CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.
In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.


Evaluation of a Physical-Psychological Integrative (PPI) intervention for community-dwelling spinal cord injury survivors: Study protocol of a preliminary randomized controlled trial.
There is a considerably large group of community-dwelling spinal cord injury (SCI) survivors living with low quality of life. Physical inactivity, depression, and chronic pain are major problems faced by SCI survivors discharged from the acute phase of treatment or inpatient rehabilitation. This study aims to evaluate the feasibility, acceptability, and preliminary effects of a Physical-Psychological Integrative (PPI) online group intervention on community-dwelling SCI survivors' physical activity, depression, and chronic pain. This is a two-arm pilot randomized controlled trial with repeated measures (pre-, post-intervention, and 3-month follow-up) design. Seventy-two participants will be randomly assigned to two study groups. The PPI intervention group will receive a video program for physical activity training and eight-week online group psychological interventions using skills of group-based motivational interviewing and mindfulness-based stress reduction. The control group will receive an eight-week online didactic education programed. Focus-group interviews will be conducted post-intervention to explore their views about acceptance and suggested improvements to the intervention. The feasibility of study procedures and the acceptability of interventions will be evaluated. The effectiveness of the PPI intervention will be evaluated by leisure-time physical activity, depression, chronic pain, exercise efficacy, mindfulness, and quality of life. We will use the generalized estimating equation to assess intervention effects and content analysis for interview data. This study has received ethical approval from the Hong Kong Polytechnic University (HSEARS20210705004) and was registered in ClinicalTrials.gov (NCT05535400). This study will be the first to provide empirical data on the evaluation of an online-group intervention integrating both physical activity promotion and psychological approaches, aimed at reducing physical inactivity, depression, and chronic pain for community-dwelling SCI survivors in Hong Kong. The findings could provide evidence supporting the use of PPI intervention as a novel online group support, in addressing both the physical and psychological needs of community-dwelling SCI survivors.


Biosynthesis of 9-methylstreptimidone involves a new decarboxylative step for polyketide terminal diene formation.
9-Methylstreptimidone is a glutarimide antibiotic showing antiviral, antifungal, and antitumor activities. Genome scanning, bioinformatics analysis, and gene inactivation experiments reveal a gene cluster responsible for the biosynthesis of 9-methylstreptimidone in Streptomyces himastatinicus. The unveiled machinery features both acyltransferase- and thioesterase-less iterative use of module 5 as well as a branching module for glutarimide generation. Impressively, inactivation of smdK leads to a new carboxylate analogue unveiling a new mechanism for polyketide terminal diene formation.


Functional genomics of abiotic stress tolerance in cereals.
Abiotic stresses such as extreme temperatures, low water availability, high salt and mineral deficiencies or toxicities severely diminish productivity of cereal crops. These stresses are becoming increasingly important because of the declining availability of good quality water, land degradation and community pressures to move away from chemical intervention in agriculture. Of the major cereals, wheat and barley are grown in the most hostile and consequently lowest yielding environments. Extensive genetic studies and surveys of landrace and wild germplasm have indicated extensive variation for abiotic stress tolerance but this has been difficult to exploit due to the relatively poor background knowledge of the molecular basis for stress in these species. Interconnected signal transduction pathways that lead to multiple responses to abiotic stresses have been difficult to study using traditional approaches because of their complexity and the large number of genes and gene products involved in the various defensive and developmental responses of the plant. Functional genomics is now widely seen as providing tools for dissecting abiotic stress responses in wheat and barley, through which networks of stress perception, signal transduction and defensive responses can be examined from gene transcription, through protein complements of cells, to the metabolite profiles of stressed tissues.


Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial.
Patients with chronic fatigue syndrome (CFS) often complain of persistent fatigue even after conventional therapies such as pharmacotherapy, cognitive behavioral therapy, or graded exercise therapy. The aim of this study was to investigate in a randomized, controlled trial the feasibility and efficacy of isometric yoga in patients with CFS who are resistant to conventional treatments. This trial enrolled 30 patients with CFS who did not have satisfactory improvement after receiving conventional therapy for at least six months. They were randomly divided into two groups and were treated with either conventional pharmacotherapy (control group, n = 15) or conventional therapy together with isometric yoga practice that consisted of biweekly, 20-minute sessions with a yoga instructor and daily in-home sessions (yoga group, n = 15) for approximately two months. The short-term effect of isometric yoga on fatigue was assessed by administration of the Profile of Mood Status (POMS) questionnaire immediately before and after the final 20-minute session with the instructor. The long-term effect of isometric yoga on fatigue was assessed by administration of the Chalder's Fatigue Scale (FS) questionnaire to both groups before and after the intervention. Adverse events and changes in subjective symptoms were recorded for subjects in the yoga group. All subjects completed the intervention. The mean POMS fatigue score decreased significantly (from 21.9 ± 7.7 to 13.8 ± 6.7, P < 0.001) after a yoga session. The Chalder's FS score decreased significantly (from 25.9 ± 6.1 to 19.2 ± 7.5, P = 0.002) in the yoga group, but not in the control group. In addition to the improvement of fatigue, two patients with CFS and fibromyalgia syndrome in the yoga group also reported pain relief. Furthermore, many subjects reported that their bodies became warmer and lighter after practicing isometric yoga. Although there were no serious adverse events in the yoga group, two patients complained of tiredness and one of dizziness after the first yoga session with the instructor. Isometric yoga as an add-on therapy is both feasible and successful at relieving the fatigue and pain of a subset of therapy-resistant patients with CFS. University Hospital Medical Information Network (UMIN CTR) UMIN000009646.


Band Structure Engineering of Schiff-Base Microporous Organic Polymers for Enhanced Visible-Light Photocatalytic Performance.
Schiff-base networks (SBNs), as typical examples of nitrogen-doped microporous organic polymers (MOPs), exhibit promising application prospects owing to their stable properties and tunable chemical structures. However, their band structure engineering, which plays a key role in optical properties, remains elusive due to the complicated mechanisms behind energy level adjustment. In this work, a series of SBNs are fabricated by tailoring the ratio of p-phthalaldehyde and o-phthalaldehyde in the Schiff-base chemistry reaction with melamine, resulting in a straightforward as well as continuous tuning of their band gaps ranging from 4.4 to 1.4 eV. Consequently, SBNs can be successfully used as photocatalysts with excellent visible-light photocatalytic activity even under metal-free conditions. Significantly, electronic structures of SBNs are systematically studied by electrochemical and spectroscopic characterizations, demonstrating that the enhanced performance is ascribed to proper band structure and improved charge separation ability. More importantly, in combination with theoretical calculations, the band structure regulation mechanism and band structure-photocatalytic property relationship are deeply disclosed. The results obtained from this study will not only furnish SBN materials with excellent performance for solar energy conversion, but also open up elegant protocols for the molecular engineering of MOPs with desirable band structures.


Biochemical characterization of aminopeptidase N2 from Toxoplasma gondii.
Aminopeptidase N (APN) is a member of the highly conserved M1 family of metalloproteases, and is considered to be a valuable target for the treatment of a variety of diseases, e.g., cancer, malaria, and coccidiosis. In this study, we identified an APN gene (TgAPN2) in the Toxoplasma gondii genome, and performed a biochemical characterization of the recombinant TgAPN2 (rTgAPN2) protein. Active rTgAPN2 was first produced and purified in Escherichia coli. The catalytic activity of the enzyme was verified using a specific fluorescent substrate, H-Ala-MCA; the rTgAPN2 was relatively active in the absence of added metal ions. The addition of some metal ions, especially Zn2+, inhibited the activity of the recombinant enzyme. The activity of rTgAPN2 was reduced in the presence of the EDTA chelator in the absence of added metal ions. The optimum pH for enzyme activity was 8.0; the enzyme was active in the 3-10 pH range. The substrate preference of rTgAPN2 was evaluated. The enzyme showed a preference for substrates containing N-terminal Ala and Arg residues. Finally, bestatin and amastatin were shown to inhibit the activity of the enzyme. In conclusion, rTgAPN2 shared general characteristics with the M1 family of aminopeptidases but also had some unique characteristics. This provides a basis for the function of aminopeptidases and the study of drug targets.


Enantioselective Lactonization by π-Acid-Catalyzed Allylic Substitution: A Complement to π-Allylmetal Chemistry.
Asymmetric allylic alkylation (AAA) is a powerful method for the formation of highly useful, non-racemic allylic compounds. Here we present a complementary enantioselective process that generates allylic lactones via π-acid catalysis. More specifically, a catalytic enantioselective dehydrative lactonization of allylic alcohols using a novel PdII -catalyst containing the imidazole-based P,N-ligand (S)-StackPhos is reported. The high-yielding reactions are operationally simple to perform with enantioselectivities up to 99 % ee. This strategy facilitates the replacement of a poor leaving group with what would ostensibly be a better leaving group in the product avoiding complications arising from racemization by equilibration.


