Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

Assessment of liver cirrhosis for patients with Child's A classification before hepatectomy using dynamic contrast-enhanced MRI.

AIM: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis. MATERIALS AND METHODS: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI. RESULTS: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%. CONCLUSIONS: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy.

An abbreviated Faecal Incontinence Quality of Life Scale for Chinese-speaking population with colorectal cancer after surgery: cultural adaptation and item reduction.

No instrument is available to assess the impact of faecal incontinence (FI) of quality of life for Chinese-speaking population. The purpose of the study was to adapt the Faecal Incontinence Quality of Life Scale (FIQL) for patients with colorectal cancer, assess the factor structure and reduce the items for brevity. A sample of 120 participants were enrolled. Internal consistency, test-retest reliability, and convergent and contrasted-groups validity were assessed. Construct validity was analysed using an exploratory and confirmatory factor analyses (CFA). The internal consistency (Cronbach's α of the total scale and four subscales = 0.98 and 0.97, 0.96, 0.92, 0.82 respectively), test-retest reliability (intraclass correlation coefficients ≥.98 for all scales with p < .001) and significant correlations of all scales with selected subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey and the Wexner scale suggested satisfactory reliability and validity. The severe FI group (with a Wexner score ≥9) scored significantly lower on the scale than the less severe FI group (with a Wexner score <9) did (p < .001). The CFA supported a two-factor structure and demonstrated an excellent model fit of the 15-item abbreviated version of the FIQL-Chinese. The FIQL-Chinese has satisfactory validity and reliability and the abbreviated version may be more practical and applicable.

A report on emergent uranyl binding phenomena by an amidoxime phosphonic acid co-polymer.

The development of technology to harvest the uranium dissolved in seawater would enable access to vast quantities of this critical metal for nuclear power generation. Amidoxime polymers are the most promising platforms for achieving this separation, yet the design of advanced adsorbents is hindered by uncertainty regarding the uranium binding mode. In this work we use XAFS to investigate the uranium coordination environment in an amidoxime-phosphonic acid copolymer adsorbent. In contrast to the binding mode predicted computationally and from small molecule studies, a cooperative chelating model is favoured, attributable to emergent behavior resulting from inclusion of amidoxime in the polymer. Samples exposed to seawater also display a feature consistent with a µ(2)-oxo-bridged transition metal, suggesting the formation of an in situ specific binding site. These findings challenge long held assumptions and provide new opportunities for the design of advanced adsorbent materials.

A human study model for nitric oxide research in sinonasal disease.

Sinus nitric oxide (NO) measurements present a novel and promising approach to help overcome difficulties and confounding variables associated with nasal NO measurements such as the nasal cycle, ostial patency, and individual contribution to total NO production of each sinus. Conflicting results reported on nasal NO measurements in various sinonasal diseases are presumed to originate from the variable diffusion of sinus NO into the nose where it is measured. This study presents a novel technique and research method for direct measurement of sinus NO. The authors' original technique of individual, non-destructive catheterization of the sinuses through their natural ostia is developed and refined to allow accurate measurements of NO produced in the sinuses. Our study indicates that reproducible catheterization of the sinuses through their natural ostia can be performed in the clinical research setting under local and topical anesthesia. The model can be used to test the effects of various conditions on nasal and sinus NO production in a variety of disease models and the variables affecting sinonasal gas exchange can be differentially studied. Volunteer healthy adult human subjects without nasal allergies are used. An endoscopic nasal exam with topical anesthesia followed by in vitro allergy testing is performed to determine eligibility. Sinus computerized tomography (CT) scans are used to delineate anatomic features and to calculate paranasal sinus volumes. Continuous flow sinus air sampling and NO measurement with a chemiluminescence analyzer is obtained through polyethylene tube catheters (PEC) placed endoscopically into an aerated major paranasal sinus. Catheters are introduced through natural ostia under local and topical anesthesia. Nasal and differential sinus NO measurements are performed.

Pain in patients with equal radiographic grades of osteoarthritis in both knees: the value of gray scale ultrasound.

