Breast cancer and serum ferritin - Menopausal status perspective: Menopause - A fickle determinant

Background: Association of raised serum ferritin levels with breast carcinoma is a well established fact on account of iron enhanced free radical mediated oestrogen induced carcinogenesis. Previous literatures report variations in serum ferritin levels with menopause, especially indicating its association with metabolic syndrome in post-menopausal women. Seldom has any study focussed upon influence of age and menopausal status towards serum ferritin level determination in breast cancer patients. Assess an impact of age and menopausal status over serum ferritin levels in patients with breast cancer and in healthy females; and their comparisons. Methods: Enzyme linked immuno-sorbent assay based estimation of serum ferritin was carried out in patients with breast carcinoma and healthy females. Objective: Age-wise and menopausal status-wise grouped numerical data were analyzed through intra- and inter-group comparisons.Results: Higher serum ferritin levels were observed in all age groups as well as pre-menopausal and post-menopausal groups of breast cancer subjects than their respective groups among healthy subjects. No particular age or menopausal status-wise pattern could be identified among cases as well as healthy controls.Conclusions: Serum ferritin levels abide no obvious influence of age or menopausal status in breast cancer patients as well as post-menopausal women devoid of metabolic syndrome. The present study reiterates the possible role of iron in breast carcinogenesis.

Gender-Associated Oral and Periodontal Health Based on Retrospective Panoramic Radiographic Analysis of Alveolar Bone Loss

Gender-based heterogeneity in periodontal disease has been witnessed in the recent past with huge mounting evidence. The composite effect of sex-based genetic structure and the sex steroid hormones runs in line with the corresponding gender-related differences in risk for chronic periodontitis. Since estrogens, the predominant sex hormones in women, show immune protective and anti-inflammatory effects in hormonally active premenopausal women, they show better periodontal status compared to age-matched men. Conversely, after menopause with a weakening estrogen signal, women may show an equal or even more serious periodontal status compared to men. Periodontal status of postmenopausal women may be improved by menopausal hormone therapy. Alveolar bone loss, an irreversible sign of past periodontal disease activity can be easily observed on radiographs in an objective manner. Orthopantomographs provide a fairly accurate assessment of the status of alveolar bone in the whole mouth. A cross-sectional retrospective panoramic radiographic analysis has been carried out in a north Indian dental institute to decipher the gender-based distribution of periodontal bone loss. The current chapter shall provide an update on gender-based differences in oral health, underlying mechanisms, differences in patterns and distribution of alveolar bone loss (case study), and potential gender-specific disease protection and management strategies

Equation of Craft in India

Description ‘Equation of Craft in India’ is a design research project of Craft Future Lab, NID Ahmedabad, India under the collaborative effort of the International Centre for Indian Craft (ICIC), Dept. of Lifestyle Accessory Design (LAD), and Design for Social Innovation and Sustainability Lab (NID DESIS Lab). The project was initiated and led by Prof. Amresh Panigrahi with his fellow 16 Master level Design students of the Department of LAD batch 2018 with the prime objective of attempting to understand the current dynamics in the Indian craft sector. The origin of crafts goes a long way back, to the Indus Valley civilization. It had its fair share of evolution through the centuries that followed from the Vedic, Mauryan, Mughal periods to the British colonization and the onset of industrialization. The crafts of India have gone through several impactful events with our relatively newfound Independent democratic country and its political and economic development. The current context of craft in the 20th century takes into account the social, economic and geopolitical setting of India with the presence of various global developments in technology, import-export scenario, travel and popular mass ideas. Here the System mapping is an attempt to represent the identified components and variables and interrelationship within the current system understanding of the craft sector in India. Craft in its essence Craft is a vital source of identity for the craftsman as it derived its meaning by its local acceptance in its socio-cultural fabric. It has developed through a long line of rich cultural heritage. The function of crafts varies from being utilitarian, ornamental to finding purposes in religious, ritualistic, and festival purposes. Crafts now are much more susceptible to cross-cultural influences of the increasing spread of media, the internet, and education. The Development Commissioner of Handicrafts (DCH), India defined crafts as ‘items made by hand, often with the use of simple tools and generally artistic and traditional. They include objects of utility and objects of decoration’. The three main confluence for the creation of a craft comes with (a) an artisan along with his ability working on (b) the raw materials with a little help from the (c) simple tools that aids where human abilities limit him. The craftsmen and the craft dynamics The four significant divisions of craftsmen based on their ability are – Master-craftsmen, Craftsmen, Apprentice, and newly joined. Master-craftsmen display the highest skill and bring novelty in the craft. Apart from the newly joined category of artisans, all other craftsmen majorly learn the craft from the master craftsperson or from within the family itself, passed down through the generations. It is a labour-intensive sector where artisans get less return in terms of money, recognition, value for craft for the much more investment they put into it. The investment may be in terms of effort, time, and the number of workforces. The real success of a craft is no more confined to the ability of the craftsperson’s skills, raw material and tools. It is the time that demands the market knowledge to make the craft a success. However, the craftsman abilities are currently limited with less market knowledge and mostly restricted to the boundaries of his craft understanding. Lack of knowledge, their struggle with the craft practices and its continuity became much more complicated, which forced them to switch to other jobs or to want a different life for their children. Initiatives at organising the sector The craft & cottage industry is the most significant non-agricultural decentralized sector of the Indian economy. In the wake of the government’s attempt to organize the sector and tap into its full potential, it works on multiple value chains of the craft sector. The government provides market platforms through multiple exhibitions, Haats, fairs and emporiums, wherein efforts are put into making the customer realize the cultural context of the craft. One of the major competitors in the market remains to be the mass-produced industrialized products flooding in domestically and also via imports from other neighbouring countries. Domestically, authentic craft loses its market to mass-produced fake craft due to its comfortable, cheaper availability. Protection of crafts ingenuity The fake market affected the craftsmen and the identity of the craft which led to government initiatives aimed at creating protection and preservation of craft’s ingenuity owing to the craftsmen and its community through the creation of geographical indication (GI) tag, Craftmark logo and also through handicraft census. With over 200 crafts GI tagged, it is beneficial to the owners as they can safeguard their products from unauthorized commercial use. Presence of the GI tag has still left some room for improvements for craftsman’s awareness and fight for their rights. The Craftmark logo is an initiative to provide a mark for genuine handicraft for the consumers to authenticate their purchase. Private exhibitions and museums purposefully created for documentation and preservation of the handicrafts. Role of design in craft innovation With above systematic study, the working groups further discovered various gaps as an opportunity for design-driven strategic intervention. Practice-based Design research facilitates the application of design strategies at various levels to imagine a craft social innovation and its sustainable future