Cancer survival in Qidong between 1972 and 2011: A population-based analysis.
Population-based cancer survival is an improved index for evaluating the overall efficiency of cancer health services in a given region. The current study analysed the observed survival and relative survival of leading cancer sites from a population-based cancer registry between 1972 and 2011 in Qidong, China. A total of 92,780 incident cases with cancer were registered and followed-up for survival status. The main sites of the cancer types, based on the rank order of incidence, were the liver, stomach, lung, colon and rectum, oesophagus, breast, pancreas, leukaemia, brain and central nervous system (B and CNS), bladder, blood [non-Hodgkin's lymphoma (NHL)] and cervix. For all malignancies combined, the 5-year observed survival was 13.18% and the relative survival was 15.80%. Females had higher observed survival and relative survival (19.32 and 22.71%, respectively) compared with males (9.63 and 11.68%, respectively). The cancer sites with the highest five-year relative survival rates were the female breast, bladder, cervix and colon and rectum; followed by NHL, stomach, B and CNS cancer and leukaemia. The poorest survival rates were cancers of oesophagus, lung, pancreas and liver. Higher survival rates were observed in younger patients compared with older patients. Cancers of the oesophagus, female breast and bladder were associated with higher survival in middle-aged groups. Improved survival rates in the most recent two 5-year calendar periods were identified for stomach, lung, colon and rectum, oesophagus, female breast and bladder cancer, as well as leukaemia and NHL. The observations of the current study provide the opportunity for evaluation of the survival outcomes of frequent cancer sites that reflects the changes and improvement in a rural area in China.


[Standard perioperative management of patients treated with lithium can lead to hyperosmolar coma].
A 55-year-old woman with bipolar disorder who had been taking lithium for several years developed hyperosmolar coma following osteosynthesis of a hip fracture. The coma was attributed to decompensation of undiagnosed nephrogenic diabetes insipidus due to chronic lithium intake. The lengthy perioperative fasting and large fluid loading (necessitated by the anesthetic technique) led to acute hypernatremia. Closer monitoring and a different anesthetic strategy might have avoided this classical complication of chronic lithium therapy. The patient recovered after symptomatic treatment. We discuss the perioperative management of patients taking (or having taken) lithium, based on a review of the literature.


Safety and efficacy of self-expandable metal stents for obstructive proximal and distal large bowel cancer.
Self-expandable metal stents are often used to treat obstructive large bowel cancers. This study assessed the safety and efficacy of colonic stent insertion carried out in a district general hospital. Methods A retrospective review was carried out between 1 January 2007 and 28 February 2014 to identify patients who underwent stent insertion for malignant colorectal obstruction. Results Seventy-five patients (median age 75.2 years, 70.6% male) with primary colorectal cancer underwent stent insertion - 53 underwent semi-elective self-expanded metal stent insertion (for subacute bowel obstruction) and 22 had emergency stent inserted (for acute bowel obstruction). The majority (88%) had self-expanded metal stents inserted for palliation. Technical and clinical success rates were 98.7% and 91.2%, respectively. One patient had stent-related perforation; there was no procedure-related mortality. Conclusion This study shows that self-expanded metal stent insertion in malignant colorectal obstruction is safe and effective and can be successfully delivered in a district general hospital with high technical and clinical success rates.


Minimally invasive transiliac plate osteosynthesis for type C injuries of the pelvic ring: a clinical and radiological follow-up.
To evaluate radiological and functional outcome in patients treated with minimally invasive transiliac plate osteosynthesis for unstable pelvic injuries. Retrospective analysis of a prospective treatment protocol in a consecutive patient series. Level 1 trauma center. Between January 1998 and December 2005, 31 patients with type C injuries of the pelvic ring were treated with minimally invasive transiliac plate osteosynthesis. According to the AO classification, 16 patients had a C1-injury, 9 had a C2 fracture, and 6 patients sustained a C3 injury of the pelvic ring. Anterior-posterior, inlet, and outlet radiographs were obtained preoperatively, immediately postoperatively, and during follow-up. Clinical outcome was determined according to the Hannover pelvic outcome score. Posterior plate osteosynthesis for type C injuries of the pelvic ring. Preoperative and postoperative dislocation of the posterior pelvic ring, loss of reduction, implant failure, implant removal, clinical results of the pelvic injury and general limitations following the trauma. Maximum average dislocation of the posterior pelvic ring was 16.1 mm preoperatively; postoperatively, it was 6.1 mm. A total of 23 patients (74.2%) could be followed up after an average of 20 months (range 7-57 months). Seven patients underwent follow-up treatment at other hospitals closer to their respective residences, whereas 1 patient passed away in the early postoperative phase due to multiorgan failure. Loss of reduction occurred in 2 cases. The clinical outcome regarding the pelvis was very good in 8 cases, good in 9 cases, fair in 4 cases, and poor in 2 cases. Social reintegration according to the Hannover pelvic outcome score was complete in 9 cases, poor in 10 cases, and incomplete in 10 cases. Posterior plate osteosynthesis is a sufficiently stable method for the treatment of unstable pelvic ring injuries with a low risk of iatrogenic nervous tissue and vascular lesions. The disadvantages are limited reduction possibilities, the necessity of bilateral bridging of the sacroiliac joint in a unilateral injury, as well as a higher rate of symptomatic hardware.


Dear health minister: tend the garden but make sure you fence the crocodiles.
This paper offers lessons to in-coming health ministers on how they can act to reduce inequities and take action on social determinants. It draws on an interview study of twenty former Australian State, Territory and Federal health ministers about the extent to which they were able to do these things during their tenure. In order to take effective health equity action the health ministers advised: ensure evidence is used to develop a strong party policy platform for health equity; install policy entrepreneurs for health equity and social determinants in the health ministry; build popular constituencies through processes of deliberative democracy; establish context appropriate cross-department mechanisms to co-ordinate action on social determinants; and be elected in the context of a political party which values social justice and redistribution.


Attachment and spreading of baby hamster kidney cells to collagen substrata: effects of cold-insoluble globulin.
Studies have been carried out to determine the effects of cold-insoluble globulin (CIG) on the attachment and spreading of baby hamster kidney cells on various collagen substrata. Cell attachment to native collagen substrata occurred in the absence of CIG just as fast as attachment to dried collagen or gelatin substrata occurred in the presence of CIG. On the other hand, cell attachment to dried collagen or gelatin was markedly reduced in the absence of CIG. Cell spreading also occurred on native collagen in the absence of CIG; however, CIG was absolutely required for cell spreading to occur on dried collagen or gelatin. Finally, anti-CIG antiserum or lactoperoxidase treatment inhibited cell spreading on CIG-coated substrata but not on native collagen substrata. The data are discussed in terms of the interaction of fibroblasts with collagen in situ.


Compliance of NHS dental practice websites in Wales before and after the introduction of the GDC document 'Principles of ethical advertising'.
Objectives To evaluate the compliance of NHS dental practice websites in Wales, UK, with the 2012 GDC document Principles of ethical advertising, before its introduction (2011) and again after its introduction (2014).Methods All practices in Wales with an NHS contract and dental practice website were identified. The content of the website was evaluated to determine if it complied with the principles outlined in the 2012 GDC document Principles of Ethical Advertising.Results Twenty-five percent of the 446 practices sampled in 2011 had a website, compared to 44% of the 436 practices sampled in 2014. The principles best complied with were; displaying the name, geographic address, and telephone number of the practice (100% for both years). None of the websites compared the qualifications or skills of its practitioners to others, therefore 100% complied with this principle. Displaying team members' professional qualification and the country from which this is obtained was fairly well represented; 92% and 61% respectively in 2014; an improvement from only 50% and 49% respectively in 2011. Principles worst complied with were displaying the GDC's address (3% 2011; 9% 2014) or link to the GDC website (11% 2011; 7% 2014) and details of the practice complaints procedure (1% 2011; 5% 2014). Overall, no practice complied with all of the compulsory principles.Conclusion In both 2011 and 2014 no practice website was compliant with all the principles outlined in the 2012 GDC document Principles of ethical advertising. Reflecting results from previous studies, this study showed that compliance is slowly improving, yet over 4 years after the introduction of the mandatory principles, it remains that no practice website is 100% compliant.


Work engagement as a mediator between organizational commitment and job satisfaction among community health-care workers in China: a cross-sectional study.
The purpose of this study was to explore levels of organizational commitment, job satisfaction and work engagement among community health-care workers in China, and to examine spatial relationships of variables. Data were collected by Organizational Commitment Scale, Job Satisfaction Scale and Utrecht Work Engagement Scale from 1404 community health-care workers in Guangzhou and Shenzhen cities. Structural equation model was used to analyze relationships among three variables. Medium levels of organizational commitment, job satisfaction and work engagement were found among community health-care workers. Organizational commitment was positively correlated to work engagement (r = 0.564) and job satisfaction (r = 0.550). The path analysis indicated that total effect (β = 0.598) of organizational commitment on job satisfaction (R2 = 0.52) consisted of a direct effect (β = 0.264) and an indirect effect (β = 0.334), which was mediated positively by work engagement. Improvement in work engagement may lead to higher level of job satisfaction and organizational commitment.


Activation of monoamine oxidase by high molecular weight fractions of human plasma.
The activation of human platelet monoamine oxidase (MAO) and rat brain mitochondrial MAO ( RBM -MAO) by human plasma were studied. The deamination of two different substrates, tyramine and phenethylamine (PEA) was investigated. The increase in MAO activity in the presence of human plasma can be explained by the observed decrease in the apparent Km for the amine (tyramine, PEA). This activation pattern was the same both for human platelet MAO and RBM -MAO. The activating properties of human plasma were recovered in high molecular weight fractions after gel filtration.


