The relationship between the effects of teratogens in vivo and in vitro

The effects of the selected agents, insulin, diphenylhydantoin, chloroquine sulphate, chlordiazepoxide HC1, meprobamate, cobaltous chloride and lead nitrate, on the development of chick embryos and on the morphological and biochemical differentiation of cells in culture were investigated. The cultures were established from neural retina, limb and kidney fibroblasts derived from 8-day old chick embryos, and lens epithelium from day -old chicks.In in vivo studies, insulin treatment caused limb, beak, tail and eye defects. Chlordiazepoxide HC1 caused growth retardation, especially of the. limbs. Cobaltous chloride induced lens opacity and thin limbs and lead nitrate caused spinal and brain damage. The incidence and the degree of the defects depended both on the stage of treatment and the amount of the agents administered. In contrast, diphenylhydantoin, chloroquine sulphate and meprobamate did not induce any detectable gross morphological abnormality.In cell culture studies, insulin treatment of cultured lens epithelial and neural retina cells affected both the synthesis and accumulation of several protein components. The effect of insulin on lens epithelial cells was found to vary with the genotype. The effect of insulin on limb fibroblast cell cultures was dependent on the level of FCS in the culture medium. Chlordiazepoxide HC1 treatment of cultured cells affected the synthesis and accumulation of the proteins in neural retina, limb and kidney fibroblast cells. Diphenylhydantoin treatment affected protein synthesis and accumulation in lens epithelial and neural retina 'cell cultures. Chioroquine sulphate treatment affected protein synthesis and accumulation in lens epithelial, neural retina and brain cell cultures. Diphenylhydantoin,chloroquine sulphate and chlordiazepoxide HC1 also affected the activity of choline acetyl transferase in neural retina cell cultures. Lead nitrate was found to affect protein synthesis and accumulation only in neural retina cell cultures. Finally meprobamate affected protein synthesis and accumulation in limb fibroblast cell cultures.The data suggest that certain correlations do exist between in vivo and in vitro teratogenic tests

Clinical usefulness of epicardial adipose tissue in patients with high-intermediate pre-test probability for coronary artery disease

Background: Epicardial adipose tissue (EAT) is thought to be associated with the extension and severity of coronary artery disease (CAD), and echocardiographic measurement of EAT thickness is considered to be a possible cardiovascular risk indica­tor. The European Society of Cardiology Task Force recommends further non-invasive testing in patients with an intermediate pre-test probability (PTP) for the diagnosis of CAD. Aim: We sought to evaluate the clinical usefulness of performing EAT measurements in patients with a high-intermediate PTP. Methods: Patients referred to an outpatient clinic with stable chest pain symptoms, with PTP for CAD between 66% and 85%, were included in the study. Echocardiographic measurement of the EAT was identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium. Single-photon emission computed tomography (SPECT) was performed in all patients. The diagnosis of CAD was based on the presence of reversible perfusion defects on SPECT. Results: A total of 126 patients (76 men, 60.3%) with a mean age of 65.3 ± 9.1 years were recruited. The EAT thickness was 7.3 ± 0.7 mm in patients with positive SPECT and 6.2 ± 0.6 mm in patients with negative SPECT (p < 0.001). Multivariable analysis revealed higher rates of positive SPECT in patients with higher EAT (odds ratio [OR] 9.80; 95% confidence interval [CI] 3.72–25.79; p < 0.001), and receiver operating characteristic curve analysis showed that the greatest specificity was obtained when the cut-off value of EAT thickness was 6.75 mm (sensitivity 76%; specificity 74%). Conclusions: In patients with high-intermediate PTP, EAT is a useful measurement that may assist in risk stratification

Cancer therapy shapes the fitness landscape of clonal hematopoiesis.

Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies

Cancer therapy shapes the fitness landscape of clonal hematopoiesis.

Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation

NFC Technology Based Secure Virtual Cash Shopping Architecture Design

With the proliferation of shopping, the diversification of patterns of payment has been inevitable. Recently, Near Field Communication (NFC) was included in the list of new patterns of payment which are implemented by many different technologies. In this study, it is aimed to apply different types of security measures taken against various attack types targeting NFC based virtual shopping systems to the architecture that we developed. The virtual shopping system is a real-time site-management application enabling the occupants to easily pay dues in virtue of their NFC-based mobile application. A hybrid model was developed for the security of the NFC-based system. The response performance of the system was calculated by means of some tests and compared to other studies in literature

Contrast−induced monoplegia following coronary angioplasty with iopromide

Seizures, alterations in mental and cerebral functions, and ophthalmoplegia are known side effects of contrast agents. Here we report a case of self-limiting monoplegia in a patient after the administration of intracoronary iopromide after coronary angiography which emphasises that, although benign, contrast-induced monoplegia is a neurological disease which requires careful evaluation and accurate management.Seizures, alterations in mental and cerebral functions, and ophthalmoplegia are known side effects of contrast agents. Here we report a case of self-limiting monoplegia in a patient after the administration of intracoronary iopromide after coronary angiography which emphasises that, although benign, contrast-induced monoplegia is a neurological disease which requires careful evaluation and accurate management

Somatic Embryogenesis of Populus deltoides

Node, internode, and leaf explants of Populus deltoides Bartr. ex Marsh. x Populus deltoides Bartr. ex Marsh. hybrid poplar clone (89 M 066) tissue culture regenerated plantlets were used for direct and indirect somatic embryogenesis. Direct somatic embryos were differentiated on node, internode and leaf explants on Murashige and Skoog basal medium (MS) supplemented with N-6-Benzyladenine (BA) and 2,4-Dichlorophenoxy acetic acid (2,4-D). The best somatic embryogenesis observed on MS medium supplemented with 0.05 mg/l BA and 5 mg/l 2,4-D with internodes explants in darkness within 3 weeks. Embryogenic calli formation for the first step of indirect regeneration were obtained on node, internode and leaf explants on MS with 2,4-D or MS with 1-Phenyl-3-(1,2,3-thiadiazol-5-yl) urea (TDZ) and Coconut Water (CW). Internode explants gave the best result (100%) for embryogenic calli formation on MS with 0.8 or 1 mg/l TDZ with 2% CW after 3 weeks. Subsequent transfer of internode-derived embryogenic calli on the same media resulted in somatic embryogenesis within 2 weeks with the frequency of 33% on MS with 0.8 mg/l TDZ with 2% CW. Further development of embryos to the torpedo stage was obtained by subculturing on the same medium. There after, germination of the direct somatic embryos were achieved on Woody Plant Medium (WPM) supplemented with 1 mg/l zeatine in 3 weeks. Data in the study were subjected to statistical evaluation. These systems could be useful for rapid clonal propagation via somatic embryogenesis of eastern cottonwood clones