Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.     

Visual outcome after fireworks injuries

BACKGROUND: The epidemiology and prognosis of fireworks-related injuries treated at a tertiary eye care center in less developed nations remain unknown. METHODS: We conducted a prospective observational study that enrolled all consecutive eyes with fireworks-related ocular injury visiting our trauma clinic during a 1-year period. Eyes were graded by ocular trauma classification and followed for 6 months at least. Best corrected visual acuity (BCVA) at 6 months was considered the final visual outcome. Data were analyzed. RESULTS: Twenty-five (96%) of a total of 26 patients enrolled during study period were male patients and 13 (50%) were younger than 15 years. The type of fireworks involved was a bottle rocket in 38.5%. Factors significantly associated with better final visual outcome were better BCVA at presentation (p = 0.041), absence of bottle rocket injury (p = 0.028), closed globe injury (p = 0.028), absence of relative afferent pupillary defect (p = 0.019), absence of intraocular foreign body (p = 0.026), and absence of endophthalmitis (p = 0.006). Besides poor visual outcome, bottle rocket injuries were more frequently associated with facial lacerations, intraocular foreign body, and endophthalmitis development. CONCLUSION: Fireworks-related ocular injuries commonly affect young male subjects of northern India. Visual outcome is better in eyes having better initial BCVA or closed globe injury and if relative afferent pupillary defect, bottle rocket injury, intraocular foreign body, and endophthalmitis are absent.     

Association of symptoms and breast cancer in population‐based mammography screening in Finland

The study purpose was to assess association of symptoms at screening visits with detection of breast cancer among women aged 50–69 years during the period 2006–2010. Altogether 1.2 million screening visits were made and symptoms (lump, retraction, secretion etc.) were reported either by women or radiographer. Breast cancer risk was calculated for each symptom separately using logistic regression [odds ratio (OR)] and 95% confidence intervals (CIs). Of the 1,198,410 screening visits symptoms were reported in 298,220 (25%) visits. Breast cancer detection rate for women with and without symptoms was 7.8 per 1,000 and 4.7 per 1,000 screening visits, respectively, whereas lump detected 32 cancers per 1,000 screens. Women with lump or retraction had an increased risk of breast cancer, OR = 6.47, 95% CI 5.89?7.09 and OR = 2.19, 95% CI 1.92–2.49, respectively. The sensitivity of symptoms in detecting breast carcinoma was 35.5% overall. Individual symptoms sensitivity and specificity ranged from, 0.66 to 14.8% and 87.4 to 99.7%, respectively. Of 5,541 invasive breast cancers, 1,993 (36%) reported symptoms at screen. Breast cancer risk among women with lump or retraction was higher in large size tumors (OR = 9.20, 95% CI 8.08–10.5) with poorly differentiated grades (OR = 5.91, 95% CI 5.03–6.94) and regional lymph nodes involvement (OR = 6.47, 95% CI 5.67–7.38). This study was done in a setting where breast tumors size is generally small, and symptoms sensitivity and specificity in diagnosing breast tumors were limited. Importance of breast cancer symptoms in the cancer prevention and control strategy needs to be evaluated also in other settings.     

Eltrombopag therapy in newly diagnosed steroid non-responsive ITP patients

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterised by isolated thrombocytopenia (peripheral blood platelet count <100 × 10⁹/L) in the absence of other causes or disorders that may be associated with thrombocytopenia. The upfront treatment in newly diagnosed ITP patients is steroids; however, about one-third patients do not respond, and require other treatment, including IVIg, anti-D, or splenectomy. Previous studies have shown decreased platelet production in some ITP patients, aside from the evidence of enhanced platelet destruction. Thrombopoietin receptor agonists (TPO-RA), such as eltrombopag have been shown to provide good response in steroid non-responsive chronic ITP patients. We have studied response to eltrombopag in 25 newly diagnosed steroid non-responsive ITP patients; 80 % patients showed response at the end of 1 month, and 76 % sustained response at the end of 3 months. The platelet count rose from a mean value of 17.5 ± 3.6–152.5 ± 107.9 × 10⁹/L at the end of 1 month. Our results suggest a possible role of eltrombopag in newly diagnosed steroid non-responsive ITP patients. However, our study is limited in that it is a single-centre study, with a small sample size, and lacks a long-term safety profile. Our findings highlight the potential value of a larger prospective study on the upfront use of TPO-RA in patients of ITP.     

Human DNA Ligases: A Comprehensive New Look for Cancer Therapy

Living organisms belonging to all three domains of life, viz., eubacteria, archaeabacteria, and eukaryotes encode one or more DNA ligases. DNA ligases are indispensable in various DNA repair and replication processes and a deficiency or an inhibition of their activity can lead to accumulation of DNA damage and strand breaks. DNA damage, specially strand breaks at unsustainable levels can lead to replication block and/or cell death. DNA ligases as potential anticancer targets have been realized only recently. There is enough rationale to suggest that ligases have a tremendous potential for novel therapeutics including anticancer and antibacterial therapy, specially when the world is facing acute problems of drug resistance and chemotherapy failure, with an immediate need for new therapeutic targets. Here, we review the current state of the art in the development of human ligase inhibitors, their structures, molecular mechanisms, physiological effects, and their potential in future cancer therapy. Citing examples, we focus on strategies for improving the activity and specificity of existing and novel inhibitors by using structure‐based rational approaches. In the end, we describe potential new sites on the ligase I protein that can be targeted for the development of novel inhibitors. This is the first comprehensive review to compile all known human ligase inhibitors and to provide a rationale for the further development of ligase inhibitors for cancer therapy.     

Iris intraocular foreign bodies: safe and successful removal through limbus

Metallic iris intra ocular foreign body (IOFBs) with minimal ocular damage pose an interventional challenge. We report safe removal of metallic intraocular foreign bodies embedded on the iris, in three cases by use of intraocular magnets. Two eyes had a clear lens with best corrected visual acuity (BCVA) of 20/20, while the third eye had a BCVA of 20/200 with siderotic cataract. Ultrasound biomicroscopy confirmed the superficial impaction of IOFB into the iris. Foreign bodies were successfully removed via the limbal route with a 20 g intravitreal magnet atraumatically in all 3 cases with preservation of their pre-operative BCVA. Case series highlights the usefulness and safety of intraocular magnet for removal of metallic iris foreign bodies in selected cases. Prior ultrasound biomicroscopy to know the actual depth of penetration of IOFB into the iris and preoperative confirmation of magnetic property of IOFB are essential.     

Nanocarriers: promising vehicle for bioactive drugs

Development of new delivery systems that deliver the potential drug specifically to the target site in order to meet the therapeutic needs of the patients at the required time and level remains the key challenge in the field of pharmaceutical biotechnology. Developments in this context to achieve desired goal has led to the evolution of the multidisciplinary field nanobiotechnology which involves the combination of two most promising technologies of 21st century--biotechnology and nanotechnology. Nanobiotechnology encompasses a wide array of different techniques to improve the delivery of biotech drugs, and nanoparticles offer the most suitable form whose properties can be tailored by chemical methods. This review highlights the different types of nanoparticulate delivery systems employed for biotech drugs in the field of molecular medicine with a short overlook at its applications and the probable associated drawbacks.