The nuclear receptors constitutive active/androstane receptor and pregnane x receptor activate the Cyp2c55 gene in mouse liver.
Mouse CYP2C55 has been characterized as an enzyme that catalyzes synthesis of 19-hydroxyeicosatetraenoic acid (19-HETE), an arachidonic acid metabolite known to have important physiological functions such as regulation of renal vascular tone and ion transport. We have now found that CYP2C55 is induced by phenobarbital (PB) and pregnenolone 16alpha-carbonitrile (PCN) in both mouse kidney and liver. The nuclear xenobiotic receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) regulate these drug inductions: CYP2C55 mRNA was increased 25-fold in PB-treated Car(+/+) but not in Car(-/-) mice and was induced in Pxr(+/+) but not Pxr(-/-) mice after PCN treatment. Cell-based promoter analysis and gel shift assays identified the DNA sequence (-1679)TGAACCCAGTTGAACT(-1664) as a DR4 motif that regulates CAR- and PXR-mediated transcription of the Cyp2c55 gene. Chronic PB treatment increased hepatic microsomal CYP2C55 protein and serum 19-HETE levels. These findings indicate that CAR and PXR may play a role in regulation of drug-induced synthesis of 19-HETE in the mouse.


Styleworts under the microscope: a taxonomic account of Levenhookia (Stylidiaceae).
A taxonomic revision of the Australian endemic genus Levenhookia R.Br. (Stylidiaceae) recognises 12 species, of which L. aestiva Wege, sp. nov. from south-western Australia is newly described. Levenhookia preissii (Sond.) F.Muell. is lectotypified and recircumscribed as a Swan Coastal Plain endemic, resulting in its addition to the Threatened and Priority Flora List for Western Australia. Lectotypes are also selected for L. dubia Sond., L. leptantha Benth., L. sonderi (F.Muell.) F.Muell. and L. stipitata (Benth.) F.Muell. ex Benth. Verification of herbarium records has expanded the known distribution of L. murfetii Lowrie & Conran and L. pulcherrima Carlquist and has confirmed the widespread distribution of L. dubia across southern Australia including Tasmania, where it is currently listed as extinct-surveys based on information gleaned from historical collections may lead to its rediscovery in this State. Descriptions, distribution maps and photographs for all species are provided along with a key to species.


Metastatic pancreatic cancer: is gemcitabine still the best standard treatment? (Review).
Pancreatic ductal adenocarcinoma is the fourth cause of death in the Western world. Surgery remains the only treatment offering an advantage in terms of overall survival (5-year survival range, 15-25%), but unfortunately only 10-20% of patients present resectable disease at the time of diagnosis. Hence chemotherapy, possibly combined with radiation therapy, remains the only treatment option aimed at palliation of symptoms and ensuring a better quality of life. Notwithstanding the efforts to find more effective therapies for the treatment of pancreatic cancer, significant results have not yet been achieved. Increasing interest has focused on integrated treatments, i.e. chemotherapy combined with targeted therapies, and a better selection of patients. This study examines the principal clinical trials that will help give clinicians an overview of the progress made in the systemic therapy for advanced pancreatic cancer patients in recent years.


Effect of nitric oxide synthase inhibition on intrarenal oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging.
To investigate the feasibility of studying renal effects of nitric oxide synthase inhibition (NOSi) in humans by blood oxygenation level-dependent (BOLD) MRI. Nitric oxide (NO) is known to play a key role in the pathophysiology of hypertension and previous reports suggest reduced bioavailability of NO in the kidneys of hypertensive rats and hence show reduced response to NOSi using BOLD MRI. Ability to perform similar studies in humans could potentially lead to detection of early changes before development of symptoms, and to monitor novel interventions targeted toward improved NO bioavailability. The specific goals for this study were: (1) to examine whether lower doses and dose rate of administration of NOSi such as those previously used in humans can be detected by BOLD MRI in rat kidneys, (2) to compare changes in R2* to direct measures of renal medullary oxygen levels and blood flow using invasive probes (OxyLite/OxyFlo), and (3) to examine for the first time the effect of NOSi on intrarenal oxygenation in humans. In rat kidneys, acute changes in renal tissue oxygenation induced by different doses (2, 4, and 10 mg/kg) of N-nitro-L-arginine methyl ester were studied in 36 Sprague Dawley rats, which were equally divided into BOLD MRI and OxyLite/OxyFlo groups. Similarly in humans, acute changes in renal oxygenation were induced by 2 different NOS inhibitors NG-monomethyl-L-arginine (4.25 mg/kg) in 7 volunteers and N-nitro-L-arginine methyl ester (2 mg/kg and 4 mg/kg) in 6 healthy young volunteers. A multiple gradient echo sequence was used in both rats (TE = 4.4-57.8 milliseconds with 3.6 milliseconds interecho spacing) and humans (TE = 6.4-40.8 milliseconds with a 2.3 milliseconds interecho spacing) to acquire 16 T2*-weighted images. R2* maps were constructed by fitting a single exponential decay to the image data on pixel by pixel basis. R2* measurements in the cortex and medulla were performed by regions of interest analysis. Measurements were performed before and during infusion of NOSi. In rats, NOSi decreased medullary pO2 and blood flow in a dose-dependent manner, and BOLD MRI showed an increase in medullary R2* consistent with the invasive pO2 measurements. In humans, BOLD MRI similarly showed an increase in medullary and cortical R2* after NOSi in a dose-dependent manner. In both rats and humans, the R2* values fell back toward baseline before the end of the infusion period. Comparison of BOLD MRI measurements with those using invasive probes suggests that changes in blood flow are at least partly responsible for observed changes with BOLD MRI. Monitoring changes after NOSi by renal BOLD MRI in vivo in human kidneys are feasible, and preliminary findings are consistent with observations in rat kidneys. Future studies are warranted to fully understand the apparent reversal in R2* changes during the infusion of NOSi.


Psychotherapy and classification: psychological, psychodynamic, and cognitive aspects.
Psychotherapists' needs for diagnoses and classification in terms of the psychosocial model of a disorder are different from those of the medical model of psychiatric disorders as predominantly used in the DSM and ICD manuals. The challenges emerging from these different diagnostic needs and traditions of diagnosing are formulated as three dichotomies: grouping according to a medical versus psychosocial perspective; using objective versus hermeneutic methodology with the claim of producing factual knowledge versus constructivistic self-interpretation; defining a lasting categorical diagnostic state for the present time versus a versatile monitoring process with attention to the most salient dysfunction at a given time. Disorder-specific psychotherapy cannot overcome these dichotomies. It needs to combine them, and by doing so to reconcile them. It would be desirable that future diagnostic manuals meet psychotherapists' diagnostic needs.


Geographic variation in the relationship between body mass index and the built environment.
Studies examining associations between weight status and neighborhood built environment (BE) have shown inconsistent results and have generally focused on urban settings. However, many Americans do not live in metropolitan areas and BE impacts may be different outside of metropolitan areas. We sought to examine whether the relationship between body mass index (BMI) and neighborhood BE exists and varies by geographic region across small towns in the United States. We conducted telephone surveys with 2156 adults and geographic information systems data in nine towns located within three geographic regions (Northeast, Texas, Washington) in 2011 and 2012. Multiple regression models examined the relationship between individual BMI and BE measures. Most physical activity variables were significantly associated with lower BMI in all geographic regions. We saw variation across geographic region in the relationship between characteristics of the BE variables and BMI. Some perceived and objectively-measured characteristics of the BE were significantly associated with adult BMI, but significant relationships varied by geographic region. For example, in the Northeast, perceived attractiveness of the neighborhood as a reason for why they chose to live there was associated with lower BMI; in Texas, the perceived presence of a fast food restaurant was negatively associated with BMI; in Washington, perceived presence of trees along the streets was associated with lower BMI. Our findings suggest that regional variation plays a role in the relationship between adult BMI and BE characteristics in small towns. Regardless of geographic location, interventions should encourage utilitarian walking and other forms of physical activity.


[Renal damage caused by Rhupus syndrome associated with anti-neutrophil cytoplasmic antibodies vasculitis and cryoglobulinemia].
We analyzed the clinicopathological characteristics of one patient with Rhupus syndrome associated nephropathy in Peking University People's Hospital, and reviewed the related literature. The patient was a middle aged female. She developed rheumatoid arthritis first, and then manifested mild systemic lupus erythematosus together with positive anti-neutrophil cytoplasmic antibodies (ANCA) and cryoglobulinemia several years later. The renal biopsy was performed and manifested as lupus nephritis. The transmission electron microscopy revealed cryoglobulinemia associated renal damage. This report shows that the clinicopathological characteristics in patients with Rhupus syndrome associated nephropathy are complicated. The renal pathology can be used as a diagnostic tool.


Environmental abundances of the non-native round goby Neogobius melanostomus influence feeding of native fish predators.
The authors assessed the importance of the round goby Neogobius melanostomus as prey for three native predatory fish species, Atlantic cod Gadus morhua, European perch Perca fluviatilis and northern pike Esox lucius, in a northern and southern area of the Baltic Proper, using a combination of visual analysis and DNA metabarcoding of predator stomach contents. To explore the influence of environmental abundances of N. melanostomus on predation, they related the occurrence of N. melanostomus in predator diets to its abundance in survey fishing. Gadus morhua and E. lucius in the southern area showed the highest tendency to feed on N. melanostomus when it was abundant, as N. melanostomus occurred in up to 100% of stomachs and constituted up to 88% of the total diet volume proportion. The diet contribution of N. melanostomus was associated with N. melanostomus abundances for G. morhua and E. lucius, and when N. melanostomus was abundant, these predators exhibited lower prey richness and a higher degree of piscivory. G. morhua and P. fluviatilis also fed less on crustacean prey when N. melanostomus was abundant. The high importance of N. melanostomus in diets of native fish predators may modify indirect interactions between N. melanostomus and native prey species in invaded coastal communities.


