Medical research and ethics - Revisited

Ethics in the medical research is known since many years; however, there have been new developments in this area recently. A phenomenal improvement in the health-care system, leading to increased life expectancy, and thereby, newer lifestyle and other health-related diseases has opened avenues for newer drugs and health-care technology. However, these have to be tried and tested in the context of the disease epidemiology, health-care delivery and of course, medical ethics. Monitoring and evaluation of the treatment regimes of well documented effective medicines is also required. This is the core of medical research. With the ever increasing concept of evidence-based medical system, and thereby, a rapid rise in the number of clinical trials; the role of medical ethics is potentially increasing to keep the patient

The Effects of Genetic and Pharmacologic Loss of the Notch4 Protein on Angiogenesis

Angiogenesis is the process by which new blood vessels form, as cells undergoing hypoxia secrete Vascular Endothelial Growth Factor (VEGF), which prompts a tip cell phenotype in adjacent endothelial cells. The new tip cell expresses DLL4 and presents it on its surface, which binds to Notch receptors on neighboring cells and inhibits them from also becoming tip cells, forcing them to adopt the stalk cell phenotype. Notch signaling is critical to the tip/stalk cell fate decision, and both Notch1 and Notch4 are expressed in the vasculature, but not much is known about the different roles and parallel functions of Notch4 in contrast to the well-studied Notch1. In order to quantify the effects of removing Notch4, Notch4 mutants were generated via genetic mutations, or Notch4 function was inhibited by an anti-Notch4 neutralizing antibody. The vasculature of postnatal retina from control animals was compared to either knockout or anti-Notch4 treated mice on measures of radial outgrowth, tip cell count, vascular density, large vessels count, and branching. The experimental groups were then compared to each other to understand the degree to which pharmacologic inhibition recapitulates the genetic knockout phenotype. Our data shows that the Notch4 genetic knockout mice tend to exhibit decreased radial outgrowth and reduced branching. This supports the hypothesis that Notch1 and Notch4 have unique targets, as Notch1 knockouts show a stark increase in tip cell density, which is not seen in Notch4 genetic knockouts. In contrast, the pharmacologic Notch4 knockouts resembled the Notch4 genetic knockouts in radial outgrowth, but Notch1 mutants in tip cell density, though the reason why is not yet known. The mapping of angiogenic pathways is of consequence because it offers many avenues for studying human health. For example, new cancer research aims to reduce blood flow to tumors by decreasing angiogenesis, and published data suggests that knocking out Notch4 reduces tumor perfusion and growth. Therefore, a deeper understanding of the role of Notch4, and in turn, angiogenesis, could aid the development of new medicinal therapies for some of our most deadly diseases

Assessment of quality of life in Indian patients with vitiligo, an observational study

Background: Vitiligo is the most common hypopigmentary disorder. In India, the incidence of vitiligo is 0.25-2.5%. It considerably influences the patient’s quality‑of‑life (QoL) and psychological well‑being.Methods: A prospective, observational study was conducted from April 2016 to September 2016 in dermatology outpatient department. Patients clinical characteristic were noted and Quality of life was assessed by using Vitiligo Quality of Life Questionnaires [VQLQ]. During item development, none of the questions were changed according to the results of cognitive and understand ability testing. The scale consisted of 25 questions. The answer to each question was scored as ‘never = 1’, ‘sometimes = 2’, ‘often = 3’ and ‘all the time = 4’, so the total score ranged between 25 and 100. Higher scores represented more severely impaired quality of life.Results: We enrolled 78 Vitiligo patients who were attending dermatology department for phototherapy. Out of them 53 were female. Mean age was 37.12±12.270. Most common age group was 31-40 years. Mean VLQL score 40.92±6.081. Patients were divided based on VQLQ score in Moderate (50-75) and Low score group (25-50). Vitiligo patients presented with symptoms of pain, irritation and itching (P<0.0001). Vitiligo patients when assessed for feeling domain were significantly embarrassed for their overall look and appearance. (P < 0.0001). When Personal relationship domain was analysed physical contact was a major concern (P <0.002). Patients suffering from Vitiligo were significantly worried about spread of vitiligo and occurrence of cancer (P<0.0001). Therapy for Vitiligo was time consuming time and was a work place challenge for the patients (P <0.0001). The reliability of VQLQ in our study was Cronbach’s α coefficient was 0.876.Conclusions: QoL impairment was relatively high in vitiligo patients. Medical intervention and counselling should focus to improve feelings, personal relationship, anxiety, school/work, leisure and symptom domains

Evaluation of invitro Antimutagenic Potential of Lagenaria Siceraria Using Ame’s Test

Cancer is one of the most life-threatening diseases and widespread in both developed and developing countries. Accumulation of genetic alterations is main etiology for cancer developments. Many of the Cucurbitaceae plants possess antitumor activity traditionally. Methanolic extract of Lagenaria siceraria Standley Fruit was tested for their antimutagenic potential. The extract of plant exhibited varying level of antimutagenicity. Ames test was used in the current study to evaluate antimutagenic activity in TA98 and TA100 strains of Salmonella typhimurium using direct (Sodium azide) acting mutagens. Results of the study showed significant antimutagenicity against mutagen in TA98 and TA100 strains. The antimutagenicity of the extract observed in the present study implies chemopreventive pharmacological importance of Lagenaria siceraria Standley Fruit and encourages its use as a functional food

