Key Genes in Prostate Cancer Progression: Role of MDM2, PTEN, and TMPRSS2-ERG Fusions

In recent years, multiple genes or their protein products have been linked to initiation and progression of prostate cancer. Such genes include TMPRSS2, ERG, PTEN, and MDM2. This chapter discusses the pathological roles as well as the potential diagnostic and therapeutic applications of these genes that are highly expressed in prostate cancer when compared to other cancer types. The presence of these genes and related defects are linked to growth, progression, metastasis, invasiveness and resistance in prostate cancers. While knowledge related to TMPRSS2, ERG, and PTEN have been accumulating in the last two decades, the prometastatic role of MDM2 has been emerging in the last few years and revealing important functions related to prostate cancer progression

Birdland

Ope

Molecular Modulation of Osteoblasts and Osteoclasts in Type 2 Diabetes

Diabetes is a common disease affecting majority of populations worldwide. Since 1980, there has been an increase in the number of people diagnosed as prediabetic and diabetic. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, stroke, and myocardial infarction. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization mainly due to increased adiposity among diabetic patients that affects both osteoblast and osteoclast functions. Other factors that increase fracture risk in diabetic patients are increased oxidative stress, inflammation, and drugs administered to diabetic patients. This review reports the modulation of different pathways that affect bone metabolism in diabetic conditions

Ascension

Ope

Molecular Modulation of Osteoblasts and Osteoclasts in Type 2 Diabetes

Diabetes is a common disease affecting majority of populations worldwide. Since 1980, there has been an increase in the number of people diagnosed as prediabetic and diabetic. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, stroke, and myocardial infarction. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization mainly due to increased adiposity among diabetic patients that affects both osteoblast and osteoclast functions. Other factors that increase fracture risk in diabetic patients are increased oxidative stress, inflammation, and drugs administered to diabetic patients. This review reports the modulation of different pathways that affect bone metabolism in diabetic conditions

GABAergic Inhibition Controls Receptive Field Size, Sensitivity, and Contrast Preference of Direction Selective Retinal Ganglion Cells Near the Threshold of Vision

Information about motion is encoded by direction-selective retinal ganglion cells (DSGCs). These cells reliably transmit this information across a broad range of light levels, spanning moonlight to sunlight. Previous work indicates that adaptation to low light levels causes heterogeneous changes to the direction tuning of ON-OFF (oo)DSGCs and suggests that superior-preferring ON-OFF DSGCs (s-DSGCs) are biased toward detecting stimuli rather than precisely signaling direction. Using a large-scale multielectrode array, we measured the absolute sensitivity of ooDSGCs and found that s-DSGCs are 10-fold more sensitive to dim flashes of light than other ooDSGCs. We measured their receptive field (RF) sizes and found that s-DSGCs also have larger receptive fields than other ooDSGCs; however, the size difference does not fully explain the sensitivity difference. Using a conditional knock-out of gap junctions and pharmacological manipulations, we demonstrate that GABA-mediated inhibition contributes to the difference in absolute sensitivity and receptive field size at low light levels, while the connexin36-mediated gap junction coupling plays a minor role. We further show that under scotopic conditions, ooDSGCs exhibit only an ON response, but pharmacologically removing GABA-mediated inhibition unmasks an OFF response. These results reveal that GABAergic inhibition controls and differentially modulates the responses of ooDSGCs under scotopic conditions

The re-emerging association between tuberculosis and diabetes: lessons from past centuries

The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we evaluate unique aspects of this comorbidity in older times, such as the frequent diabetic comas that suggest challenges for proper DM management as insulin was being implemented, or the absence of antibiotics to cure TB. Despite the unique aspects of each study period, the literature across times is consistent in key aspects of the association. Namely, a higher TB prevalence among DM (versus non-DM patients), the importance of glucose control and chronic DM on TB susceptibility and the higher risk of death among patients with the comorbidity. From the older literature, we can infer the likely contribution of type 1 DM to TB (in addition to type 2), regardless of their differing autoimmune or metabolic pathophysiology, respectively. Furthermore, in the older literature there was a notable reporting of DM development among TB patients, even though DM usually preceded TB. This observation deserves further epidemiological and basic studies to elucidate this intriguing aspect of the relationship between TB and DM

CLINICAL PROFILE OF ADOLESCENT GIRLS WITH GYNAECOLOGICAL PROBLEMS IN RURAL SOUTH INDIA

Objective: The purpose of the six months observational study is to evaluate the gynaecological problems of the adolescent girls, attending the gynaecological outpatient department of a secondary care referral healthcare facility in rural south India. Methods: After ethical clearance, adolescent girls in the age group of 10-19 y having gynaecological problems, who had experienced at least 3 consecutive menstrual cycles, and who showed willingness towards study were included; and adolescent girls in 10-19 y age group having a pregnancy and its complications were excluded. Results: Out of 161 adolescent girls, 46.01% belong to late adolescence with more distribution of gynaecological problems. The gynaecological problems majorly observed were menstrual disorder 59.63%, abdominal pain (11.18%), white discharge per vagina (9.94%), and 8.07% of heavy menstrual bleeding. The menstrual disorder complained with amenorrhea 40.63%, polymenorrhea 18.75%, and menorrhagia 16.67%. In our study, 26.09% and 32.3% of adolescent girls were anaemic and underweight, respectively. Conclusion: In conclusion, our study showcased evidently that young adolescent girls are at higher risk of both gynaecological problems and menses disorders in the rural setting; for whom more amount of awareness to be parented and education of menstrual hygiene and hemodynamic effects has to be culminated through health education, for a future healthier nation