Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX)

<p>Abstract</p> <p>Background</p> <p>The human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes.</p> <p>Results</p> <p>To determine if MRX genes were recruited to the X, or whether their brain-specific functions were acquired after relocation to the mammalian X chromosome, we examined the location and expression of their orthologues in marsupials, which diverged from human approximately 180 million years ago. We isolated and mapped nine tammar wallaby MRX homologues, finding that six were located on the tammar wallaby X (which represents the ancient conserved mammal X) and three on chromosome 5, representing the recently added region of the human X chromosome. The location of MRX genes within the same synteny groups in human and wallaby does not support the hypothesis that genes with an important function in the brain were recruited in multiple independent events from autosomes to the mammalian X chromosome. Most of the tammar wallaby MRX homologues were more widely expressed in tammar wallaby than in human. Only one, the tammar wallaby <it>ARX </it>homologue (located on tammar chromosome 5p), has a restricted expression pattern comparable to its pattern in human. The retention of the brain-specific expression of <it>ARX </it>over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function.</p> <p>Conclusion</p> <p>Our results suggest all the genes in this study may have originally had more general functions that became more specialised and important in brain function during evolution of humans and other placental mammals.</p

Foundation and empire : a critique of Hardt and Negri

In this article, Thompson complements recent critiques of Hardt and Negri's Empire (see Finn Bowring in Capital and Class, no. 83) using the tools of labour process theory to critique the political economy of Empire, and to note its unfortunate similarities to conventional theories of the knowledge economy

Use of a radiopaque localizer grid to reduce radiation exposure

Abstract Background Minimally invasive spine surgery requires placement of the skin incision at an ideal location in the patient's back by the surgeon. However, numerous fluoroscopic x-ray images are sometimes required to find the site of entry, thereby exposing patients and Operating Room personnel to additional radiation. To minimize this exposure, a radiopaque localizer grid was devised to increase planning efficiency and reduce radiation exposure. Results The radiopaque localizer grid was utilized to plan the point of entry for minimally invasive spine surgery. Use of the grid allowed the surgeon to accurately pinpoint the ideal entry point for the procedure with just one or two fluoroscopic X-ray images. Conclusions The reusable localizer grid is a simple and practical device that may be utilized to more efficiently plan an entry site on the skin, thus reducing radiation exposure. This device or a modified version may be utilized for any procedure involving the spine

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy

Objective: This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals. Methods: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two weeks of continuous video-EEG and simultaneous ECG recordings were acquired for two weeks from 11 weeks post-KA SE. The video-EEG recordings were analyzed blindly to quantify the number and severity of spontaneous seizures, and the ECG recordings analyzed for measures of heart rate variability (HRV). PicroSirius red histology was performed to assess cardiac fibrosis, and intracellular Ca2+ levels and cell contractility were measured by microfluorimetry. Results: All 9 post-KA SE rats were demonstrated to have spontaneous recurrent seizures on the two-week video-EEG recording acquired from 11 weeks SE (seizure frequency ranging from 0.3 to 10.6 seizures/day with the seizure durations from 11 to 62 s), and none of the 8 control rats. Left ventricular wall thickness was thinner, left ventricular internal dimension was shorter, and ejection fraction was significantly decreased in chronically epileptic rats, and was negatively correlated to seizure frequency in individual rats. Diastolic dysfunction was evident in chronically epileptic rats by a decrease in mitral valve deceleration time and an increase in E/E` ratio. Measures of HRV were reduced in the chronically epileptic rats, indicating abnormalities of cardiac autonomic function. Cardiac fibrosis was significantly increased in epileptic rats, positively correlated to seizure frequency, and negatively correlated to ejection fraction. The cardiac fibrosis was not a consequence of direct effect of KA toxicity, as it was not seen in the 6/10 rats from separate cohort that received similar doses of KA but did not go into SE. Cardiomyocyte length, width, volume, and rate of cell lengthening and shortening were significantly reduced in epileptic rats. Significance: The results from this study demonstrate that chronic epilepsy in the post-KA SE rat model of TLE is associated with a progressive deterioration in cardiac structure and function, with a restrictive cardiomyopathy associated with myocardial fibrosis. Positive correlations between seizure frequency and the severity of the cardiac changes were identified. These results provide new insights into the pathophysiology of cardiac disease in chronic epilepsy, and may have relevance for the heterogeneous mechanisms that place these people at risk of sudden unexplained death

Surgery alone for papillary thyroid microcarcinoma is less costly and more effective than long term active surveillance

Background: Papillary thyroid microcarcinoma is a subtype of thyroid cancer that may be managed with active surveillance rather than immediate surgery. Active surveillance decreases complication rates and may decrease health care costs. This study aims to analyze complication rates of thyroid surgery, papillary thyroid microcarcinoma recurrence, and survival rates. Additionally, the costs of surgery versus hypothetic active surveillance for papillary thyroid microcarcinoma are compared in an Australian cohort. Methods: Papillary thyroid microcarcinoma patients were included from a prospectively collected surgical cohort of patients treated for papillary thyroid cancer between 1985 and 2017. The primary outcomes were the complications of thyroid surgery, recurrence-free survival, overall survival, and cost of surgical treatment and active surveillance. Results: In a total of 349 patients with papillary microcarcinoma with a median age of 48 years (range, 18–90 years), the permanent operative complications rate was 3.7%. Postoperative radioactive iodine did not decrease recurrence-free survival (P = .3). The total cost of surgical treatment was $10,226 Australian dollars, whereas hypothetic active surveillance was at a yearly cost of$756 Australian dollars. Estimated cost of surgical papillary thyroid microcarcinoma treatment was equivalent to the cost of 16.2 years of active surveillance. Conclusion: Surgery may have a long-term economic advantage for younger Australian patients with papillary thyroid microcarcinoma who are likely to require more than 16.2 years of follow-up in an active surveillance scheme

Socioeconomic profile of diabetic patients with and without foot problems

Introduction: To identify the differences in a socioeconomic profile between two cohorts of diabetic patients &#x2013; one with diabetic foot problems and another without diabetic foot problems. Materials and methods: The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1C) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis. Results: With multivariate analysis, Malay ethnicity (p&#60;0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD &#x0024;2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1C level (&#x003E;7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without. Conclusions: There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without

Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients

Disparate Functional Responses to β-adrenergic and Ischaemic Challenge in Male and Female Hypertrophic Cardiomyocytes

Cardiac hypertrophy is the most potent cardiovascular risk factor after age, with relative mortality risk greater in women. The cognate issue of whether ischaemia coincident with hypertrophic co-morbidity has differing gender aetiology/outcome has not been addressed. We used a novel polygenic model of hypertrophy to examine male/female cellular stress responses in normal and hypertrophic cardiomyocytes.Centro de Investigaciones Cardiovasculare