Expanding global health opportunities for UK-based interventional radiology trainees.

AIMS: As the future workload of interventional radiologists in the UK continues to expand, it is imperative that current IR trainees are given maximal opportunities to expand their skill sets. This paper argues that opportunities for involvement in international collaborative fieldwork should be expanded for interventional radiology trainees in the UK, as a means of maximising their future competency and positive contribution to the advancement of global healthcare. The study builds upon first-hand experience of the authors in the field and a review of the relevant literature. MATERIALS AND METHODS: This scoping review aimed to ascertain the current global health opportunities for interventional radiology trainees primarily in Resource Limited Countries (RLCs). This review further contrasted these opportunities with ones provided to trainees within North America and European countries. RESULTS: This review found that the opportunities for international collaborative fieldwork for UK interventional radiology trainees are sparse. The availability of such opportunities in the US is significantly greater as is the awareness and appreciation of the benefits of such international collaborations for trainees. Benefits include greater experience with a variety of pathologies, a potentially larger volume of workload, improved cultural competency and proficiency and greater cost-conscious and more sustainable practices. It is also pertinent that any future global partnership opportunities for UK clinicians are crafted with care to benefit both UK and international healthcare professionals, institutions and patients within RLCs. CONCLUSION: Significant work is needed to expand opportunities for global health for interventional radiology trainees in the UK. It is incumbent upon the major radiology societies and educational bodies within the UK to expand upon such opportunities to develop a robust, world-leading workforce, which would subsequently enhance our global health positionality and reflexivity.

Design, synthesis, cytotoxic, and anti-inflammatory activities of some novel analogues of aloe-emodin isolated from the rhizomes of Rheum emodi.

In connection with our continuous efforts in the synthesis of derivatives from major compounds isolated from traditional medicinal plants, in the present study we have attempted to synthesize the furan-conjugated aloe-emodin derivatives (5a-j) using a three-component reaction. The synthesized derivatives were assessed for anticancer activity against five different cancer cell lines using the in vitro MTT assay and the results showed that most of the derivatives are potent against cancer cells comparing with the control. Compounds 5a and 5e showed excellent activity against all the cancer cells with less than 12.5 µM and arrested the cell cycle at the G0/G1 phase in both CAL27 and SCC9 cells. Compound 5e induces the early apoptosis in CAL27 cells and compounds 5a and 5e induce early and late apoptosis, respectively, in SCC9 cells. Moreover, compounds 5b, 5c, 5i, and 5j showed excellent anti-inflammatory activity in LPS-stimulated RAW 264.7 cells by inhibiting IL-6 production. The molecular docking studies revealed that compound 5e has strong interaction with the CLK kinase and protein kinase II through hydrogen binding Asp325 and Lys290.

Enhanced antimicrobial, antioxidant and anticancer activity of Rhizophora apiculata: An experimental report.

The present study is designed to evaluate the antimicrobial, antioxidant and anticancer activities of Rhizophora apiculata. Initially, the phenolic and flavonoid content was quantified in solvent extracts, and gallic acid and rutin were used as a control, respectively. Further, antimicrobial and minimal inhibitory activities of different solvent extracts were assessed against human clinical pathogenic bacteria, and the results showed that butanol and methanol extract has potential antimicrobial activity. FTIR analysis of solvent extracts showed the presence of phenolic compounds at 3409-3430 cm-1 that actively involved in various applications including antioxidant and anticancer activities. The in vitro antioxidant activity of solvent extracts showed excellent antioxidant potential, about 84% of DPPH free-radical scavenging, 76% of hydrogen peroxide, 82% of hydroxyl radical scavenging, and 80% of reducing power. Two-way ANOVA analysis showed that the highly significant effect of antioxidant activity depends on the concentration of extracts. The DNA protection efficiency of extracts against oxidative damage was confirmed by DNA nicking assay using bacterial DNA. The methanol extract effectively inhibited the growth and induces the apoptosis through ROS generation and sensitizes the mitochondrial membrane potential of A549 lung cancer cells. Taken together, the results showed that the solvent extracts of R. apiculata could be potential antioxidant and anticancer agents.

Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing.

Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.

Expression of cytokine-mRNA in peripheral blood mononuclear cell of human immunodeficiency virus-1 subtype C infected individuals with opportunistic viral infections from India (South).

Human immunodeficiency virus (HIV) disease progression is associated with a marked change in the level of plasma cytokines. The study reported here investigated the level of mRNA expression of different cytokines: Tumour necrosis factor-alpha (TNF-α), interferon (INF)-gamma, interleukin-10 (IL-10) and IL-21 in the peripheral blood mononuclear cell among the antiretroviral therapy naive subtype C HIV-1 infected individuals and normal healthy controls by real time polymerase chain reaction. The mRNA expressions of all the 4 cytokines in HIV-1 infected individuals were significantly higher compared to healthy controls (P value range 0.0004-0.01). The mean level of IL-10, INF-gamma and TNF-α were higher in HIV infected individuals with low CD4 counts (<300 cells/µl). The IL-10 expression showed a significant negative correlation with CD4 counts (r=-0.25, P=0.04) while IL-21 showed a positive correlation with CD4 counts (r=0.26, P=0.03). There was a significant negative correlation between the cytomegalovirus (CMV) viral load and IL-21 expression. Cytokine levels by mRNA detection avoids the inherent problem of measuring plasma level and this study also provide information on the cytokine levels and CD4+ T cell level among HIV-1 subtype C infected individuals with opportunistic viral infections like CMV.

Frequency of Epstein--Barr virus infection as detected by messenger RNA for EBNA 1 in histologically proven gastric adenocarcinoma in patients presenting to a tertiary care center in South India.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinoma is a relatively uncommon entity detected in approximately 10% of gastric adenocarcinoma. OBJECTIVE: The purpose of this study is to estimate the frequency of EBV-associated gastric carcinoma and also to assess the nature of presentation, any significant difference between this subgroup and EBV-negative gastric adenocarcinomas with respect to age and sex predilection, lymph nodal status, site of presentation. MATERIALS AND METHODS: We prospectively analyzed 100 cases of gastric adenocarcinoma who underwent either a partial or total gastrectomy during the period from March 2010 to August 2011. The tumour and the corresponding normal gastric tissue from the same patient were analyzed for the presence of Epstein-Barr nuclear antigen 1 (EBNA1) messenger ribonucleic acid (mRNA) by real-time polymerase chain reaction (PCR). RESULT: EBV was detected in 6% cases of gastric adenocarcinoma. All the positive patients were males. The majority of cases involved the proximal stomach and there was variable lymph nodal involvement. CONCLUSION: Our study endorses that there is an association between EBV infection and gastric adenocarcinoma in the Indian population. There was no significant difference between this subgroup and EBV-negative gastric adenocarcinomas with respect to age and sex predilection, lymph nodal status and site of presentation. Short-term follow-up of this subgroup of patients seems to indicate a good overall prognosis after appropriate treatment. However, a larger study with long-term follow-up is needed to further establish the role of EBV in gastric adenocarcinoma in this study population.

Emergence of HIV-1 drug-resistant variants in women following antiretroviral prophylaxis for the prevention of mother to child transmission.