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Insulin degludec

Insulin analogues have revolutionized the treatment of diabetes mellitus, and the advent of newer insulin analogues have provided better glycemic control with lesser incidence of hypoglycemia. Insulin degludec is a second-generation, ultra-long-acting acylated basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Findings from clinical trials have demonstrated that new-generation, once-daily basal insulin degludec provides similar A1C control as compared to insulin glargine, both administered as basal-oral therapy or in combination with insulin aspart, with the added benefits of lower rates of hypoglycemia, particularly nocturnal hypoglycemia

Assessment of anxiety and behavior changes on digital education in undergraduate dental students during COVID-19 pandemic

Context: Due to the COVID-19 pandemic, to avoid community spread of the disease, various academic institutions were closed to prevent infecting the students. Hence their relocation from the institution resulted in online academic learning. Reports indicated that the students undergoing online academic learning experienced distress in the form of anxiety, anger and insomnia. Aims: The aim of this study was to assess the changes in mental attitude, behavioral pattern, and anxiety level along with the impact of online education on academics so as to receive suggestions regarding digital education from undergraduate dental students. Settings and Design: An observational, cross-sectional study was conducted formulating online semi-structured, open-ended questionnaires, to obtain inputs regarding digital education using Google Forms and the snowball sampling method. Subjects and Methods: The data collection was initiated on August 6 at 4 PM IST and closed on August 13, 2020, at 4 PM IST. We received the response from 488 students from five dental institutions of Karnataka, Maharashtra, and Andhra Pradesh. Statistical analysis was performed using Microsoft Excel for obtaining an overall percentage of mental attitude, anxiety, behavior changes, and academics. IBM SPSS Statistics 20 software was used to evaluate correlation among all parameters with the analysis of variance test. Results: A statistically significant association was seen between digital education with anxiety (P = 0.015), behavior changes (P = 0.000), and academics (P = 0.000). Students contributed positive inputs to enhance the learning outcome in academics on the digital platform. Conclusions: Online academic sessions have eased the learning process to a certain extent, but this mode of education needs more refinement in the form of clinical demonstration videos, sharing of study material, well-planned and spaced definite timetable, and postsession evaluation. These suggestions were put forth by the students as feedback to make the experience entirely stress-free and aid their learning process

Optimization of Pretreatments for Dehydration of Bittergourd

Bittergourd (Momordica charantia L) slices were i) blanched for 3 min in boiling water, ii) blanched for 3 min in 5% salt solution, and iii) dipped in 15% salt solution for 30 min. The samples dehydrated in mechanical tray dryer were found to be more acceptable as compared to sun dried and solar dried products. Exhaustive dehydration trails were conducted using mechanical tray dryer in three replications at 60, 70, 80 and 90°C drying air temperatures. The dried bittergourd slices were packed in different types of containers for predicting their shelf life. Bittergourd slices blanched in boiling water were of the best quality followed by 5% salt solution at drying temperature of 60 and 70°C. The samples blanched in boiling water and dehydrated at 60°C were observed most acceptable in terms of rehydration property and nutritional quality, It also proved to be superior in colour retention up to 60 days of storage. The result showed that the rehydrated bittergourd slices could very well be utilized for substituting the fresh product during offseason