Recombinant erythropoietin is neuroprotective in a novel mouse oxidative injury model

To identify neuroprotective changes in gene expression, we developed a neonatal mouse model of moderate to severe oxidative brain injury and hypothesized that recombinant erythropoietin (rEpo) would decrease the expression of proapoptotic and proinflammatory genes 24 and 48 h, respectively, after injury and increase the expression of neurogenic and angiogenic genes 168 h after injury. Postnatal day 10 BALB-c mice underwent sham surgery or right common carotid artery occlusion followed by alternating hypoxia and hyperoxia and were then treated with rEpo (5,000 U/kg s.c.) or saline (vehicle) daily for up to three doses. At death, gross brain injury was assessed, then hippocampus, cortex, and thalamus were isolated for RNA or protein extraction. Microarray analysis, real-time polymerase chain reaction, and Bio-Plex suspension array system validation were performed. rEpo decreased both incidence and severity of brain injury (median injury score 3 vs. 0, p < 0.0001) and reduced the injury-induced increases in interleukin-1alpha and interleukin-6 gene expression (p < 0.001), with corresponding effects on protein translation. Similarly, the expression of caspase-1, caspase-4, and caspase-6 and of p53 was increased by brain injury at 24 h, but mitigated by rEpo (p < 0.01). The interleukin-10 expression was higher in the rEpo-treated animals. Apoptotic and proinflammatory gene expression persisted for 168 h. There was no increase in angiogenic gene expression at the time points studied.     

Enhanced phytoremediation of volatile environmental pollutants with transgenic trees

Small, volatile hydrocarbons, including trichloroethylene, vinyl chloride, carbon tetrachloride, benzene, and chloroform, are common environmental pollutants that pose serious health effects. We have developed transgenic poplar (Populus tremula x Populus alba) plants with greatly increased rates of metabolism and removal of these pollutants through the overexpression of cytochrome P450 2E1, a key enzyme in the metabolism of a variety of halogenated compounds. The transgenic poplar plants exhibited increased removal rates of these pollutants from hydroponic solution. When the plants were exposed to gaseous trichloroethylene, chloroform, and benzene, they also demonstrated superior removal of the pollutants from the air. In view of their large size and extensive root systems, these transgenic poplars may provide the means to effectively remediate sites contaminated with a variety of pollutants at much faster rates and at lower costs than can be achieved with current conventional techniques.     

A gene from the cellulose synthase-like C family encodes a beta-1,4 glucan synthase

Despite the central role of xyloglucan (XyG) in plant cell wall structure and function, important details of its biosynthesis are not understood. To identify the gene(s) responsible for synthesizing the beta-1,4 glucan backbone of XyG, we exploited a property of nasturtium (Tropaeolum majus) seed development. During the last stages of nasturtium seed maturation, a large amount of XyG is deposited as a reserve polysaccharide. A cDNA library was produced from mRNA isolated during the deposition of XyG, and partial sequences of 10,000 cDNA clones were determined. A single member of the C subfamily from the large family of cellulose synthase-like (CSL) genes was found to be overrepresented in the cDNA library. Heterologous expression of this gene in the yeast Pichia pastoris resulted in the production of a beta-1,4 glucan, confirming that the CSLC protein has glucan synthase activity. The Arabidopsis CSLC4 gene, which is the gene with the highest sequence similarity to the nasturtium CSL gene, is coordinately expressed with other genes involved in XyG biosynthesis. These and other observations provide a compelling case that the CSLC gene family encode proteins that synthesize the XyG backbone.     

Identification of Cardiometabolic Risk Among Collegiate Football Players

Context:

Excessive fat mass clearly has adverse effects on metabolic processes that can ultimately lead to the development of chronic disease. Early identification of high-risk status may facilitate referral for definitive diagnostic tests and implementation of interventions to reduce cardiometabolic risk.

Objective:

To document the prevalence of metabolic syndrome among collegiate football players and to develop a clinical prediction rule that does not require blood analysis to identify players who may possess a high level of cardiometabolic risk.

Design:

Cross-sectional cohort study.

Setting:

University athletic training research laboratory.

Patients or Other Participants:

Sixty-two National Collegiate Athletic Association Division I Football Championship Subdivision football players (age  =  19.9 ± 1.2 years, height  =  182.6 ± 6.1 cm, mass  =  97.4 ± 18.3 kg).

Main Outcome Measure(s):

Anthropometric characteristics associated with body fat, isokinetic quadriceps strength, and biometric indicators associated with metabolic syndrome were measured. Participants were classified as high risk or low risk for future development of type 2 diabetes and cardiovascular disease.