PURPOSE: Emergence of drug resistance following HIV prophylaxis has an important impact on ART program. OBJECTIVE: To investigate the emergence of drug resistance in HIV-1 infected pregnant women. MATERIALS AND METHODS: Fifty-three HIV-1 infected pregnant women who had received 4-12 weeks of antenatal AZT followed by Nevirapine during delivery and Combivir [AZT + 3TC] for 1 week postpartum (group-1, n = 48) or who come at the time of delivery and received Nevirapine followed by Combivir for 1 week (group-2, n = 5) were recruited. Samples were collected prior to the start of the prophylaxis and 5-8 weeks postpartum. In addition, a third sample was collected between 26-65 weeks postpartum from 7 women. Amplification of HIV-1 pol gene and drug resistance analysis was done. RESULT: Two (3.8%) women in group-1 showed transmitted drug resistance and they continued to show this even at 6 weeks postpartum. One (2%) woman from group-1 showed a mutation after 6-8 weeks of prophylaxis. Among the samples collected between 26-65 weeks postpartum, 3/7 (43%) showed mutations and all these women belong to group-1. Women belonging to group-2 didn't show mutation prior to or following prophylaxis. CONCLUSION: In contrast to the available data among pregnant women with ART prophylaxis, our data showed reduced frequency of mutations following 5-8 weeks of postpartum but an emergence of mutation later (26-65 weeks). The addition of Combivir with the single dose Nevirapine during delivery and the early stage of the disease with higher CD4 counts could be the reasons for this.

Biosynthesis of silver nanoparticles from deep sea bacterium Pseudomonas aeruginosa JQ989348 for antimicrobial, antibiofilm, and cytotoxic activity.

Pseudomonas aeruginosa (JQ989348) was isolated from deep sea water sample and used for synthesis of silver nanoparticles (AgNPs). AgNPs were confirmed by analyzing surface plasmon resonance using UV-visible spectrophotometer at 420 nm. Further scanning electron microscope analysis confirmed the range of particle size between 13 and 76 nm and XRD pattern authorizes the anisotropic crystalline nature of AgNPs. Fourier transform infrared spectrum endorsed the presence of high amount of proteins and other secondary metabolites in synthesized AgNPs influence the reduction process and stabilization of nanoparticles. The inhibitory activity of AgNPs was tested against human pathogens showed high activity against Eschericia coli, Vibrio cholerae, Aeromonas sp., and Cornebacterium sp. demonstrating its antimicrobial value against pathogenic diseases. Additionally, biologically synthesized AgNPs have notable anti-biofilm activity against primary biofilm forming bacteria P. aeruginosa and Staphylococcus aureus. The MTT assay method was evaluated using human cervical cancer cells exposed the AgNPs have excellent cytotoxic activity.

Acute ischemic stroke in aortic dissection: case report and review of literature.

The estimated incidence of aortic dissection ranges from 5 to 30 cases per million per year. Nearly 38% of cases are missed at an initial presentation due to the wide range of clinical symptoms. We report a survivor of an inadvertent thrombolysis in acute ischemic stroke, secondary to aortic dissection.

Effect of mercuric chloride on circulating hormones in adult albino rats.

The effect of mercuric chloride at two different doses, 0.5 mg/kg body weight (low dose), 1 mg/kg body weight (high dose), for 30 days, was seen on the circulating hormones in the mature male albino rats. Testosterone level was markedly decreased in the low dose (P < 0.01) and high dose (P < 0.001) treated animals. The level of luteinizing hormone (LH) was also reduced in the low dose (P < 0.01) as well as in the high dose (P < 0.001) treated animals. However, follicle stimulating hormone (FSH) and prolactin (PRL) levels were found to be decreased only in the high dose (P < 0. 05) treated animals and no change was observed in the low dose treated animals. The changes in the hormone levels caused by the mercuric chloride treatment suggest the dysfunction of pituitary-testicular axis.

Effect of mercuric chloride on membrane-bound enzymes in rat testis.

AIM: To study the effect of mercuric chloride on the membrane-bound enzymes. METHODS: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane-bound enzymes in the testis of adult albino rats. RESULTS: Mercuric chloride significantly decreased the body weight and testis weight in the high dose group (P< 0.05), but not in the low dose group. The activities of 5'nucleotidase and adenosine triphosphatases were markedly decreased (P< 0.01) in the testis of both groups. Alkaline phosphatase and ggr-glutamyl transferase activities were significantly increased (P< 0.01) in both groups. However, the effect was more pronounced in the high than in the low dose groups. CONCLUSION: The dose dependent effect of mercuric chloride on these enzymes may affect the membrane characteristics and thereby the fertility of the animal.