Sheep model of haemodialysis treatment.
More than two million patients received haemodialysis (HD) in 2013. Many methods for improving dialysis therapy outcomes have been tested. Nevertheless, patients continue to experience high morbidity and mortality rates. We aimed to develop an animal model of HD treatment to study methods that would prevent the adverse effects of renal replacement therapy. The study was conducted using six male Merino sheep. The animals underwent a two-step bilateral nephrectomy, and a permanent dual-lumen catheter was inserted into the jugular vein. In each animal, 10 short, daily HD treatments were conducted. The dialysis prescription was adjusted individually to each animal. Measures of dialysis adequacy (spKt/V and urea reduction ratio [URR]) were calculated for each HD treatment. All animals remained in a good clinical state during the experiment. However, a sustained decrease in red blood cell count was detected. The average URR was 0.65 ± 0.01, whereas the calculated spKt/V was approximately 1.16 ± 0.03. Neither hyperphosphataemia nor a significant decline in serum albumin concentrations were detected during the study. A sustained increase in serum potassium concentrations was detected on consecutive days of the experiment. All sheep survived the treatment and were euthanized at the end of the experiment. In conclusion, we developed a reproducible sheep model of HD treatment. The gentle nature and specific anatomical features of sheep provided easy blood access and allowed us to perform HD without pharmacological intervention. However, some differences in sheep physiology relative to human physiology must be considered when interpreting the results of the study.


Mid-term follow-up outcomes of 2-staged hybrid coronary revascularization compared with off-pump coronary artery bypass for patients with multivessel coronary artery disease.
Two-staged hybrid coronary revascularization (HCR) is a novel procedure in selected patients with multivessel coronary artery disease. However, few studies are available on the mid-term or long-term outcomes of this 2-staged procedure as compared to off-pump coronary artery bypass (OPCAB). To compare in-hospital and mid-term follow-up outcomes of 2-staged HCR with OPCAB in patients with multivessel coronary artery disease. The present retrospective study analyzed the data from 73 patients who underwent the 2-staged HCR (HCR group) during 2012-2014 at the heart center. Three hundred and eighty-three patients who underwent conventional OPCAB by the same surgeon were selected for the comparative analysis performed on in-hospital and mid-term follow-up outcomes between the two groups. No significant difference was observed in the preoperative outcome between the two groups. The HCR group had a shorter operation duration (152.9 ±43.8 vs. 262.6 ±51.8 min, p < 0.05), less bleeding (558.6 ±441.3 vs. 1035.5 ±613.3 ml, p < 0.05), shorter mechanical ventilation (9.4 ±7.4 vs. 19.0 ±18.3 h, p < 0.05), and less blood transfusion (12 (16.4%) vs. 200 (52.2%), p < 0.05). The mean follow-up duration was 25.0 ±9.6 months in the HCR group and 22.8 ±10.6 months in the OPCAB group. The incidence of major adverse cardiac or cerebrovascular events (MACCE) was similar in both groups (4 (5.5%) vs. 10 (2.8%), p = 0.408). The estimated 3-year survival was similar in both groups (log-rank χ2 = 1.041, p = 0.308). The 2-staged HCR is a safe and effective surgical procedure and may offer similar mid-term follow-up outcomes to OPCAB.


Laboratory Diagnostics and Quality of Blood Collection.
Diagnostic blood samples collected by phlebotomy are the most common type of biological specimens drawn and sent to laboratory medicine facilities for being analyzed, thus supporting caring physicians in patient diagnosis, follow-up and/or therapeutic monitoring. Phlebotomy, a relatively invasive medical procedure, is indeed critical for the downstream procedures accomplished either in the analytical phase made in the laboratory or in the interpretive process done by the physicians. Diagnosis, management, treatment of patients and ultimately patient safety itself can be compromised by poor phlebotomy quality. We have read with interest a recent article where the authors addressed important aspects of venous blood collection for laboratory medicine analysis. The authors conducted a phlebotomy survey based on the Clinical and Laboratory Standard Institute (CLSI) H03-A6 document (presently replaced by the GP41-A6 document) in three government hospitals in Ethiopia to evaluate 120 professionals (101 non-laboratory professionals vs. 19 laboratory professionals) as regards the venous blood collection practice. The aim of this mini (non-systematic) review is to both take a cue from the above article and from current practices we had already observed in other laboratory settings, and discuss four questionable activities performed by health care professionals during venous blood collection. We refer to: i) diet restriction assessment; ii) puncture site cleansing; iii) timing of tourniquet removal and; iv) mixing specimen with additives.


Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.
Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS) inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors are involved in reducing neuronal cell death due to toxic conditions, especially phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified whether genetic vulnerability to neurotoxic states is present in cortical neurons isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the pathogenesis of stroke as well as apoptosis of cortical neurons isolated from SHRSP. We also examined the mechanisms necessary to reduce apoptosis under neurotoxic states using ultrastructural and biochemical techniques. Cortical neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin-like growth factor (IGF), rescued neurons from NO- and NMDA-mediated neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these growth factors against NO-mediated toxicity. The data thus indicate that genetic factors related to neuronal vulnerability to apoptosis are involved in the pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated by growth factors, is closely related to protective effects against NO- and NMDA-mediated toxicity in cortical neurons, especially those isolated from SHRSP. Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked to the inadequate activation of signaling pathways in the downstream of protein tyrosine kinases.


Most Care®: a minimally invasive system for hemodynamic monitoring powered by the Pressure Recording Analytical Method (PRAM).
Invasive hemodynamic monitoring is a cornerstone of the care of critically ill and hemodynamically unstable patients in both intensive care units and operating rooms. The assessment of cardiac output by means of the pulmonary artery catheter has been considered the clinical gold standard. Nevertheless, several concerns have been raised regarding its invasiveness, usefulness, and associated complica-tions. These disadvantages have led to the development, during the last years, of a number of less invasive technologies for cardiac output determination. Among them, those based on the analysis of a peripheral arterial waveform have become commonly used. Most Care(®) is a minimally invasive arterial pressure based monitor powered by the Pressure Recording Analytical Method (PRAM), the only algorithm that does not require prior calibration or pre-calculated parameters and which is based of flow. PRAM provides the measurement of the main factors of hemodynamics, such as systemic blood pressures, stroke volume, cardiac output, and vascular resistances. Moreover, dynamic indices of fluid responsiveness are continuously displayed. In the present paper, we reviewed the current literature focusing on advantages and limitations of PRAM.


The altered activity of P53 signaling pathway by STK11 gene mutations and its cancer phenotype in Peutz-Jeghers syndrome.
Peutz-Jeghers syndrome (PJS) is caused by mutations in serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been connected to P53 pathway. PJS probands with STK11 mutation were included in the function analysis. P53 activity elevated by STK11 mutants was investigated using dual-luciferase reporter assay in vitro after constructing expression vectors of STK11 wild type and mutants generated by site-directed substitution. The association between the P53 activity and clinicopathological factors was analysis, especially the cancer history. Thirteen probands with STK11 mutations were involved, and within the mutations, c.G924A was novel. P53 activity elevation caused by 6 truncating mutations were significantly lower than that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5 families. Within them, P53 activity was reduced and cancer occurred before 40 in 2 families, while it was not significantly changed and cancers happened after 45 in the other 3 families. The affected P53 activity caused by STK11 mutations in PJS patients is significantly associated with protein truncation, while cancer risk in PJS can be elevated through pathways rather than P53 pathway. P53 activity test is probably a useful supporting method to predict cancer risk in PJS, which could be helpful in clinical practice.


Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.
The release of enveloped viruses from infected cells often requires a virally encoded activity, termed a late-budding domain (L domain), encoded by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one of three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither YPDL nor PPXY-type L domains require ESCRT-I. Here, we show that ESCRT-I and other class E vacuolar protein sorting (VPS) factors are linked by a complex series of protein-protein interactions. In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX, a mammalian orthologue of the yeast class E VPS factor, Bro1. Expression of certain ESCRT-III components as fusion proteins induces a late budding defect that afflicts all three L-domain types, suggesting that ESCRT-III integrity is required in a general manner. Notably, the prototype YPDL-type L domain encoded by equine infectious anemia virus (EIAV) acts by recruiting AIP-1/ALIX and expression of a truncated form of AIP-1/ALIX or small interfering RNA-induced AIP-1/ALIX depletion specifically inhibits EIAV YPDL-type L-domain function. Overall, these findings indicate that L domains subvert a subset of class E VPS factors to mediate viral budding, some of which are required for each of the L-domain types, whereas others apparently act as adaptors to physically link specific L-domain types to the class E VPS machinery.


[Malignant neuroleptic syndrome under metoclopramide and neuroleptics in anuria].
A patient with myeloma nephropathy and acute, probably diclofenac-induced renal failure developed a neuroleptic malignant syndrome (NMS) during treatment with metoclopramide and neuroleptics. These drugs were withdrawn, symptomatic treatment of NMS was started and the patient was hemodialyzed because of uremia. During hemodialysis, the patient's condition improved dramatically and NMS did not recur during her further stay in the hospital. The temporal relationship between metoclopramide administration and the development of NMS, as well as the rapid reversal of NMS, suggest that NMS in this patient was caused by metoclopramide and not by neuroleptic drugs. Thus, metoclopramide should be used with caution in patients with renal failure and patients should be monitored closely for the development of neuroleptic malignant syndrome. Hemodialysis may be therapeutically effective in certain patients with metoclopramide-induced NMS.


