimating Photosynthetically Active Radiation over Akure, South Western, Nigeria

In this study, the measured monthly average daily global solar radiation and extraterrestrial solar radiation using the generalized 45% and 40% dataset was utilized to estimate the photosynthetically active radiation (PAR) and extraterrestrial photosynthetically active radiation (PAR0) for Akure (Latitude 7.170N, Longitude 5.180E, and 375.0 m above sea level) Ondo State located in South Western, Nigeria. The monthly average daily sunshine hours, maximum and minimum temperature data were used to develop nine (9) new PAR sunshine based models and three (3) PAR temperature-based models. The meteorological parameters used in this study covered a period of thirty-one years (1980 – 2010). The newly developed models were tested using statistical indicators of the coefficient of determination (R2), Mean Bias Error (MBE), Root Mean Square Error (RMSE), Mean Percentage Error (MPE), t-test, Nash – Sutcliffe Equation (NSE) and Index of Agreement (IA). The PAR sunshine based models that took a quadratic form and the linear logarithmic PAR temperature-based models were found more suitable for estimating PAR for the location under study. Comparing the PAR sunshine based and temperature-based models indicated that the PAR sunshine based model is more suitable for PAR estimation in Akure. Furthermore, the results showed that PAR is high during the dry season and low during the rainy season. Based on the measured and estimated PAR models; the minimum values were found in July and August while the maximum values in February, March and November. The descriptive statistical analysis shows that the PAR and all the estimated sunshine based PAR data spread out more to the left of their mean value (negatively skewed). Similarly, they have negative kurtosis which indicates a relatively flat distribution and the possibility of platykurtic distribution. The PAR and the PAR logarithmic temperature-based model (equation 17a) data spread out more to the left of their mean value (negatively skewed), while the PAR linear exponent and linear temperature-based models (equation 17b and 17c) data spread out more to the right of their mean value (positively skewed). The PAR and all the estimated PAR temperature-based data have negative kurtosis which indicates a relatively flat distribution and the possibility of platykurtic distribution