Can noise reduction filters improve low-radiation-dose chest CT images? Pilot study

Effect of noise reduction filters on chest computed tomographic (CT) images acquired with 50% radiation dose reduction was evaluated. Two sets of images were acquired with multi-detector row CT at standard (220-280 mA) and 50% reduced (110-140 mA) tube current at the level of the carina. After postprocessing with six noise reduction filters, images were compared with baseline standard-dose images for noise, sharpness, and contrast in lungs, mediastinum, and chest wall. Quantitative image noise was measured in descending thoracic aorta. Modulation transfer functions were calculated from CT images of 50-microm wire. Noise reduction filters reduced image noise on low-radiation-dose chest CT images, with some compromise in image sharpness and contrast assessed qualitatively, and slightly altered modulation transfer function at higher spatial frequencies.     

Regulation of c-Raf-1: therapeutic implications

The mitogen activated protein kinase (MAPK) or Ras/Raf/MAPK kinase (MEK)/ERK signaling cascade is a ubiquitously expressed intracellular signaling pathway that transmits mitogenic stimuli to the nucleus through a series of sequential phosphorylation events and controls such cellular functions as proliferation, differentiation, and apoptosis. Components of this pathway such as ras and raf are oncogenes and as such aberrancy in their encoded proteins results in malignant transformation. The MAPK pathway is dysregulated in approximately 30% of all human tumors and therefore targeting specific components of this pathway that regulate pleiotropic cellular processes using such strategies as isoprenylation inhibitors, antisense oligodeoxyribonucleotides, and inhibitors of the kinase function represent attractive therapeutic options. raf kinase, a downstream effector of ras, has been known to be functionally aberrant in various human tumors. The 3 isoforms of raf have been studied extensively, and agents targeting c-raf are presently undergoing early-phase clinical testing. The outcomes of these trials have wide-ranging clinical implications in the management of cancers. This review addresses the rationale for targeting raf, the diverse cellular functions regulated by c-raf, and the current status of various pharmacological approaches targeting c-raf.     

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.     

Introduction of new vaccines in state immunization schedule — Delhi’s experience

Immunization is an established, cost-effective, preventive intervention to improve child survival. To provide protection against vaccine preventable diseases, all countries in the world have an immunization program that offers selected vaccines to the eligible beneficiaries. In India, Expanded Program of Immunization was started in 1978, and then Universal Immunization Program was launched in 1985 with six antigens. This article describes the experience with institutionalization of four state-specific vaccines by Delhi in its immunization schedule to enlarge the ambit of immunization services. It attempts to highlight the state’s perspective in terms of the implementation policy, operational strategy adopted and evolution of immunization program in the state over 16 years.     

Next-Generation Sequencing Based Approach to Identify Underlying Genetic Defects of Glanzmann Thrombasthenia

Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the ITGA2B/ITGB3 genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using in-silico prediction tools. The variants include three missense (3/7 = 43%) (ITGA2B:c.1028 T > C, ITGA2B:c.1186G > A, ITGB3:c.1388G > C), two deletions (ITGA2B:c.559delG, ITGA2B:c.3092delT), one duplication (ITGA2B:c.1424_1427dupAGGT) and nonsense variant (ITGA2B:c.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.     

The Role of Microbial Biofilms in Osteonecrosis of the Jaw Associated with Bisphosphonate Therapy

Microbial biofilms have been observed and described in bone specimens of patients with bisphosphonate (BP)-associated osteonecrosis of the jaw (BONJ) and investigators are more recently suggesting that this condition essentially represents an osteomyelitis of the jaw clinically, with greater susceptibility in some patients on BP therapy. This article explains the role of microbial biofilms in BONJ and also discusses associated factors in the disease pathogenesis, which include BP effects on bone remodeling, anti-angiogenesis, matrix necrosis, microcracks, soft tissue toxicity, and inflammation and wound healing. Recent findings suggest a key role for microbial biofilms in the pathogenesis of BONJ; this has important therapeutic implications because biofilm organisms represent a clinical target for prevention and treatment efforts aimed at reducing the significant morbidity and costs associated with this condition.     

Benign cystic teratoma of ovary perforating into small intestine with co-existent typhoid fever.

Intra-peritoneal rupture or perforation into adjacent abdominal viscera is a rare complication of benign cystic teratoma (dermoid cyst) of the ovary. We report a 48-year-old woman in whom an ovarian dermoid cyst perforated into a loop of the small bowel. The patient had co-existing typhoid fever, which probably predisposed to this complication. She recovered on antibiotic therapy and after surgical excision.