An overview of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for the anesthesiologist.
Anesthesiologists face several perioperative challenges when patients need cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion. To adequately care for these patients, anesthesiologists must understand the goals and objectives of the operation in addition to having a basic knowledge of the chemotherapeutic drugs that are frequently used. Optimal anesthetic management of patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion requires control of a complex interplay of physiologic mechanisms, including hyperthermia, abdominal hypertension, electrolyte abnormalities, coagulopathies, increased cardiac index, oxygen consumption, and decreased systemic vascular resistance. As this surgery continues to gain popularity among oncologic surgeons, further studies that clearly define the chemistry, pharmacokinetics, pharmacodynamics, and end points of efficacy need to be performed to elucidate optimal perioperative management.


[The assessment of bacterial flora and antibiotic-sensitivity of bacteria isolated from conjunctival sac, skin of the eyelids and inflammatory lesions in patients with acne vulgaris and rosacea].
To evaluate bacterial flora of conjunctival sac, the skin of the eyelids and inflammatory lesions in patients with acne vulgaris, rosacea and of healthy people. Bacterial colonization of conjunctival sac, the skin of the eyelids and skin lesions is more frequent in patients with acne vulgaris and rosacea. Because antibiotic resistant strains of bacteria are quite often met, it seems important to determine antibiotic-sensitivity of isolated bacteria. 178 people underwent bacteriological examination of conjunctival sac, skin of the eyelids and skin lesions: 64 patients with acne vulgaris, 59 patients with rosacea and 55 healthy persons. Microorganisms were identified with laboratory techniques with the use of bio-Merieux kits and determination of drug-sensitivity was performed with recognized laboratory techniques. Positive cultures and general frequencies of the isolations were found to be higher in both groups in comparison with the reference group (the group of clinically healthy people). In healthy persons practically the only saprophytic bacteria--the most often S. epidermidis and S. viridans--were isolated. Whereas in patients suffering from acne vulgaris and rosacea the pathogenic bacteria--S. aureus, P. fluorescens, P. acnes, P. aeruginosa--were additionally isolated. Different spectrum of sensitivity to antibiotics of bacteria isolated from conjunctival sac, the skin of the eyelids and skin lesions in the cases of acne vulgaris and rosacea was proved. 1. In the cases of acne vulgaris the majority of isolated bacteria from conjunctival sac included Streptococcus spp., Staphylococcus spp. and Enterobacteriaceae. 2. In the severe cases of rosacea the main bacteria found in conjunctival sac were S. aureus, S.pyogenes, P.aeruginosa, E. faecalis, A. baumanii, P. fluorescens. 3. Because of changeable drug-sensitivity of bacterial strains, it seems to be necessary to perform individual culture and antibiogram in every patient with inflammatory lesions, in particular in clinically severe and resistant to therapy cases of acne vulgaris and rosacea. 4. The higher frequency of the bacterial colonisations in the conjunctival sac in patients with acne vulgaris and rosacea can be a potential source of ocular infections in the cases of local and systemic disorders of protective mechanisms. 5. Estimation of bacterial flora and antibiotic sensitivity of bacteria isolated from conjunctival sac, the skin of the eyelids and skin lesions should be perform, especially when patients are prepared for eye surgery.


Tropomyosin or not tropomyosin, what is the relevant allergen in house dust mite and snail cross allergies?
Since tropomyosin is cross reactive in many arthropods, it was assumed that this highly conserved protein could be responsible for cross reactions in house dust mite (HDM) allergic patients who experienced adverse reactions after crustacean and mollusc ingestion. Here we report two clinical cases where the role of tropomyosin is a matter of debate. In the first case, the clinical history, as well as the results of in vivo and in vitro investigations, are in favour of a shrimp allergy without any snail allergy in a patient sensitized to HDM. In the second, the clinical history and the cutaneous tests are in favour of an allergy to snails without any allergy to shrimps in a patient suffering from HDM allergies. The clinical presentation is different in shrimp and snail allergies. In shrimp allergy, symptoms are mainly urticaria or angio-oedema. In snail allergies, adverse reactions are especially severe asthma. Shrimp tropomyosin is a dominant allergen in crustaceans whereas has a much less prominent role in HDM sensitization. Cross reactivities between HDM and snails have been confirmed by inhibition experiments. However, tropomyosin appears to be a minor allergen or even is not involved in snail allergy. It is necessary to clarify the allergens shared between HDMI and snails. The effects of HDM immunotherapy in snail allergy are questioned. Knowledge of taxonomy can contribute to more precise evaluation of cross reactivities between crustaceans and molluscs.


Fabrication of 3D core-shell multiwalled carbon nanotube@RuO2 lithium-ion battery electrodes through a RuO2 atomic layer deposition process.
Pushing lithium-ion battery (LIB) technology forward to its fundamental scaling limits requires the ability to create designer heterostructured materials and architectures. Atomic layer deposition (ALD) has recently been applied to advanced nanostructured energy storage devices due to the wide range of available materials, angstrom thickness control, and extreme conformality over high aspect ratio nanostructures. A class of materials referred to as conversion electrodes has recently been proposed as high capacity electrodes. RuO2 is considered an ideal conversion material due to its high combined electronic and ionic conductivity and high gravimetric capacity, and as such is an excellent material to explore the behavior of conversion electrodes at nanoscale thicknesses. We report here a fully characterized atomic layer deposition process for RuO2, electrochemical cycling data for ALD RuO2, and the application of the RuO2 to a composite carbon nanotube electrode scaffold with nucleation-controlled RuO2 growth. A growth rate of 0.4 Å/cycle is found between ∼ 210-240 °C. In a planar configuration, the resulting RuO2 films show high first cycle electrochemical capacities of ∼ 1400 mAh/g, but the capacity rapidly degrades with charge/discharge cycling. We also fabricated core/shell MWCNT/RuO2 heterostructured 3D electrodes, which show a 50× increase in the areal capacity over their planar counterparts, with an areal lithium capacity of 1.6 mAh/cm(2).


Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.
The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.


Introduction to the Special Issue on Multisensory Research Forum (IMRF 2016, Suzhou).
This editorial introduction briefly summarized the general information and keynote topics of 17th International Multisensory Research Forum (IMRF 2016), which was held in Suzhou, China on June 15-18, 2016. In this IMRF2016 Multisensory Research special issue, seven papers have been collected. Some topics represent mainstream, traditional studies, while others show a range of multidisciplinary approaches. We categorized the main topics in this issue to four aspects: expertise in multisensory timing, neuronal signatures underlying cross-modal correspondence, coupling between perception and action, and lastly, a revisit of the principles for multisensory segregation and integration.


Apotirucallane and tirucallane triterpenoids from Cedrela sinensis.
Nine new triterpenoids, 1-9, were isolated from the cortex of Cedrela sinensis (Meliaceae), together with six known compounds, sapelin E acetate, grandifoliolenone, azadirone, bourjotinolone A, piscidinol A, and hispidol B. The structures of 1-9 were determined by the 2D NMR experiments, chemical methods, and X-ray crystallography.


Modulation of prostaglandin E2 synthesis in rabbit synoviocytes.
Prostaglandin E2 (PGE2) production by rabbit synoviocytes was markedly stimulated by hydroxyapatite only after a 60-minute delay. Release of 3H-arachidonic acid (C20:4) and 3H-PGE2 from cells with phospholipids that were prelabeled with 3H-C20:4 did not occur in parallel. At 240 minutes, phospholipase activity in sonicated cell suspensions had increased only 38%, while cyclooxygenase activity had doubled (109%). This doubling, as well as the production of synoviocyte PGE2, was prevented by inhibiting the synthesis of protein. Cyclooxygenase is an inducible enzyme, and as such, it is a rate-controlling step in PGE2 production.


Biomechanical Features of Backstroke to Breaststroke Transition Techniques in Age-Group Swimmers.
This study aimed to identify the biomechanical features of backstroke to breaststroke transition techniques (open, somersault, bucket, and crossover) in age-group swimmers. Eighteen preadolescent swimmers (12.2 ± 0.4 years old and 3-4 Tanner stages) underwent 4 weeks of systematic contextual interference training, comprising 16 sessions (40 min·session-1). Soon after, experimental testing was conducted where swimmers randomly performed 12 × 15 m maximal turns (composed of 7.5 m turn-in and 7.5 m turn-out of the wall segments), three in each transition technique. Kinematical, kinetic, and hydrodynamic variables were assessed with a dual-media motion capture system (12 land and 11 underwater cameras), triaxial underwater force plates, and inverse dynamics. Variables were grouped in turn-in (approach and rotation) and turn-out (wall contact, gliding, and pull-out) phases, with factor analysis used to select the variables entering on multiple regressions. For the turn-in phase, 86, 77, 89, and 87% of the variance for open, somersault, bucket, and crossover turning techniques, respectively, was accounted by the 7.5 and 2.5 m times, mean stroke length, and rotation time. For the turn-out phase, first gliding distance and time, second gliding depth, turn-out time, and dominating peak_Z push-off force accounted for 93% in open turn, while wall contact time, first gliding distance, breakout distance and time, turn-out time, dominating peak_Y push-off force, and second gliding drag coefficient accounted for 92% in a somersault turn. The foot plant index, push-off velocity, second gliding distance, and turn-out time accounted for 92% in bucket turn while breakout and turn-out time, non-dominating peak_Y and peak_Z push-off force, first and second gliding drag force and second gliding drag coefficient accounted for 90% in crossover turn, respectively. The findings in this study were novel and provided relevant biomechanical contribution, focusing on the key kinematic-temporal determinant during turn-in, rotation, and push-off efficacy, and the kinetic and hydrodynamic during turn-out, which would lead to improved backstroke to breaststroke transition techniques in 11-13 years-old age-group swimmers.


Natural history of mild subclinical hypothyroidism in a middle-aged and elderly Chinese population: a prospective study.
Subclinical hypothyroidism (SCH) has a high global prevalence. Most SCH patients have mild cases (thyrotropin ≤10 mIU/L). Treatment recommendations for mild SCH are controversial, which raises concerns about the natural history of mild SCH. We aimed to clarify the natural history of mild SCH. This is a prospective population-based study. We measured thyroid function in 11,000 participants in the REACTION study and followed 505 newly diagnosed mild SCH patients aged 40-years or older between 2011 and 2014. Logistic regression analysis was used to seek baseline parameters associated with the natural outcomes of mild SCH. Among 505 mild SCH patients, 221 (43.8%) had persistent SCH, 251 (49.7%) reverted to euthyroidism, and 17 (3.4%) progressed to overt hypothyroidism (OH). Patients with higher baseline total cholesterol (TC, between 201.0-240.0 mg/dL or >240.0 mg/dL vs. <201.0 mg/dL, p = 0.048 and 0.006, respectively) or positive thyroid peroxidase antibodies (TPOAb, p = 0.009) had higher risks of progression to OH, while those with higher baseline creatinine (CR, between 0.71-0.80 mg/dL or >0.80 mg/dL vs. ≤0.65 mg/dL, p = 0.031 and 0.004, respectively), higher baseline thyrotropin (≥7 mIU/L, p < 0.001) or older (>60 years vs. ≤50 years, p = 0.012) had lower odds of reverting to euthyroidism. In conclusion, TPOAb and TC seem to be more important predictors of progression to OH than initial thyrotropin, whereas high baseline thyrotropin or CR were negative correlated with reversion to euthyroidism. The prognostic value of TC and CR in mild SCH should be considered.


Spanish Validation and Scoring of the Internet Gaming Disorder Scale - Short-Form (IGDS9-SF).
Since the inclusion of the Internet Gaming Disorder (IGD) in the Diagnostic and statistical manual of mental disorders (5th ed.) (DSM-5), the Internet Gaming Disorder Scale-Short Form (IGDS9-SF), a short nine items test, has become one of the most used standardized instruments for its psychometric evaluation. This study presents a validation and psychometric evaluation of the Spanish version of the IGDS9-SF. A sample of 2173 videogame players between 12 and 22 years old, comprising both genders, was employed, achieved with a randomized selection process from educational institutions in the city of Madrid. Participants completed the adapted version of the IGDS9-SF, the General Health Questionnaire (GHQ-12) and a negative cognitions scale associated with videogame use, as well as sociodemographic data and frequency of videogame play. A unifactorial structure with sufficient reliability and internal consistency was found through exploratory and confirmatory analyses. In addition, the instrument was found to have good construct validity; the scoring of the IGDS9-SF were found to show a positive association with gaming frequency, with general health problems, and to a greater extent, with problematic cognitions with regard to videogames. Factorial invariance was found concerning the age of participants. However, even though the factorial structure was consistent across genders, neither metric nor scalar invariance were found; for this reason, we present a scale for the whole sample and a different one for gender. These results suggest that this Spanish version of the IGDS9-SF is a reliable and valid instrument, useful to evaluate the severity of IGD in Spanish students, and we provide a scoring scale for measurement purposes.


Psoriasis in childhood: effective strategies to improve treatment adherence.
Psoriasis is a relatively common chronic inflammatory skin disease in children for which there is no cure. Most children have mild disease that can be managed with topical therapy as opposed to phototherapy or systemic therapy. Despite the mild presentation of psoriasis in most children, the disease can have a significant impact on quality of life due to the need for ongoing treatment, the frequently visible nature of the cutaneous manifestations, and the social stigma that is associated with psoriasis. Adherence to treatment, in particular topical therapy, is often poor in adults and compromises response to therapy and medical provider management strategies. Multiple factors that may contribute to nonadherence in adults with psoriasis have been identified, including lack of education on the disease and expectations for management, issues related to ease of use and acceptability of topical medications, and anxiety regarding possible medication side effects. There is currently no published data on adherence in the pediatric psoriasis population; however, poor adherence is often suspected when patients fail to respond to appropriate therapy. General strategies used to assess adherence in other pediatric disease populations can be applied to children with psoriasis, and interventions that reflect experience in other chronic dermatologic disorders such as atopic dermatitis may also be helpful for medical providers caring for children with psoriasis.


High-Density Lipoprotein Function and Dysfunction in Health and Disease.
High-density lipoprotein cholesterol (HDL-c) has long been referred to as 'good cholesterol' due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled trials have found no evidence of a cardiovascular protective effect when HDL-c levels are raised. Instead, focus has switched to the functional properties of the HDL particle. Evidence suggests that both the composition and function of HDL may be significantly altered in the context of an inflammatory milieu, transforming the particle from a vasoprotective anti-atherogenic particle to a noxious pro-atherogenic equivalent. This review will summarise evidence relating HDL to CVD risk, explore recent evidence characterising changes in the composition and function of HDL that may occur in chronic inflammatory diseases, and discuss the potential for future HDL-modifying therapeutic interventions.


Patient characteristics for outpatient acupuncture in Beijing, China.
This study quantifies and compares patient characteristics in outpatient acupuncture. Prospective primary source evidence was gathered at two prominent outpatient acupuncture clinics in Beijing, China (n = 563, n = 233). The most common condition was Bell's palsy, which represented 20.6% and 25.3% of total cases at the two clinics, respectively. The second most common condition was cerebrovascular accident (CVA) rehabilitation. These treatments represented 11.9% and 12.0% of treatments at the two clinics, respectively. Other trends at the clinics included the following: (1) neurologic complaints predominated; (2) doctors see a large number of patients per day; (3) the majority of patients overall were female; while (4) the majority of patients treated for CVAs rehabilitation were male. As cultural and socioeconomic differences in perceptions of acupuncture exist between peoples of different countries, this study also compared patient main complaints in China to available data on acupuncture patients seen in other parts of China, Germany, the United Kingdom, Australia, and the United States. Except for the German clinic data, Western clinic acupuncturists saw more musculoskeletal complaints compared to China, where neurologic complaints predominated. Another significant difference between Asian and Western clinics was the number of patients seen per hour. While acupuncturists were reported to see 1.2 patients per hour in U. S. clinics, acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per hour, respectively. The main complaints seen in acupuncture outpatient clinics throughout the world likely result from a combination of inherent disease prevalence as well as patients' attitudes toward what acupuncture can treat successfully.


Retinoblastoma protein expression in endometrial hyperplasia and carcinoma.
The retinoblastoma (RB) gene was the first defined tumor suppressor gene. While originally described in retinoblastoma, more recently alterations in RB have been described in a number of other human neoplasms and there has been a suggestion that alteration of RB may play a significant role in the development of endometrial carcinoma. We examined RB protein expression by immunohistochemistry in a series of cases including normal endometrium, endometrial hyperplasia, and endometrial carcinoma. A relatively homogeneous pattern of staining was observed in proliferative endometrium, while weak or absent reactivity was noted in secretory endometrium. A heterogeneous pattern of reactivity was observed in 10/10 cases of hyperplasia, 66/70 cases of endometrial adenocarcinoma, and 7/7 cases of uterine carcinosarcoma. An altered pattern of reactivity was observed in the remaining 4/70 cases of adenocarcinoma. All of the cases with altered reactivity were high grade neoplasms. We conclude that alteration of RB protein expression is uncommon in endometrial adenocarcinoma and when it does occur, it may represent a late event in carcinogenesis.


[Endoscopic assistance in surgery of cerebellopontine angle tumors].
During the period of 2010-2012, 33 patients with cerebellopontine angle tumors were operated on at the Burdenko Neurosurgical Institute (Moscow, Russia) using different types of endoscopic assistance. All patients were operated on via the retrosigmoid suboccipital approach in semi-sitting and prone positions. 30° and 70° endoscopes were used during the surgery. Endoscopic assistance allowed us to increase the completeness of tumor removal and to reduce the risk of postoperative complications by retaining the anatomic integrity of cranial nerves and vascular structures in the base of the posterior cranial fossa. These benefits made it possible to maintain and improve quality of life in patients with CPA tumors in the postoperative period.


Audit-Based Quality Validation of the Japan Cardiovascular Surgery Database.
The Japan Cardiovascular Surgery Database (JCVSD) is a nationwide registry of patients undergoing cardiovascular surgery in Japan. To investigate and improve data quality, we have been conducting on-site institutional audits since 2004. This study aimed to investigate the accuracy of the registered data by comparing it to site visit data.Methods and Results:The subjects of this study were the 95 facilities at which a site visit was conducted. The case registration accuracy was 98.74%. Furthermore, we confirmed high data input accuracy of >90% for almost all fields. Approximately 99% of cases had been correctly entered for diabetes, aortic stenosis, and mortality. We also discovered which fields were more likely to be incorrectly captured and the causes thereof, as well as problems regarding some definitions and the input system itself. We were able to confirm high registration accuracy in the JCVSD. Appropriately resourced, focused site visits as part of a national audit are capable of accurate data collection on which continual nationwide quality control can be based. Continued work and development to further improve the quality of the database are mandatory to maintain a high standard of cardiovascular surgery in Japan.


Population-based epidemiology and microbiology of community-onset bloodstream infections.
Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide. While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity. Community-onset BSIs are those that occur in outpatients or are first identified <48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases. The most common causes of community-onset BSI include Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrobial-resistant organisms, including methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase/metallo-β-lactamase/carbapenemase-producing Enterobacteriaceae, have emerged as important etiologies of community-onset BSI.


Identification of Covalent Binding Sites Targeting Cysteines Based on Computational Approaches.
Covalent drugs have attracted increasing attention in recent years due to good inhibitory activity and selectivity. Targeting noncatalytic cysteines with irreversible inhibitors is a powerful approach for enhancing pharmacological potency and selectivity because cysteines can form covalent bonds with inhibitors through their nucleophilic thiol groups. However, most human kinases have multiple noncatalytic cysteines within the active site; to accurately predict which cysteine is most likely to form covalent bonds is of great importance but remains a challenge when designing irreversible inhibitors. In this work, FTMap was first applied to check its ability in predicting covalent binding site defined as the region where covalent bonds are formed between cysteines and irreversible inhibitors. Results show that it has excellent performance in detecting the hot spots within the binding pocket, and its hydrogen bond interaction frequency analysis could give us some interesting instructions for identification of covalent binding cysteines. Furthermore, we proposed a simple but useful covalent fragment probing approach and showed that it successfully predicted the covalent binding site of seven targets. By adopting a distance-based method, we observed that the closer the nucleophiles of covalent warheads are to the thiol group of a cysteine, the higher the possibility that a cysteine is prone to form a covalent bond. We believe that the combination of FTMap and our distance-based covalent fragment probing method can become a useful tool in detecting the covalent binding site of these targets.


Effect of glycerol on a diacetone acrylamide-based holographic photopolymer material.
The composition of the low-toxicity, environmentally compatible diacetone acrylamide (DA) photopolymer has been modified with the inclusion of different additives. The addition of glycerol to the photopolymer composition is described. Results show that the incorporation of glycerol results in a uniform maximum refractive-index modulation for recording intensities in the range of 1-20 mW/cm(2). This may be attributed to glycerol's nature as a plasticizer, which allows for faster diffusion of an unreacted monomer within the grating during holographic recording. An optimum recording intensity of 0.5 mW/cm(2) is observed for exposure energies of 20-60 mW/cm(2). The modified photopolymer achieves a refractive-index modulation of 2.2×10(-3), with diffraction efficiencies up to 90% in 100 μm layers. Glycerol has also shown to reduce the rate of photobleaching of the DA photopolymer. This is possibly due to more prevalent inhibition effects caused by increased oxygenation of the photopolymer layers. The stability of the photopolymer samples is also improved with the addition of glycerol.


Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study.
Most patients with advanced head and neck cancer receiving chemoradiotherapy need tube feeding for at least some weeks. For these periods gastrostomy tubes have advantages over nasogastric tubes. Tube feeding may start earlier and thus loss of weight may be limited if the gastrostomy tube already is in place. The objective of this study is to analyse the results of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement and early tube feeding. Retrospective chart review. Multidisciplinary head and neck oncology team in a general hospital. Fifty consecutive patients with unresectable stage III and IV head and neck cancer treated with concurrent chemoradiotherapy. In all patients prophylactic PEG placement was performed. Tube feeding was initiated if food-intake became insufficient or loss of weight occurred. Loss of weight during treatment, complication rate, PEG duration. The mean loss of weight during treatment for all patients was only 2.8%. One complication of tube placement occurred: a colon perforation, treated successfully by surgery. The median duration of the PEG was 178 days. Three of the 17 patients (18%) with no evidence of disease (NED) still had a PEG at their last follow-up visit. Of the 26 patients who died of their cancer, 13 used the PEG until death. Loss of weight was limited after prophylactic gastrostomy placement and early tube feeding. Moreover, the complication rate was low. In 82% of the NED patients the PEG could eventually be removed.


Caries prevalence of 11.5 year-olds between 1989 and 2001 in a province of North-Eastern Greece.
To compare cross-sectional caries prevalence data of 11.5 year old children over a 13 year period (1989-2001) and to evaluate the maximum effect of the applied preventive programme (sealants to 1st molars and 6-year health education) on DMFT values during the last five years. Using the records of a Public Health Centre (PHC) in NE Greece, a number (153-250) of children aged 11.5-years were selected from each calendar year, constituting 11 study groups (totalling 2,217 children), stratified by area of residency. Annual oral health education sessions provided in 1990, a year after the PHC was established. Light-cured fissure sealants were systematically mass introduced in 1996. The same dentist completed all DMFT records in the dental clinic during the children's routine visits. DMFT was analysed using two Poisson and two Binomial models for both data from all years, and for the last five years. The models had as factors: "Time" (year of examination of the study group), "Residency" (semi urban, rural lowland, rural highland), number of "Sealed 1st molars" and "Sealed posterior teeth". All the factors were highly statistically significant (p<0.001). Dental health was found to be good (DMFT=0), improving progressively year by year (range 12-50%). The mean DMFT decreased steadily from 4.5 (in 1989) to 1.81 (in 2001). The Significant Caries index was almost halved (from 8.08 to 4.23). An important improvement in the caries status of 11.5 year-olds since 1989 has been demonstrated, irrespective of the residency. The systematic application of fissure sealants to all 1st molars, parallel to the cumulative effect of the 6-year health education programme per child, played a significant role in reducing disparities in disease prevalence, despite the difficulty of improving rates of decline when the caries levels are relatively low.


Application of the method of thermal denaturation for investigation of alpha-chymotrypsin adducts with poly.
The thermostability of conjugates, non-covalent complexes and mixtures of alpha-chymotrypsin (alpha-ChT) with poly(alkylene oxides)--poly(ethylene glycol) (PEG) with molecular mass of 1.9 kD and diblock copolymers of ethylene and propylene oxides (proxanols)--has been investigated. It was shown that the addition of PEG in concentration up to 2 wt. % to the solution of alpha-ChT did not affect the rate of the enzyme thermoinactivation. Meanwhile the addition of proxanol in the same concentration resulted in twofold decrease in the rate constant for the slow inactivation step, k2. Even more pronounced decrease in the thermoinactivation rate was observed for alpha-ChT--proxanol complexes obtained by heating or under the action of high pressure. The general tendency in the behavior of complexes of both types was the decrease in the k2 constant as the temperature or pressure used for complex preparation increased. The highest stabilizing effect was observed for complex obtained by heating up to 52 degreesC and containing maximal number of polymer chains (molar ratio proxanol/alpha-ChT was 10). For this complex fourfold decrease in the k2 value was observed. Covalent attachment of PEG or proxanol to enzyme gives maximal stabilizing effect with up to tenfold decrease in the k2 value. The investigation of the thermal denaturation kinetics of alpha-ChT and its adducts with poly(alkylene oxides) by means of fluorescence spectroscopy has shown that the presence of polymer chains practically does not affect the rate of protein denaturation registered by the decrease in the intensity of protein fluorescence. The polymer chains, probably, diminish the rate of melting of the active site-containing region of the protein molecule. At the same time, the overall denaturation rate is independent of the presence of polymer chains in the vicinity of the protein globule.


Myocardial stress and autophagy: mechanisms and potential therapies.
Autophagy is a ubiquitous cellular catabolic process responsive to energy stress. Research over the past decade has revealed that cardiomyocyte autophagy is a prominent homeostatic pathway, important in adaptation to altered myocardial metabolic demand. The cellular machinery of autophagy involves targeted direction of macromolecules and organelles for lysosomal degradation. Activation of autophagy has been identified as cardioprotective in some settings (that is, ischaemia and ischaemic preconditioning). In other situations, sustained autophagy has been linked with cardiopathology (for example, sustained pressure overload and heart failure). Perturbation of autophagy in diabetic cardiomyopathy has also been observed and is associated with both adaptive and maladaptive responses to stress. Emerging research findings indicate that various forms of selective autophagy operate in parallel to manage various types of catabolic cellular cargo including mitochondria, large proteins, glycogen, and stored lipids. In this Review, induction of autophagy associated with cardiac benefit or detriment is considered. The various static and dynamic approaches used to measure autophagy are critiqued, and current inconsistencies in the understanding of autophagy regulation in the heart are highlighted. The prospects for pharmacological intervention to achieve therapeutic manipulation of autophagic processes are also discussed.


Clinicopathological Patterns of Malignant Solid Tumors in Adult Patients: A Hospital-Based Study From Bangladesh.
Solid malignant tumors are abnormal masses of tissue that usually do not contain any cysts or liquid areas. The causation of these tumors is multifactorial, and the disease process differs at different sites. This study aims to determine the clinicopathological patterns of malignant solid tumors in adult patients admitted into the department of internal medicine of a tertiary care hospital in Bangladesh. This cross-sectional study was conducted between January 2018 and June 2018 at the Department of Medicine, Dhaka Medical College Hospital, Bangladesh. We recorded the complete socio-demographic characteristics, clinical patterns, and pathological characteristics of malignant solid tumors in adult patients. A total of 100 patients with confirmed malignant solid tumors were included in our study. The mean age of the patients was 47.5 years (SD: ±4.20); most of them (27%) were between 58 and 67 years of age. Male patients constitute 59% of the total study sample. Most of the patients were of the middle socio-economic class (59%) and most of them (61%) were nonsmokers. Among the patient diagnoses, 19% had lung cancer, 29.27% had breast cancer, and in 14%, lymphoma (tumor arising from the lymphatic system) was the common solid tumor. Lung cancer was found to be the most common form of cancer in males. Additionally, the majority of those diagnosed with lung cancer smoked. Breast cancer was found to be the most common type of cancer in females. This study reflects that solid malignant tumors can affect any socio-economic class of people. Based on findings in our study as well as others, prevention efforts should focus on the reduction in tobacco use and the incorporation of other lifestyle changes, such as diet modification and exercise. Additionally, the incorporation of economic factors and how they affect cancer presentation in different contexts is crucial.


