Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavour enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterised by neuronal loss and neuroendocrine abnormalities. However, the brainstem effects of neonatal MSG exposure have not been investigated. It is therefore hypothesized that MSG exposure during the early postnatal period would impact brainstem lower motor neurons involved in feeding behaviour. The effect of neonatal MSG exposure on brainstem lower motor neurons was investigated by exposing rat pups to either 4 mg/g MSG or saline from postnatal day (P) 4 through 10. On P28, brains were preserved by vascular perfusion with fixative, frozen sectioned and stained for Nïssl substance. The number, size and shape of brainstem motor neurons were compared between MSG and saline-exposed animals. MSG exposure had no impact on the total number of neurons in the nuclei examined. However, MSG exposure was associated with a significant increase in the number of round somata in both the trigeminal and facial nuclei. Furthermore, MSG exposure resulted in significantly smaller neurons in all motor nuclei examined. These results suggest that neonatal exposure to MSG impacts the development of brainstem lower motor neurons which may impact feeding and swallowing behaviours in young animals.

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

Distinct effects of rectum delineation methods in 3D-confromal vs. IMRT treatment planning of prostate cancer

BACKGROUND: The dose distribution to the rectum, delineated as solid organ, rectal wall and rectal surface, in 3D conformal (3D-CRT) and intensity-modulated radiotherapy treatment (IMRT) planning for localized prostate cancer was evaluated. MATERIALS AND METHODS: In a retrospective planning study 3-field, 4-field and IMRT treatment plans were analyzed for ten patients with localized prostate cancer. The dose to the rectum was evaluated based on dose-volume histograms of 1) the entire rectal volume (DVH) 2) manually delineated rectal wall (DWH) 3) rectal wall with 3 mm wall thickness (DWH(3)) 4) and the rectal surface (DSH). The influence of the rectal filling and of the seminal vesicles' anatomy on these dose parameters was investigated. A literature review of the dose-volume relationship for late rectal toxicity was conducted. RESULTS: In 3D-CRT (3-field and 4-field) the dose parameters differed most in the mid-dose region: the DWH showed significantly lower doses to the rectum (8.7% ± 4.2%) compared to the DWH(3 )and the DSH. In IMRT the differences between dose parameters were larger in comparison with 3D-CRT. Differences were statistically significant between DVH and all other dose parameters and between DWH and DSH. Mean doses were increased by 23.6% ± 8.7% in the DSH compared to the DVH in the mid-dose region. Furthermore, both the rectal filling and the anatomy of the seminal vesicles influenced the relationship between the dose parameters: a significant correlation of the difference between DVH and DWH and the rectal volume was seen in IMRT treatment. DISCUSSION: The method of delineating the rectum significantly influenced the dose representation in the dose-volume histogram. This effect was pronounced in IMRT treatment planning compared to 3D-CRT. For integration of dose-volume parameters from the literature into clinical practice these results have to be considered

Reproducibility of patient setup by surface image registration system in conformal radiotherapy of prostate cancer

<p>Abstract</p> <p>Background</p> <p>The reproducibility of patient setup for radiotherapy is based on various methods including external markers, X-rays with planar or computerized image acquisition, and, more recently, surface matching imaging. We analyzed the setup reproducibility of 16 patients affected by prostate cancer who underwent conformal radiotherapy with curative intent by using a surface image registration system.</p> <p>Methods</p> <p>We analyzed the setup reproducibility of 16 patients affected by prostate cancer candidates for conformal radiotherapy by using a surface image registration system. At the initial setup, EPID images were compared with DRRs and a reference 3D surface image was obtained by the AlignRT system (Vision RT, London, UK). Surface images were acquired prior to every subsequent setup procedure. EPID acquisition was repeated when errors > 5 mm were reported.</p> <p>Results</p> <p>The mean random and systematic errors were 1.2 ± 2.3 mm and 0.3 ± 3.0 mm along the X axis, 0.0 ± 1.4 mm and 0.5 ± 2.0 mm along the Y axis, and 2.0 ± 1.8 mm and -0.7 ± 2.4 mm along the Z axis respectively. The positioning error detected by AlignRT along the 3 axes X, Y, and Z exceeded the value of 5 mm in 14.1%, 2.0%, and 5.1% measurements and the value of 3 mm in 36.9%, 13.6% and 27.8% measurements, respectively. Correlation factors calculated by linear regression between the errors measured by AlignRT and EPID ranged from 0.77 to 0.92 with a mean of 0.85 and SD of 0.13. The setup measurements by surface imaging are highly reproducible and correlate with the setup errors detected by EPID.</p> <p>Conclusion</p> <p>Surface image registration system appears to be a simple, fast, non-invasive, and reproducible method to analyze the set-up alignment in 3DCRT of prostate cancer patients.</p

Nocturia, Sleep-Disordered Breathing, and Cardiovascular Morbidity in a Community-Based Cohort

Background: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. Methodology/Principal Findings: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05). Conclusions/Significance: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension

Recent advances in radiotherapy

Radiation therapy has come a long way from treatment planning based on orthogonal radiographs with large margins around tumours. Advances in imaging and radiation planning software have led to three-dimensional conformal radiotherapy and, further, to intensity modulated radiotherapy (IMRT). IMRT permits sparing of normal tissues and hence dose-escalation to tumours. IMRT is the current standard in treatment of head and prostate cancer and is being investigated in other tumour sites. Exquisitely sculpted dose distributions (increased geographical miss) with IMRT, plus tumour motion and anatomical changes during radiotherapy make image guided radiotherapy an essential part of modern radiation delivery. Various hardware and software tools are under investigation for optimal IGRT

Testosterone Is Associated with Erectile Dysfunction: A Cross-Sectional Study in Chinese Men

Testosterone is essential for the regulation of erectile physiology, but the relationship between low testosterone and erectile dysfunction (ED) has not been firmly established.To examine the association between serum total, free and bio-available testosterone and ED in a population-based sample.A consecutive series of 1776 men aged 20–77 participated in the routine physical examination from September 2009 to December 2009 in Guangxi, China. ED was assessed using the five-item International Index of Erectile Function (IIEF-5) questionnaire. Total testosterone (TT), sex hormone binding globulin (SHBG) and other biochemical profiles were measured. Free testosterone (FT) and bio-available testosterone (BT) were calculated based on Vermeulen’s formula. Data were collected with regard to smoking, alcoholic drinking, physical activity and metabolic syndrome.The prevalence of ED (IIEF-5<22) was 47.6%. Men with ED were significantly older, and more prone to smoke cigarettes (≥20 cigarettes/day) or drink alcohol (≥3 drinks/week), and more likely to have elevated blood pressure (P = 0.036) or hyperglycemia (P<0.001) compared with those without ED. The significant increase in SHBG with age was parallel to its increase with increasing severity of ED (P<0.001). The obscure increase in TT across the ED status was detected without significance (P = 0.418), but TT was positively associated with ED after adjustment for age [odds ratio (OR)  = 1.02, 95% CI (confidence internal): 1.00–1.04]. FT and BT were inversely associated with ED (OR = 0.14, 95%CI: 0.06–0.33; OR = 0.92 (95%CI: 0.89–0.96, respectively) in the univariate analysis, and this inverse association appeared to be independent of smoking status, alcoholic drinking, physical activity, hyper-triglyceridemia and hyperglycemia.FT and BT are inversely related to worsening ED, whereas the positive association between TT and ED is most likely due to the increase in SHBG