Case Study: Extreme Weight Making Causes Relative Energy Deficiency, Dehydration and Acute Kidney Injury in a Male Mixed Martial Arts Athlete.

The aim of the present case study was to quantify the physiological and metabolic impact of extreme weight cutting by an elite male MMA athlete. Throughout an 8-week period, we obtained regular assessments of body composition, resting metabolic rate (RMR), VO2peak and blood clinical chemistry to assess endocrine status, lipid profiles, hydration and kidney function. The athlete adhered to a "phased" weight loss plan consisting of 7 weeks of reduced energy (ranging from 1300 - 1900 kcal.d-1) intake (phase 1), 5 days of water loading with 8 L per day for 4 days followed by 250 ml on day 5 (phase 2), 20 h fasting and dehydration (phase 3) and 32 h of rehydration and refuelling prior to competition (phase 4). Body mass declined by 18.1 % (80.2 to 65.7 kg) corresponding to changes of 4.4, 2.8 and 7.3 kg in phase 1, 2 and 3, respectively. We observed clear indices of relative energy deficiency, as evidenced by reduced RMR (-331 kcal), inability to complete performance tests, alterations to endocrine hormones (testosterone: 6 mmol.L-1). Moreover, severe dehydration (reducing body mass by 9.3%) in the final 24 hours prior to weigh-in induced hypernatremia (plasma sodium: 148 mmol.L-1) and acute kidney injury (serum creatinine: 177 μmol.L-1). These data therefore support publicised reports of the harmful (and potentially fatal) effects of extreme weight cutting in MMA athletes and represent a call for action to governing bodies to safeguard the welfare of MMA athletes

Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal

Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings. Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury. Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement. Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p

Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer

Introduction: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. Methods: Patients recruited prospectively to two multicenter trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level, and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients’ beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT / PET-CT were analysed using logistic regression. Results: Baseline and post-staging questionnaires were completed by 97 and 107 patients respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans, and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI, and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006 to 2.284, p=0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099 to 8.288, p=0.032), yet only 45/107 (42%) patients were aware of this attribute. Conclusions: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionising radiation, could influence preference

Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. METHODS: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression. RESULTS: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute. CONCLUSIONS: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

Time-dependent excitation and ionization modelling of absorption-line variability due to GRB 080310

We model the time-variable absorption of FeII, FeIII, SiII, CII and CrII detected in UVES spectra of GRB 080310, with the afterglow radiation exciting and ionizing the interstellar medium in the host galaxy at a redshift of z=2.42743. To estimate the rest-frame afterglow brightness as a function of time, we use a combination of the optical VRI photometry obtained by the RAPTOR-T telescope array -- which are presented in this paper -- and Swift's X-Ray Telescope observations. Excitation alone, which has been successfully applied for a handful of other GRBs, fails to describe the observed column-density evolution in the case of GRB 080310. Inclusion of ionization is required to explain the column-density decrease of all observed FeII levels (including the ground state 6D9/2) and increase of the FeIII 7S3 level. The large population of ions in this latter level (up to 10% of all FeIII) can only be explained through ionization of FeII, whereby a large fraction of the ionized FeII ions -- we calculate 31% using the Flexible Atomic (FAC) and Cowan codes -- initially populate the 7S3 level of FeIII rather than the ground state. This channel for producing a significant FeIII 7S3 level population may be relevant for other objects in which absorption lines from this level -- the UV34 triplet -- are observed, such as BAL quasars and Eta Carinae. This provides conclusive evidence for time-variable ionization in the circumburst medium, which to date has not been convincingly detected. However, the best-fit distance of the neutral absorbing cloud to the GRB is 200--400 pc, i.e. similar to GRB-absorber distance estimates for GRBs without any evidence for ionization. We find that the presence of time-varying ionization in GRB 080310 is likely due to a combination of the super-solar iron abundance ([Fe/H]=+0.2) and the low HI column density (log N(HI)=18.7). [abridged]Comment: 14 pages, 6 figures; accepted for publication in A&A (on August 8, 2012

Perceived patient burden and acceptability of whole body MRI for staging lung and colorectal cancer; comparison with standard staging investigations

Objectives – To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance. Methods – Patients recruited to multi-centre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/ satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1 low to 7 high). Results – 115 patients (median age 66.3 years; 67 males) completed follow-up and 103 baseline questionnaires. Sixty-nine (63.9%) reported “immediate” recovery from WB-MRI and 73 (65.2%) judged it “very acceptable”. Perceived WB-MRI burden was greater than for CT (p<0.001) and PET-CT (p<0.001). High distress and co-morbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression Beta=0.223, p=0.025; Beta=0.191, p=0.048; Beta = -0.186, p=0.059 respectively). Age (p=0.535), gender (p=0.389), ethnicity (p=0.081) and cancer type (p=0.201) were not predictive of WB-MRI burden. Conclusions: WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities. Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical co-morbidities, adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC