Impact of weight-related advice from healthcare professionals on body mass index of patients in the USA.

OBJECTIVES: Healthcare professionals (HCPs) can help promote healthy eating and active living in patients. This study assessed the effects of weight-related advice from HCPs on change in body mass index (BMI) of patients in the USA. STUDY DESIGN: A 1-year follow-up study of 20,002 adults who participated in a nationally representative survey between 2004 and 2008. METHODS: Using the 2004-2008 Medical Expenditure Panel Survey data, 1-year BMI and weight status changes were compared between patients who did and did not report receiving advice on exercise or on restricted intake of fat and cholesterol from their HCPs. RESULTS: Patients who received weight-related advice had a greater increase in BMI compared with those who did not receive weight-related advice. Stratified by the baseline weight status of patients (i.e. normal weight, overweight or obese), adverse direction of BMI change was only significantly associated with advice on exercise. Patients who received advice to exercise more were more likely to move to a higher weight status than remaining at the same weight status, compared with patients who did not receive advice to exercise more. CONCLUSION: This study did not find that weight-related advice from HCPs had a positive impact on BMI loss in patients. On the contrary, patients who reported receiving weight-related advice from HCPs had worse weight outcomes 1 year later than patients who did not report receiving weight-related advice. Further research is warranted to elucidate the role of weight-related advice from HCPs on lifestyle change and obesity prevention and control.

Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway.

Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity. PDIA4 knockdown resulted in opposite outcomes. Moreover, results obtained in mice with spontaneous hepatoma indicated that PDIA4 deficiency significantly reduced hepatic tumorigenesis and cyst formation and increased mouse survival, tumor death, and caspases 3 and 7 activity. Mechanistic studies illustrated that PDIA4 negatively regulated tumor cell death by inhibiting degradation and activation of procaspases 3 and 7 via their mutual interaction in a CGHC-dependent manner. Finally, we found that 1,2-dihydroxytrideca-5,7,9,11-tetrayne, a PDIA4 inhibitor, reduced tumor development via enhancement of caspase-mediated cell death in TSA tumor-bearing mice. These findings characterize PDIA4 as a negative regulator of cancer cell apoptosis and suggest that PDIA4 is a potential therapeutic target for cancer.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Dietary resistant maltodextrin ameliorates testicular function and spermatogenesis in streptozotocin-nicotinamide-induced diabetic rats.

This study investigated the effect of resistant maltodextrin (RMD) on reproduction in streptozotocin (STZ)-nicotinamide-induced type 2 diabetic male rats. Forty male rats were induced with diabetes by a single intraperitoneal injection of STZ (50 mg kg(-1)) and nicotinamide (100 mg kg(-1)). Five groups were analysed in total: normal, diabetic rats without RMD, diabetic rats with RMD 1.2 g per 100 g diet (1×), with RMD 2.4 g per 100 g (2×), and with RMD 6.0 g per 100 g (5×). The groups of diabetic rats with the RMD supplement, compared to those without supplement, showed improved plasma glucose control, attenuated insulin resistance and recovery of testosterone level and spermatogenesis stage. The STZ-nicotinamide-induced diabetes mellitus (DM) caused a significant reduction in serum testosterone, testis androgen receptor (AR), steroidogenic acute regulatory protein (StAR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) protein, but a statistical recovery in each of these was observed in the 5× group. TUNEL-positive cells were observed in the diabetic without RMD group, and RMD treatment reduced apoptotic germ cells. The expression of Bax/Bcl2 was induced in the diabetic group and also significantly reduced in the 5× group. Dietary RMD may improve metabolic control in STZ-nicotinamide-induced diabetic rats and attenuate hyperglycaemia-related impaired male reproduction and testicular function.

Biochemical properties of the recurrent LMX1b truncated mutant carried in a Taiwanese family with nail-patella syndrome.

BACKGROUND: Loss of the DNA-binding activity of a transcription factor is detrimental to its function in responsive gene regulation. We diagnosed a Taiwanese family with nail-patella syndrome (NPS) whose members inherited the mutated LMX1b transcription factor with no DNA-binding homeodomain. The loss-of-function variants cause haploinsufficiency of LMX1b, leading to the clinical manifestation of NPS. The underlying molecular mechanism is unclear. OBJECTIVES: To test whether the recurrent pathogenic truncated LMX1b-R198X reported in our patients might be a functional protein. Its biochemical properties were explored. METHODS: The luciferase reporter driven by the human interleukin (IL)-6 gene promoter was assayed to measure the transcriptional activity of LMX1b. The nuclear localization of different enhanced green fluorescent protein-tagged LMX1b proteins was observed using fluorescence microscopy. Western blotting was employed to evaluate the expression of various transfected LMX1b constructs. RESULTS: LMX1b-R198X enhanced the IL-6 promoter activity activated by the wild-type LMX1b and diminished the promoter activity induced by phorbol 12-myristate 13-acetate. LMX1b-R198X carried out its effect differentially in the expression of various human genes. The nuclear localization of the wild-type LMX1b was disrupted by the C-terminus truncation. The protein stability exhibited by LMX1b-R198X appears to be much higher than that of the wild-type protein. CONCLUSIONS: We demonstrated that loss of function might not be the only way for mutated LMX1b to cause haploinsufficiency as the main pathogenic mechanism for NPS. LMX1b-R198X has less nuclear localization and higher stability than the wild-type protein; consequently, it might function as a competitor to sequester other effectors by protein-protein interaction to interfere with downstream transcriptional events.

Magnetic response of an ultrathin cobalt film in contact with an organic pentacene layer.

To emulate the interfacial regimes of a Co/Pc/Co spin-valve structure, we fabricated ultrathin pentacene/cobalt (Pc/Co) and cobalt/pentacene (Co/Pc) bilayers. Through measurement of the magneto-optical Kerr effect, we found the Co layer has its magnetic properties depend strongly upon the order of deposition. Further x-ray spectroscopy and microscopy investigation indicated Co/Pc was chemically stable, whereas Pc/Co was reactive and exhibited complex magnetization pattern. The different chemistry and magnetic configurations at interfaces could cause additional complication for spin injection.

Comparison of perforation risk among physicians, other medical professionals and general adults with acute appendicitis in Taiwan.

BACKGROUND: This study aimed to compare the risk of appendiceal perforation among physicians, other medical professionals and general adults, when hospitalized for acute appendicitis. METHODS: National population-based data for 92 143 patients with acute appendicitis, aged 20 years or more, who underwent appendicectomy or drainage of an appendiceal abscess in Taiwan from 1996 to 2001 were analysed retrospectively. The outcome measure was appendiceal perforation. Patients were categorized as physicians (Western medical doctors), other medical professionals (such as dentists or nurses) or general adults (not medical professionals). Adjusted odds ratios and 95 per cent confidence intervals (c.i.) were estimated by multiple logistic regression. RESULTS: Multivariable analysis showed that appendiceal perforation was 0.67 (95 per cent c.i. 0.46 to 0.96) and 0.78 (95 per cent c.i. 0.62 to 0.99) times less likely in physicians and other medical professionals respectively than in general adults, after adjusting for patient and admitting hospital characteristics, and for calendar year. CONCLUSION: The risk of perforation was significantly lower among physicians and other medical professionals than in general adults. Medical knowledge, familiarity with the healthcare system and better patient-doctor communication may have been contributory factors.

Erythrocyte spectrin's chimeric E2/E3 ubiquitin conjugating/ligating activity.

Spectrin is important for the shape and the physical properties of the red blood cell, such as deformability and resistance to mechanical stress. Previous findings from our laboratory indicated that human erythrocyte alpha-spectrin can facilitate formation of ubiquitin-spectrin adducts and conjugates. Computer analysis revealed domains that contained significant homologies to known consensus catalytic E2 and E3 sequences, and allowed us to develop a model for alpha-spectrin ubiquitin conjugating enzyme (E2) and ubiquitin protein ligase (E3) enzymatic activities. In order to identify the precise E2/E3 site(s), in the present study, a GST-fusion alpha-spectrin (2005-2415) recombinant protein was tested using a cell free in vitro ubiquitination assay. We found that cysteine 2071 and cysteine 2100 are critical for alpha-spectrin (2005-2415) E2/E3 activity. Furthermore, together with testing an additional 13 site-specific mutants, we also demonstrated that both Cys2071 and Cys2100 are capable of transferring ubiquitin from an E1 enzyme to target sites within alpha-spectrin (2005-2415).

Molecular orientation of evaporated pentacene films on gold: alignment effect of self-assembled monolayer.