ESTIMATION OF LERCANIDIPINE BY FIRST DERIVATIVE UV SPECTROSCOPY

A simple, accurate, economical, fast and reliable method for the determination of lercanidipine (LR) is highly desirable to support formulation screening and quality control. The method was developed for determination of LR in pure drug and tablet dosage form. Best results were shown in terms of linearity, accuracy, precision, LOD and LOQ for pure drug as well as for tablets. UV absorbance was measured at 332 nm. Excellent linearity (correlation coefficient (r2) = 0.9970) found in the concentration range of 7.5-60 μg/ml. The LOD and LOQ were 1.0770 and 3.2638 μg/ml respectively and good recoveries were achieved (95.779%)

Remedial Prospective of Hippophae rhamnoides Linn. (Sea Buckthorn)

Sea buckthorn (Hippophae rhamnoides L.) constitutes thorny nitrogen fixing deciduous shrub. Sea buckthorn(SBT) is primarily valued for its very rich vitamins A, B1, B12, C, E, K, and P; flavonoids, lycopene, carotenoids, and phytosterols. and therapeutically important since it is rich with potent antioxidants. Scientifically evaluated pharmacological actions of SBT are like inflammation inhibited by reduced permeability, loss of follicular aggregation of lymphocytes from the inflamed synovium and suppress lymphocyte proliferation. SBT-reduced recurrence of angina, ischemic electrocardiogram which might be due to decreased myocardial oxygen consumption and inhibition of platelet aggregation induced by collagen. SBT can kill both cancer cells of S180, P388, SGC7901 and lymphatic leukemia (L1200). The antiulcer activity may be related to reduce gastric empty time, inhibiting proteolytic activity and promoting wound reparation processes of mucosa. SBT exerts antihypertensive effect in part by blocking angiotensin-2 receptor on cell surface. SBT decreased the level of stress hormones and enhanced hypoxic tolerance in animals indicating its anti-stress, adaptogenic activity. A lot of research work is still needed to find cellular and molecular mechanisms of these activities and also yet to be explored for its activity in osteoporosis, hemorrhage, cataract, urinary stone, acne, psoriasis, polyneuritis, cheilosis, glossities, baldness, anti-obesity, gout, and chronic prostitis

Corrections to the Nonrelativistic Ground Energy of a Helium Atom

Considering the nuclear motion, the authors give out the nonrelativistic ground energy of a helium atom by using a simple but effective variational wave function with a flexible parameter $k$. Based on this result, the relativistic and radiative corrections to the nonrelativistic Hamiltonian are discussed. The high precision value of the helium ground energy is evaluated to be -2.90338 a.u., and the relative error is 0.00034%.Comment: 8 pages, no figures, 2 table

Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response

The paradigm for macrophage characterization has evolved from the simple M1/M2 dichotomy to a more complex model that encompasses the broad spectrum of macrophage phenotypic diversity, due to differences in ontogeny and/or local stimuli. We currently lack an in-depth pan-cancer single cell RNA-seq (scRNAseq) atlas of tumour-associated macrophages (TAMs) that fully captures this complexity. In addition, an increased understanding of macrophage diversity could help to explain the variable responses of cancer patients to immunotherapy. Our atlas includes well established macrophage subsets as well as a number of additional ones. We associate macrophage composition with tumour phenotype and show macrophage subsets can vary between primary and metastatic tumours growing in sites like the liver. We also examine macrophage-T cell functional cross talk and identify two subsets of TAMs associated with T cell activation. Analysis of TAM signatures in a large cohort of immune checkpoint inhibitor-treated patients (CPI1000 + ) identify multiple TAM subsets associated with response, including the presence of a subset of TAMs that upregulate collagen-related genes. Finally, we demonstrate the utility of our data as a resource and reference atlas for mapping of novel macrophage datasets using projection. Overall, these advances represent an important step in both macrophage classification and overcoming resistance to immunotherapies in cancer

Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients

Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies

Brain Tumor Segmentation and Tractographic Feature Extraction from Structural MR Images for Overall Survival Prediction

This paper introduces a novel methodology to integrate human brain connectomics and parcellation for brain tumor segmentation and survival prediction. For segmentation, we utilize an existing brain parcellation atlas in the MNI152 1mm space and map this parcellation to each individual subject data. We use deep neural network architectures together with hard negative mining to achieve the final voxel level classification. For survival prediction, we present a new method for combining features from connectomics data, brain parcellation information, and the brain tumor mask. We leverage the average connectome information from the Human Connectome Project and map each subject brain volume onto this common connectome space. From this, we compute tractographic features that describe potential neural disruptions due to the brain tumor. These features are then used to predict the overall survival of the subjects. The main novelty in the proposed methods is the use of normalized brain parcellation data and tractography data from the human connectome project for analyzing MR images for segmentation and survival prediction. Experimental results are reported on the BraTS2018 dataset.Comment: 14 pages, 5 figures, 4 tables, accepted by BrainLes 2018 MICCAI worksho