OBJECTIVES: To investigate the association of ultrasound (US) features with pain and the functional scores in patients with equal radiographic grades of osteoarthritis (OA) in both knees. METHODS: Fifty-six consecutive patients with knee OA: 85 symptomatic knees (81 knees with medial pain) and 27 asymptomatic knees, and 10 healthy patients without knee OA as a control were enrolled. US was done by two ultrasonographers blinded to patient diagnoses. US features were semiquantitatively scored (0-3) when appropriate. RESULTS: In the OA group, common US findings were marginal osteophyte, suprapatellar synovitis, suprapatellar effusion (SPE), medial meniscus protrusion, medial compartment synovitis (MCS), lateral compartment synovitis, and Baker's cyst. Only SPE and MCS were significantly associated with knee pain. Visual analog pain scale (VAS) scores on motion were positively linearly associated with SPE and MCS (P < 0.01). Only MCS was degree-dependently associated with VAS scores at rest, the Western Ontario and McMaster Universities pain subscale, and the presence of medial knee pain (P < 0.01) after adjustments for age, gender, body mass index (BMI), radiographic grade, and other US features. In the control group, no US features were associated with knee pain. CONCLUSIONS: US inflammation features, including SPE and MCS, were positively linearly associated with knee pain in motion. MCS was also degree-dependently associated with pain at rest and the presence of medial knee pain. These findings show that synovitis was one important predictive factor of pain. Further studies to confirm the association of US features and pain are warranted.

Observational Study of the Association between Hyponatremia and Rhabdomyolysis in Patients Presenting to Hospital.

Hyponatremia may be a risk factor for rhabdomyolysis, but the association is not well defined and may be confounded by other variables. The aims of this study were to determine the prevalence and strength of the association between hyponatremia and rhabdomyolysis and to profile patients with hyponatremia. In a cross-sectional study of 870 adults admitted to hospital with rhabdomyolysis and a median peak creatine kinase of 4064 U/L (interquartile range, 1921−12,002 U/L), glucose-corrected serum sodium levels at presentation showed a U-shape relationship to log peak creatine kinase. The prevalence of mild (130−134 mmol/L), moderate (125−129 mmol/L), and severe (<125 mmol/L) hyponatremia was 9.4%, 2.5%, and 2.1%, respectively. We excluded patients with hypernatremia and used multivariable linear regression for analysis (n = 809). Using normal Na+ (135−145 mmol/L) as the reference category, we estimated that a drop in Na+ moving from one Na+ category to the next was associated with a 25% higher creatine kinase after adjusting for age, alcohol, illicit drugs, diabetes, and psychotic disorders. Multifactorial causes of rhabdomyolysis were more common than single causes. The prevalence of psychotic and alcohol use disorders was higher in the study population compared to the general population, corresponding with greater exposure to psychotropic medications and illicit drugs associated with hyponatremia and rhabdomyolysis. In conclusion, we found an association between hyponatremia and the severity of rhabdomyolysis, even after allowing for confounders.

Phytochemical prospection and evaluation of antimicrobial, antioxidant and antibiofilm activities of extracts and essential oil from leaves of Myrsine umbellata Mart. (Primulaceae).

The species Myrsine umbellata is a native plant of Brazil, whose barks are traditionally used in herbal medicine to treat liver disorders and combat leprosy. Therefore, the aim of the study was to identify the phytochemical prospection of ethanolic (EE) and acetonic (EA) extracts by colorimetric tests and by gas chromatography coupled to mass spectrometry (GC-MS) of the essential oil (EO) of M. umbellata leaves; evaluate the antimicrobial activity in front of standard ATCC strains by the broth microdilution technique; the antioxidant potential by DPPH reduction method and antibiofilm action by crystal violet assay and cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based on optical density. Phytochemical prospection of EE and EA detected the presence of free steroids, alkaloids, flavonoids (flavones, flavononoids, flavonols and xanthons) and tannins in both extracts (EE and EA) and saponins only in EE. In EO, the majority compounds identified were elixene, caryophyllene (E), spatulenol, d-Cadinene and aromadendrene. EA showed antimicrobial activity with MIC and MBC/MFC values ranging from 3.12 to 100 mg.mL-1, highlighting its efficiency on the Gram-positive strain S. epidermidis. EE showed antimicrobial potential in the range of 3.12 to 200 mg.mL-1, and the Gram-negative E. coli strain was the most susceptible. However, OE showed bacteriostatic potential against S. Typhimurium, S. Abaetetuba, P. aeruginosa, and S. epidermidis strains. The ability to sequester free radicals was evident in EA extract with antioxidant activity of 89.55% and in EE with 63.05%. The antibiofilm potential was observed in EE extract which eradicated the mature biofilm biomass of all tested bacteria with high activity (50% to 84.28%) and EO also showed antibiofilm effect on mature biofilm of UEL enteroaggregative E. coli, S. aureus and S. Enteritidis strains with biomass reduction percentage of 63.74%, 68.04% and 86.19%, respectively. These results indicate the potential of M. umbellata extracts and as a source of plant bioactivity for the development of new alternative strategies for the control of planktonic or biofilm-resistant microorganisms.

Toll-like receptor 2 deficiency improves insulin sensitivity and hepatic insulin signalling in the mouse.