Pentacene films deposited on self-assembled monolayers (SAMs) bearing different terminal functional groups have been studied by reflection-absorption IR, grazing angle XRD, NEXAFS, AFM, and SEM analyses. A film with pentacene molecules nearly perpendicularly oriented was observed on Au surfaces covered with an SAM of alkanethiol derivative of X-(CH2)(n)-SH, with X = -CH(3), -COOH, -OH, -CN, -NH(2), C(60), or an aromatic thiol p-terphenylmethanethiol. On the other hand, a film with the pentacene molecular plane nearly parallel to the substrate surface was found on bare Au surface. A similar molecular orientation was found in thinner ( approximately 5 nm) and thicker (100 nm) deposited films. Films deposited on different surfaces exhibit distinct morphologies: with apparently smaller and rod-shaped grains on clean bare Au surface but larger and islandlike crystals on SAM-modified surfaces. X-ray photoemission electron microscopy (X-PEEM) was used to analyze the orientation of pentacene molecules deposited on a SAM-patterned Au surface. With the micro-NEXAFS spectra and PEEM image analysis, the microarea-selective orientation control on Au was characterized. The ability to control the packing orientation in organic molecular crystals is of great interest in fabricating organic field effect transistors because of the anisotropic nature of charge transport in organic semiconducting materials.

Spectrin and ubiquitination: a review.

This review covers the observations leading to the conclusion that erythrocyte spectrin is a chimeric E2/E3 ubiquitin conjugating/ligating enzyme and the impact of this activity on the cell. Spectrin is important for the shape and the physical properties of the red blood cell, such as deformability and resistance to mechanical stress. The involvement of RBC spectrin in the ubiquitination process has been demonstrated. Human erythrocyte alpha-spectrin can facilitate formation of ubiquitin-spectrin adducts and conjugates in cell free systems (28). Computer analysis revealed domains that contained significant homologies to known consensus catalytic E2 and E3 sequences, and allowed us to develop a model for alpha-spectrin ubiquitin conjugating enzyme (E2) and ubiquitin protein ligase (E3) enzymatic activities. The model has been tested and the precise E2/E3 site(s) identified by site-specific mutational analyses using a GST-fusion alpha-spectrin(2005-2415) recombinant in an in vitroubiquitination assay (26). The results indicated that cysteine 2071 and cysteine 2100 are critical for alpha-spectrin(2005-2415) E2/E3 activity as expected. However, both Cys2071 and Cys2100 are capable of transferring ubiquitin from an E1 enzyme to target sites within alpha-spectrin(2005-2415). This revealed a redundancy of function for human RBC spectrin's chimeric E2/E3 ubiquitin conjugating/ligating activity. Since spectrin is the major structural component of the erythrocyte membrane skeleton, and it constitutes 20% of the total RBC membrane protein, its ubiquitination enzymatic activity could play an important role in both erythropoietic cells and mature RBCs. This could also be one reason for evolving this redundancy of function.

Osmotic demyelination syndrome: a potentially avoidable disaster.

Osmotic demyelination of the brain (ODS) is a dreaded complication that typically occurs several days after aggressive therapy for chronic hyponatraemia, but is eminently avoidable. In this teaching exercise, Professor McCance, an imaginary consultant, is asked to explain how he would have treated a 28-year-old female who had hyperkalaemia, hypoglycaemia, hypotension and hyponatraemia (118 mM) to prevent the development of ODS. He begins with a review of the physiology, including his own landmark work on chronic hyponatraemia associated with a contracted extracellular fluid volume. Adding quantitative analysis, the cause of the excessive rise in plasma sodium concentration is revealed, and a better plan for therapy is proposed.

RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma.

RARRES3 is a retinoid-inducible class II tumour-suppressor gene. This study analysed the expression of RARRES3 protein in normal, adenoma and carcinoma tissues of the colorectum and its correlation with tumour differentiation. The expression of RARRES3 protein in 151 paraffin-embedded colorectal tissues (11 distal normal mucosa, 20 adenoma and 120 colorectal adenocarcinoma) was determined by immunohistochemistry. RARRES3 protein was expressed in all 11 distal normal, 120 adjacent normal and 20 adenoma tissues. In distal normal tissues, RARRES3 protein was expressed at the highest levels in differentiated mucosal epithelial cells. Among 120 carcinoma tissues, RARRES3 protein was detected in 97.6% (40 out of 41), 79.4% (54 out of 68) and 17.3% (three out of 11) of well-, moderately and poorly differentiated tumours, respectively. The expression of RARRES3 protein was positively correlated to tumour differentiation (test for trend, P<0.0001). Also, levels of RARRES3 protein were found to be higher in the normal tissues adjacent to 14.6% (six out of 41), 51.5% (35 out of 68), and 90.1% (10 out of 11) of well-, moderately and poorly differentiated tumours, respectively. The decreases in tumour differentiation and RARRES3 expression were significantly correlated compared to the adjacent normal tissues (test for trend, P<0.0001). The prognostic implication of RARRES3 protein expression was studied in 107 tumour, and no statistical difference in survival was observed. The expression of RARRES3 protein was positively correlated to cellular differentiation of normal and adenocarcinoma tissues of the colorectum, which supports the role of RARRES3 in normal and malignant epithelial differentiation of colorectum. RARRES3 expression was decreased only in carcinoma tissue, which suggests that altered RARRES3 expression occurs late in colorectal carcinogenesis.