Diagnostic Accuracy of Noninvasive Fibrosis Scores in a Population of Individuals With a Low Prevalence of Fibrosis.
Noninvasive scoring systems for fibrosis are increasingly used in the clinic and in research because of their ease of use, accessibility, and low cost. However, test performance characteristics were established in groups of patients with a high prevalence of advanced fibrosis; little is known about diagnostic accuracy in low-risk populations. In a cross-sectional study, 922 members of a general ambulatory population in Hong Kong (randomly selected; 18-70 years old) underwent clinical assessment from May 2008 through December 2010. All participants completed a standard questionnaire that collected information on age, sex, and history of smoking and alcohol use. Results of fasting blood tests and transient elastography were used as the reference standard to identify patients with advanced fibrosis. We assessed performance characteristics of 3 noninvasive fibrosis scoring systems: the nonalcoholic fatty liver disease fibrosis scoring system, the Fibrosis-4 scoring system, and aspartate transaminase to platelet ratio index, using standard thresholds. To calculate diagnostic test characteristics, we constructed a 2-by-2 table with the presence or absence of advanced fibrosis according to the transient elastography reading against the presence or absence of advanced fibrosis according to the scoring systems. Area under the receiver operating curve was calculated to assess overall diagnostic accuracy. Of the 922 individuals evaluated by transient elastography, 749 had a valid reading and 15 had advanced fibrosis (2%). The specificity of noninvasive scores in detection of advanced fibrosis approximated 100% (95% confidence interval [CI], 99%-100%), with a negative predictive value of 98% (95% CI, 97%-99%) for all systems. However, the scoring systems detected fibrosis with a low level of sensitivity, ranging from 7% (95% CI, 0%-32%) to 13% (95% CI, 2%-40%). Positive predictive values ranged from 50% (95% CI, 7%-93%) to 67% (95% CI, 9%-99%). Their negative likelihood ratios ranged from 0.87 (95% CI, 0.71%-1.06%) to 0.93 (95% CI, 0.82%-1.07%); positive likelihood ratios were uninformative because of the small number of people with positive scores. In low-risk populations, negative results from noninvasive scoring systems reliably exclude advanced fibrosis, without requirements for further tests. Positive test results are often a false-positive result and should prompt further testing.


Topographic cues reveal filopodia-mediated cell locomotion in 3D microenvironment.
In cell-material interactions, the formation and functioning of filopodia have been demonstrated to be very sensitive to topographic cues. However, substrate-exploring functions of filopodia in a 3D microenvironment remain elusive. In this study, the silk fibroin film with a micropillar structure was prepared to reveal a filopodial-mediated cell response to 3D topographic cues. The micropillars provided a confined space for cell spreading by a simplified 3D structure, allowing initial cells to settle on the bottom of substrates rather than on the top of micropillars. Shortly after cell adhesion, the authors describe how cells transform from a filopodia-rich spherical cell state to a lamellipodia-dominated state that enables cell to climb along micropillars and spread on the top of the micropillars. The authors found that filopodia not only served as sensors for pathfinding but also provided nucleation scaffolds for the formation and orientation of minilamellipodia on the micropillar substrate. On the route of long filopodial extension following micropillars, all three functional filopodial adhesions have the ability to form veil-like minilamellipodium, simply by tethering the filopodium to the micropillars. Stable filopodia contacts consistently stimulated the local protrusion of a lamellipodium, which ultimately steered cell migration. Their results suggest the filopodia-mediated cell locomotion in the 3D microenvironment using a filopodia-to-minilamellipodium transformation mechanism.


Physical activity, health-related quality of life, and adjuvant endocrine therapy-related symptoms in women with hormone receptor-positive breast cancer.
Physical activity (PA) is recommended for women with breast cancer (BC); however, data are sparse on the association of PA with quality of life (QOL) and patient-reported symptoms for women on adjuvant endocrine therapy (AET). Women with hormone receptor-positive BC who were taking AET completed standardized surveys about their health-related QOL, AET-related symptoms, and levels of PA using validated measures. A Wald chi-square test and an analysis of variance were used to assess associations with PA and independent variables. Generalized linear regression analyses assessed associations between PA, QOL, and AET-related symptoms. The analytic cohort included 485 Black and White women. Black race, a high body mass index (BMI), and being on aromatase inhibitors (vs tamoxifen) were associated with lower PA in a bivariate analysis. In a multivariate analysis, lower self-reported PA was associated with a high BMI (P = .02) and chemotherapy uptake (P = .006). Better health-related QOL (P = .01), less severe overall AET-related symptoms (P = .02), and less severe gynecological symptoms (P = .03) were associated with increasing levels of moderate PA. Among women taking AET, moderate levels of PA may be associated with fewer medication-related symptoms and overall better ratings of health-related QOL. Because of the low levels of PA observed in the sample overall and particularly for Black women, identifying successful strategies to promote PA are needed.


Effects of nitroxides on the magnetic field and temperature dependence of 1/T1 of solvent water protons.
We report a study of the longitudinal NMRD profiles (proton longitudinal relaxation rates as a function of field strength) over a broad range of magnetic field (0.01 to 50 MHz proton Larmor frequency) and temperature (-9.6 to 37 degrees C) for aqueous solutions of (i) a fatty acid-nitroxide/albumin complex and (ii) 10 low molecular weight nitroxides. Analysis of the NMRD profile for the fatty acid-nitroxide/albumin complex provides a lower bound estimate for the rotational correlation time of the complex, which permits the calculation of an upper bound on the inner sphere contribution to relaxation of the uncomplexed nitroxides. Inner sphere processes, ostensibly due to water molecules hydrogen bonded to the nitroxide moiety, dominate the relaxation effects of the slowly rotating macromolecular nitroxide/albumin complex. By extrapolation, the contribution of these inner sphere processes are negligible for rapidly tumbling nitroxides free in solution, which affect solvent proton relaxation almost entirely through outer sphere processes (i.e., translational diffusion). A comparison of the relaxation data for aqueous solutions of the uncomplexed nitroxides with the theory of outer sphere relaxation of J.H. Freed (J. Chem. Phys. 68, 4034 (1978] yields values for the distance of closest approach of the water and nitroxide molecules, as well as for their relative diffusion constants, at five different temperatures. Our results indicate that the rather modest relaxivities of aqueous solutions of nitroxides increase substantially with increased solvent viscosity and with protein binding, supporting the potential utility of nitroxides for enhancement of contrast in nuclear magnetic resonance images.


Serum cholesterol levels as a measure of frailty in elderly patients.
The authors evaluated the association between serum cholesterol levels and social, clinical, and functional characteristics in 637 elderly hospitalized patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy). Patients consecutively admitted to the GERU during an 18-month period underwent a multidimensional evaluation including information on demographics, cognitive status, physical health (number of chronic diseases and administered drugs), functional disability, and nutritional status. Mean cholesterol levels were significantly lower in men; persons living with others; older individuals; and individuals with cognitive impairment, poorer somatic health, higher disability, and a higher level of malnutrition. Lower serum cholesterol levels may be considered an independent hematologic marker of frailty in elderly hospitalized patients.


Mold filling of titanium alloys in two different wedge-shaped molds.
Pure titanium and titanium alloys are potential materials for the fabrication of cast dental appliances. One important factor in producing sound castings is the capacity of the metal to fill the mold. This study used a wedge-shaped mold to compare the mold filling of titanium with that of conventional dental casting alloys. The metals used were CP Ti, Ti-6Al-7Nb, Ti-6Al-4V, Ti with 1 and 4wt% Cu and ADA Type III gold alloy and an Ni-Cr alloy. The castings were cut into four pieces parallel to the triangular surface. Mold filling was evaluated as the distance between the tip of the cast wedge and theoretical tip of the triangle. The mold filling of the gold alloy was superior compared to all the metals tested, while the mold filling of the Ni-Cr alloy was the worst. There were no statistical differences at the 30 degrees marginal angle for all the cast titanium metals. At the sharper 15 degrees angle, CP Ti and Ti-6Al-7Nb was superior to both the Ti-Cu alloys. Although the mold filling of titanium was inferior compared to the gold alloy, the data justify the use of titanium for the production of dental appliances.


A simpler structure for local spatial channels revealed by sustained perifoveal stimuli.
A new evaluation of the local structure of spatial channels with sustained stimuli in perifoveal retina employs the masking sensitivity approach to minimize analytic assumptions. The stimuli were designed to address the range of channel tunings of the predominantly sustained response system in the near periphery. Under these conditions, the range of identifiable channels spanned a narrow range of spatial frequencies, from roughly 2-8 cpd at 2° eccentricity to 1-4 cpd at 8° eccentricity. The analysis showed that there are no sustained channels tuned below 2 cpd for the central visual field. This two-octave range of channel tuning is much narrower than is conventionally assumed. For local sustained stimuli, human peripheral spatial processing therefore appears to be based on a simpler channel structure than is often supposed.