AIMS/HYPOTHESIS: Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised that the inflammatory signals transduced by TLR2 contribute to insulin resistance. METHODS: Mice deficient in TLR2 were used to investigate the in vivo roles of TLR2 in initiating and maintaining inflammation-associated insulin resistance and energy homeostasis. RESULTS: We first recapitulated the observation with elevated expression of TLR2 and inflammatory cytokines in white adipose tissue and liver of ob/ob mice. Aged or high-fat-fed TLR2-deficient mice were protected from obesity and adipocyte hypertrophy compared with wild-type mice. Moreover, mice lacking TLR2 exhibited improved glucose tolerance and insulin sensitivity regardless of feeding them regular chow or a high-fat diet. This is accompanied by reductions in expression of inflammatory cytokines and activation of extracellular signal-regulated kinase (ERK) in a liver-specific manner. The attenuated hepatic inflammatory cytokine expression and related signalling are correlated with increased insulin action specifically in the liver in TLR2-deficient mice, reflected by increased insulin-stimulated protein kinase B (Akt) phosphorylation and IRS1 tyrosine phosphorylation and increased insulin-suppressed hepatocyte glucose production. CONCLUSIONS/INTERPRETATION: The absence of TLR2 attenuates local inflammatory cytokine expression and related signalling and increases insulin action specifically in the liver. Thus, our work has identified TLR2 as a key mediator of hepatic inflammation-related signalling and insulin resistance.

Successful treatment of erlotinib-induced acute hepatitis and acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review.

Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor, is a target therapy and approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents, including gefitinib and erlotinib, the common dose-limiting toxicities are diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above adverse effects, infrequent but potentially fatal and lethal entity complications include acute interstitial lung disease (ILD) and acute hepatitis. The incidence of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI agents induced acute hepatitis remains uncertain and cessation medication is current policy. Here we reported a case of erlotinib induced interstitial pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general weakness, treated with high dose pulse therapy and showed good recovery.

Foot pressure and center of pressure in athletes with ankle instability during lateral shuffling and running gait.

This study evaluates foot pressure and center of pressure (COP) patterns in individuals with ankle instability during running and lateral shuffling. Eleven participants with ankle instability (AI) and 11 normal subjects (Normal) performed running and lateral shuffling tasks. The outcome measures were foot progression angle, peak pressure, and displacement of COP during stance phase. During running, the foot progression angle, that is, the angle of foot abduction, was lower in the AI group (Normal: 13.46° ± 4.45°; AI: 8.78° ± 3.91°), and the 1st metatarsal contact pressure (Normal: 0.76 ± 0.47 N/cm(2)·kg; AI: 1.05 ± 0.70 N/cm(2)·kg) and the 3rd metatarsal peak pressure were higher in the AI (Normal: 0.96 ± 0.60 N/cm(2)·kg; AI: 1.54 ± 0.68 N/cm(2)·kg). The medial-lateral (M-L) COP in the late-stance phase of running for the AI group transferred faster from lateral to medial foot than the Normal group. For lateral shuffling, the AI group had greater peak pressure at the 1st (Normal: 0.76 ± 0.67 N/cm(2)·kg; AI: 1.49 ± 1.04 N/cm(2)·kg), 2nd (Normal: 0.57 ± 0.39 N/cm(2)·kg; AI: 0.87 ± 0.68 N/cm(2)·kg), 3rd (Normal: 0.70 ± 0.54 N/cm(2)·kg; AI: 1.42 ± 0.87 N/cm(2)·kg), and 4th (Normal: 0.52 ± 0.38 N/cm(2)·kg; AI: 1.12 ± 0.78 N/cm(2)·kg) metatarsal areas than the Normal group. The M-L COP located more laterally from the early to mid-stance phase in the AI compared with the Normal group. The findings suggest that COP displacement during lateral shuffle may be a factor in ankle instability while the foot progression angle during running may be a compensatory strategy.

Triggering of allostery in an enzyme by a point mutation: ornithine transcarbamoylase.

The origin of allostery is an unanswered question in the evolution of complex regulatory proteins. Anabolic ornithine transcarbamoylase, a trimer of identical subunits, is not an allosteric enzyme per se. However, when the active-site residue arginine-106 of the Escherichia coli enzyme is replaced with a glycine through site-directed mutagenesis, the resultant mutant enzyme manifests substrate cooperativity that is absent in the wild-type enzyme. Both homotropic and heterotropic interactions occur in the mutant enzyme. The initial velocity saturation curves of the substrates, carbamoyl phosphate and L-ornithine, conform to the Hill equation. The observed cooperativity depends on substrate but not enzyme concentration. The finding underscores the possibility that a single mutation of the enzyme in the cell could turn transcarbamoylation into a regulatory junction in the biosynthesis of L-arginine and urea.

