Tumor suppression by cell competition through regulation of the Hippo pathway

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib(-) cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does not explain how scrib(-) cells are prevented from overproliferating. We report that cell competition between scrib(-) and wild-type cells prevents hyperproliferation by suppressing Yki activity in scrib(-) cells. Suppressing Yki activation is critical for scrib(-) clone elimination by cell competition, and experimental elevation of Yki activity in scrib(-) cells is sufficient to fuel their neoplastic growth. Thus, cell competition acts as a tumor-suppressing mechanism by regulating the Hippo pathway in scrib(-) cells.     

Posterior Scrotal Artery Flap to Cover a Groin Defect: A New Technique

Commonly, a groin defect is reconstructed with flaps from ipsilateral thigh or lower abdomen. Here we present a case report of use of a pedicled flap from the posterior scrotum based on posterior scrotal artery to cover a groin defect exposing femoral vessels. Posterior scrotal artery, to best of our knowledge, has not been described in the literature to cover a groin defect.     

Primary sleep disorders seen at a Neurology service-based sleep clinic in India: Patterns over an 8-year period

There is an increasing awareness for recognition of sleep disorders in India; however, there is still a huge gap in the number of people suffering from various sleep disorders, in the community versus those visiting hospital clinics for the same. Ours is a neurology services-based sleep disorders clinic, which has evolved successfully over the last decade. In this study, we aimed to evaluate the changes in referral patterns and distribution of various sleep disorders in the patients presenting to the clinic.

Materials and Methods:

This is a retrospective chart review-based study on all patients seen over an 8-year period, divided into 2 groups comprising of patients seen during the first 4 years versus those seen over the next 4 years. Only those patients who had the sleep disorder as their presenting manifestation and those who had been formally interviewed with a pre-structured questionnaire detailing about the main features of the common sleep disorders according to the ICSD-R were included. Patients, in whom the sleep disorder could be clearly attributable to another neurological or systemic disorder, were excluded. Statistical analysis was carried out to identify the differences between the two groups as regards the distribution of various sleep disorders and other clinical data.

Results:

Among 710 patients registered in the clinic, 469 were included for analysis and 222 patients formed group 1 while 247 formed group 2. The main differences observed were in the form of a clear increase in the percentage of patients with sleep-related breathing disorders, sleep-related movement disorder, and the hypersomnias on comparison of distribution over the first 4 years versus the last 4 years; while a clear decline was seen in the number of patients with insomnia and parasomnias. A 3-fold increase was observed in the number of patients in whom polysomnography was obtained.

Conclusion:

The distribution of various sleep disorders as seen in a neurology service-based sleep clinic is demonstrated in this study. Increasing referrals for sleep-disordered breathing, restless legs syndrome, and fewer referrals for insomnia and parasomnias might reflect on changing physician and patient awareness in our community.     

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.     

Markedly disturbed sleep in medically refractory compared to controlled epilepsy - a clinical and polysomnography study

PurposeTo evaluate sleep disturbances or sleep related events and their characteristics among patients with medically refractory epilepsy, compared to those with controlled epilepsy.MethodsIn a prospective case-controlled study, patients of medically refractory and controlled epilepsy were recruited and history pertaining to epilepsy and sleep related events and Epworth sleepiness scores were recorded and all patients underwent over night polysomnography.ResultsAmong 40 patients, 20 with medically refractory (Group 1) and 20 with controlled epilepsy (Group 2) (median age 18, range 10–35 years), the self reported sleep parameters in Group 1 patients were found to be significantly different as compared to Group 2, in terms of the duration of night time sleep, day time sleep, day time nap frequency, total sleep hours per day, excessive daytime sleepiness (EDS)(45% vs. 15%) and average sleep hours over the week prior to polysomnography. On PSG, Group 1 patients showed significantly less total sleep time [340.4 min (147–673) vs. 450.3 min (330–570)] with delayed sleep latency and REM latency, poor sleep efficiency [80.45 (40.5–98.0) vs. 95.45 (88.4–99.7)] and frequent arousals and wake after sleep onset (WASO) compared to Group 2 patients. Four patients (20%) in Group 1 compared to none in Group 2 were found to have mild obstructive sleep apnea.ConclusionsOur results indicate that medically refractory epilepsy patients believe that they spend more time sleeping, in contrast to the documented shorter sleep duration on polysomnography. This difference between perceived and actual sleep seems, by their data, to arise mainly from sleep fragmentation, disturbed architecture and the interesting finding of associated sleep apnea among the medically refractory epilepsy patients.