Rathke's cleft cyst presenting with hyponatremia and transient central diabetes insipidus.

We describe an 18-year-old female who complained of general weakness, nausea, vomiting, headache, and lightheadedness. On physical examination, she was euvolemic without visual or neurological deficits. The striking biochemical abnormality was hyponatremia (125 mmol/l). This hyponatremia met the laboratory diagnostic criteria for the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Two litres of normal saline were given per day for 4 days and this did not correct her hyponatremia. A spontaneous diuresis (6.6 l) developed in 1 day, causing a rise in her PNa of 26 mmol and a final PNa of 152 mmol/l. Magnetic resonance imaging revealed a dumbell-shaped intrasellar and suprasellar cyst. During transsphenoidal surgery, a Rathke's cleft cyst (RCC) lined with columnar epithelium containing mucoid material was resected. We speculate that the growing RCC may have produced critical compression over the stalk, thus contributing to the transition from SIADH with hyponatremia to transient central diabetes insipidus with hypernatremia.

Direct molecular interaction of a conserved yolk granule protein in sea urchins.

The regulation of yolk storage in oocytes and subsequent utilization in embryos is critical for embryogenesis. In sea urchins, the major yolk protein is made in the intestines, transported to the ovaries and accumulated in developing oocytes within membrane-bound vesicles comprising approximately 10% of the mass of an egg. Here, a non-yolk protein that accumulates specifically in yolk granules is reported. This protein was identified by cDNA cloning and, by use of antibodies to the recombinant protein, it was shown that this molecule is stored selectively in yolk granules of oocytes and embryos. No accumulation was seen in the accessory cells, testis, or intestines. In situ ribonucleic acid (RNA) hybridizations showed that the transcript accumulated only in oocytes, and was more highly concentrated in young oocytes. However, later in oogenesis, the messenger ribonucleic acid (mRNA) levels decreased significantly so that no signal was detectable in mature haploid eggs or at any later stage in development. However, by immunofluorescence and western blot analysis, the 30 kDa band was present throughout development. The predicted sequence of this protein shows that it is a member of the bep, HLC-32, EBP family of sea urchin proteins, but as it does not accumulate at the cell surface, nor in the hyaline layer in the two species studied here, as do other members of the family, it has been referred to as YP30 (30 kDa protein of the yolk platelet). To address its potential function, yeast two-hybrid analysis was performed to screen for proteins that potentially interact with YP30. It was found that it binds itself, and forms strongly interacting dimers. It is hypothesized that YP30 participates in the packaging and storage of major yolk protein during oogenesis, or in the utilization of the major yolk protein in development.

The absence of neuromas in beaks of adult hens after conservative trimming at hatch.

OBJECTIVE: To determine the effects of the amount of break removed and cauterisation time on neuroma formation in hens. DESIGN: A pathology study with controls. ANIMALS: Twenty domestic fowl were beak-trimmed. Three non-beak-trimmed domestic fowl were used as controls. PROCEDURE: Beaks of two age groups with two levels of beak removal and either 2 s or 4 s cauterisation, were investigated macroscopically and microscopically for deformities. RESULTS: Scattered trauma-associated neuromas were present in the beaks of pullets 10 weeks after moderate trimming at hatch. Neuromas were not present in beaks of adult hens that had been similarly trimmed. Sensory corpuscles were present 10 and 70 weeks after moderate trimming, though fewer in number than in intact control hens. In contrast, trauma-associated neuromas persisted in beaks of 70-week-old hens that had been severely trimmed at hatch. A range of deformities that were absent in moderately trimmed hens, were observed in hens with severely trimmed beaks. Receptors were not seen in severely trimmed beaks. CONCLUSION: Beak-trimming at hatch induces the formation of neuromas, regardless of the amount of tissue removed. There is a critical amount of beak tissue that can be removed, beyond which trauma-associated neuromas will not resolve, but will persist in mature hens.