Jar-opening challenges. Part 1: an apparatus for assessing hand and finger torques and forces in a jar-opening activity.

A simulated jar apparatus was developed to record hand kinetics and torque contribution of a digit during jar-opening activities. The design of the apparatus, namely a jar body and a lid, is similar to a commercial jam jar that is regularly seen in daily living. One six-axis force-torque transducer and a torque cell were mounted inside the jar lid to detect the external force exerted from the digit and fixed on to the jar body to record the overall torque generated by the hand and wrist respectively. The applications of the apparatus were used to test the twisting torque of the hand and to measure the applied forces of the digit, which are both important factors in opening a jar. The contribution of each digit relative to the total twisting torque of the hand could be obtained via the apparatus. The intraclass correlation coefficient of the repeated measurements of the obtained forces and moments for different counterweights was approximately 0.96-1.00, which indicates that the reliability of the measured components of the apparatus is high. The high coefficient of determination (r2 > 0.99) indicates high accuracy of prediction of the measured values with respect to the expected loads. The validation outcomes support the design rationale and actual body part of the simulated jar. In addition, understanding the contribution of a single digit in opening a jar was also achieved via the apparatus and model.

Effects of age and gender on the movement workspace of the trapeziometacarpal joint.

While researchers have suggested that joint mobility would probably be affected by age and gender, research findings often present discrepancies. Little research has been performed on the factors which effect mobility of the trapeziometacarpal (TMC) joint. The purpose of this study was to address the effects of age and gender on the ranges of motion of the normal TMC joint. Eighty normal subjects divided into four age groups participated in this study. The TMC joint motions were recorded using an electromagnetic tracking system. In order to achieve a maximal range of TMC joint motion which was defined as the maximal workspace, each subject was asked to perform actively maximal circumduction, flexion-extension, and abduction-adduction of the TMC joint. Numerical and statistical methods were used to compute the TMC workspace and to detect significant differences. A workspace-to-length ratio was determined as an index to examine the effects of the age and gender on the joint mobility. The results demonstrated that age and gender had significant influences on the TMC workspace among the groups studied. The understanding of TMC joint mobility under different age and gender conditions is achieved through this study. The findings can be used to report clinical measures in the determination of the extent of impairment of osteoarthritis as well as the outcomes between pre- and post-surgical (or non-surgical) interventions.

Jar-opening challenges. Part 2: estimating the force-generating capacity of thumb muscles in healthy young adults during jar-opening tasks.

This study discusses the force-generating capacity of thumb muscles during jar-opening tasks using two grip patterns: the power grip and the precision grip. This study develops a three-dimensional biomechanical model of the thumb to predict muscle forces in jar-opening activities based on external forces measured by a custom-designed jar device. Ten healthy subjects participated in the study. Each participant turned a jar lid of 66 mm diameter counterclockwise with maximal effort and preferred speed using both grip patterns. The average normal and tangential forces applied by the thumb to the jar lid show that the normal force is the primary contributive force for opening a jar. This normal force is approximately three times the tangential force. Muscular force-generating capacity measurements show that the major active muscles during a jar-opening activity for both grips include the flexor pollicis longus, flexor pollicis brevis, abductor pollicis brevis, adductor pollicis, and opponens pollicis. The total muscle force ratios for the precision grip and power grip with respect to externally applied forces are 5.6 and 4.7 respectively. These ratios indicate that the power grip pattern produces less muscle force per unit of external applied load. The technique proposed in this study provides a proper apparatus and model for measuring three-dimensional loads and estimating the force-generating capacity of each muscle and tendon of the thumb during jar-opening tasks.

Trends in blind and low vision registrations in Taipei City.

PURPOSE: To determine the overall reported incidence and causes of registrable blindness and low vision in Taipei, Taiwan, that have occurred in the previous 10 years. METHODS: Study data were obtained from disability identification registration forms completed between January 1995 and December 2004. Definitions of low vision and blindness were defined by WHO criteria: low vision included visual acuity worse than 6/18 (20/60) to a lower limit of 3/60 (20/400). Blindness was defined as visual acuity worse than 3/60 (20/400) in the better eye with best possible correction. RESULTS: There were 3151 registrations for visual impairment during the study period. A total of 239 registrations were excluded due to insufficient data. Of the remaining 2912 (1518 males and 1394 females), 640 males and 647 females were legally blind (44.20%). A total of 878 males and 747 females were partially sighted. The six leading causes of low vision and blindness, in decreasing frequency, were glaucoma, optic neuropathy, diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and myopic macular degeneration. CONCLUSIONS: The proportions of new registrations owing to glaucoma, diabetic retinopathy, age-related macular degeneration, and myopic macular degeneration have changed significantly since 2000; the proportion due to diabetic retinopathy has increased.