Preliminary crystallographic studies of the ligand-binding domain of the thyroid hormone receptor complexed with triiodothyronine.

A truncated, recombinant form of the thyroid hormone receptor, including the hormone binding domain, has been co-crystallized with the hormone T3. The crystals are monoclinic, most likely space group P2, with two molecules per asymmetric unit and cell dimensions a = 63.6 A, b = 80.8 A, c = 100.9 A and beta = 92.1 degrees. The crystals diffract to only medium resolution and decay rapidly in the X-ray beam using laboratory sources. By contrast, high resolution, high-quality data are obtained using synchrotron radiation in conjunction with cryocrystallography.

Enzymes of carbohydrate metabolism in human breast carcinoma: relationship with serum hormones.

The enzymes involved in carbohydrate metabolism and their relationship with circulating estradiol (ET2) and prolactin (Prl) were studied in premenopausal and postmenopausal women with fibroadenoma and carcinoma of breast. The activities of all the glycolytic enzymes studied were increased in breast carcinoma tissues except for glyceraldehyde-3-phosphate dehydrogenase which showed decreased activity. Among the glycolytic enzymes studied, hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase were found to be stimulated by elevated levels of serum ET2 and further stimulated by a simultaneous increase in Prl. However, the activity of lactate dehydrogenase was more specifically stimulated by Prl rather than ET2. None of the glycolytic enzymes studied was altered in fibroadenoma breast tissues.

Plasma membrane enzymes in human breast carcinoma: relationship with serum hormones.

Alkaline phosphatase, 5'nucleotidase and gammaglutamyl transferase were studied in premenopausal and post-menopausal women with fibroadenoma and breast carcinoma tissues. The relationship of circulating estradiol (E2) and prolactin (Prl) with these enzymes was also investigated. All the three enzyme activities were found to be elevated in the breast carcinoma tissues of both pre- and postmenopausal groups. None of the membrane bound enzymes studied was altered in fibroadenoma breast tissues. The activities of all the three enzymes in breast carcinoma tissues were stimulated by the elevated level of serum Prl and further stimulated by a simultaneous increase in E2.

Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase.

The structure of isocitrate dehydrogenase [threo-DS-isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42] from Escherichia coli has been solved and refined at 2.5 A resolution and is topologically different from that of any other dehydrogenase. This enzyme, a dimer of identical 416-residue subunits, is inactivated by phosphorylation at Ser-113, which lies at the edge of an interdomain pocket that also contains many residues conserved between isocitrate dehydrogenase and isopropylmalate dehydrogenase. Isocitrate dehydrogenase contains an unusual clasp-like domain in which both polypeptide chains in the dimer interlock. Based on the structure of isocitrate dehydrogenase and conservation with isopropylmalate dehydrogenase, we suggest that the active site lies in an interdomain pocket close to the phosphorylation site.

Serum hormones in human breast cancer subjects.

Different serum hormones were studied in patients with benign breast diseases and breast carcinoma in respect of different phases of the menstrual cycle, as well as in postmenopausal women. In premenopausal breast carcinoma subjects 10% showed elevated serum estradiol alone, 7% showed elevated serum prolactin alone, and 12% subjects exhibited elevated levels of both serum estradiol and prolactin. Similarly, in postmenopausal breast carcinoma subjects 12% showed elevated serum estradiol alone, 10% showed elevated serum prolactin alone, and 22% exhibited elevated level of both serum estradiol and prolactin. On the other hand, in patients with benign breast disease only 5 showed an elevated level of prolactin alone. More than 50% of premenopausal women with carcinoma of the breast had low level of serum progesterone during the luteal phase as compared to normal subjects. No variations in serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were evident between normal subjects and women with breast carcinoma or benign breast disease. The increased level of serum estradiol and prolactin may be useful in the diagnosis of human breast cancer.