Results:

The prevalence of metabolic syndrome in the cohort was 19% (12 of 62), and 79% (49 of 62) of the players exceeded the threshold for 1 or more of its 5 components. A 4-factor clinical prediction rule that classified individuals on the basis of waist circumference, blood pressure, quadriceps strength, and ethnic category had 92% sensitivity (95% confidence interval  =  65%, 99%) and 76% specificity (95% confidence interval  =  63%, 86%) for discrimination of high-risk or low-risk status.

Conclusions:

The risk for developing type 2 diabetes and cardiovascular disease appears to be exceptionally high among collegiate football players. A lack of race-specific criteria for the diagnosis of metabolic syndrome almost certainly contributes to an underestimation of the true level of cardiometabolic risk for African American collegiate football players.     

Differential expression of respiratory long-term facilitation among inbred rat strains

We tested the hypotheses that: (1) long-term facilitation (LTF) following acute intermittent hypoxia (AIH) varies among three inbred rat strains: Fischer 344 (F344), Brown Norway (BN) and Lewis rats and (2) ventral cervical spinal levels of genes important for phrenic LTF (pLTF) vary in association with pLTF magnitude. Lewis and F344, but not BN rats exhibited significant increases in phrenic and hypoglossal burst amplitude 60 min post-AIH that were significantly greater than control experiments without AIH, indicating strain differences in phrenic (98%, 56% and 20%, respectively) and hypoglossal LTF (66%, 77% and 5%, respectively). Ventral spinal 5-HT_2A receptor mRNA and protein levels were higher in F344 and Lewis versus BN, suggesting that higher 5-HT_2A receptor levels are associated with greater pLTF. More complex relationships were found for 5-HT₇, BDNF and TrkB mRNA. BN had higher 5-HT₇ and TrkB mRNA versus F344; BN and Lewis had higher BDNF mRNA levels versus F344. Genetic variations in serotonergic function may underlie strain differences in AIH-induced pLTF.     

Widening the lens on standardized patient assessment: what the encounter can reveal about the development of clinical competence.

The standardized patient (SP) examination is used in a majority of medical schools to test clinical skills. This examination usually yields both numerical ratings of clinical skill and narrative comments by patients or observers, yet most empirical studies of SP assessment focus on the numerical ratings only. This quantitative focus can lead to a narrow conceptualization of the nature and development of clinical competence. The authors suggest that in addition to utilizing SP numerical ratings, medical educators also use the rich qualitative material produced in the SP examination (e.g., patient comments, videotapes of the examination) to explore students' development of clinical competence, which involves the purposive integration of basic science, technical skill, empathy, communication, professional role, and personal history.     

Getting the blues at a rock concert: A case of severe methaemoglobinaemia

Methaemoglobin is the form of haemoglobin in which the iron moiety of the haem group has been oxidized from the ferrous to the ferric state. Methaemoglobinaemia is due to either an increase in the production of the oxidized haem moiety or due to decreased conversion back to the reduced form. This article presents a case of amyl nitrite‐induced methaemoglobinaemia and discusses the diagnosis and treatment of this disorder.     

Transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type 11

Background: Tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life‐threatening if treatment is delayed. Dermatologists may be the first to encounter such neoplasms. Observations: We report a case of a 53‐year‐old Caucasian woman who presented with a seven‐year history of an asymptomatic, subcutaneous nodule near her right medial canthus. Histology of the lesion revealed transitional epithelium in a papillary growth pattern with numerous goblet cells, scattered mitoses and focal full‐thickness atypia. The patient was diagnosed with transitional cell neoplasm (inverted papilloma‐type) of the nasolacrimal duct. PCR evaluation identified HPV type 11 in the lesion. Conclusion: Our report is one of a growing number of case reports and series detecting HPV DNA in these tumors which further supports HPV as an etiologic agent in epithelial lacrimal sac tumors. We believe that dermatopathologists need to be aware of this entity, as dermatologists may be the first to encounter these neoplasms. Limitations: The association of HPV with this tumor does not prove causality. Vickers JL, Matherne RJ, Allison AW, Wilkerson MG, Tyring SK, Bartlett BL, Rady PL, Kelly BC. Transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type.     

Effective components of treatment for the chemically dependent physician

Physicians with substance use disorders have been documented throughout history. In 1973 the American Medical Association (AMA) acknowledged that physicians suffered from addiction with a landmark policy paper and subsequent Physician Health Conference. Since that time extensive information has been collected regarding the evaluation and treatment of physicians who have the disease of addiction. It is estimated that addiction affects ten percent of the current physician population. Effective treatment for these individuals centers around the fact that addiction is a chronic disease. Treatment initially requires intensive care for stabilization, education, and denial reduction. Ongoing treatment is then needed to help solidify gains made in primary treatment, modify self-care behaviors and attitudes, and to hopefully prevent relapse.