Sustainable food consumption. Product choice or curtailment?
Food consumption is an important factor in shaping the sustainability of our food supply. The present paper empirically explores different types of sustainable food behaviors. A distinction between sustainable product choices and curtailment behavior has been investigated empirically and predictors of the two types of behavior have been identified. Respondents were classified into four segments based on their sustainable food behaviors: unsustainers, curtailers, product-oriented consumers, and sustainers. Significant differences between the segments were found with regard to food choice motives, personal and social norms, food involvement, subjective knowledge on sustainable food, ability to judge how sustainably a product has been produced and socio-demographics. It is concluded that distinguishing between behavioral strategies toward sustainable food consumption is important as consumer segments can be identified that differ both in their level of sustainable food consumption and in the type of behavior they employ.


Effects of low-flow sevoflurane anesthesia on renal function: comparison with high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.
The safety of low-flow sevoflurane anesthesia, during which CF2=C(CF3)-O-CH2F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia. Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase. The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia. The only difference between the low-flow and high-flow sevoflurane groups was compound A formation, and postanesthesia laboratory data showed no significant effects of compound A formation during sevoflurane anesthesia on renal function. No significant effects on renal function were observed in either the low-flow or high-flow sevoflurane groups compared with the low-flow isoflurane group.


Comprehensive profiling of cartilage extracellular matrix formation and maturation using sequential extraction and label-free quantitative proteomics.
Articular cartilage is indispensable for joint function but has limited capacity for self-repair. Engineering of neocartilage in vitro is therefore a major target for autologous cartilage repair in arthritis. Previous analysis of neocartilage has targeted cellular organization and specific molecular components. However, the complexity of extracellular matrix (ECM) development in neocartilage has not been investigated by proteomics. To redress this, we developed a mouse neocartilage culture system that produces a cartilaginous ECM. Differential analysis of the tissue proteome of 3-week neocartilage and 3-day postnatal mouse cartilage using solubility-based protein fractionation targeted components involved in neocartilage development, including ECM maturation. Initially, SDS-PAGE analysis of sequential extracts revealed the transition in protein solubility from a high proportion of readily soluble (NaCl-extracted) proteins in juvenile cartilage to a high proportion of poorly soluble (guanidine hydrochloride-extracted) proteins in neocartilage. Label-free quantitative mass spectrometry (LTQ-Orbitrap) and statistical analysis were then used to filter three significant protein groups: proteins enriched according to extraction condition, proteins differentially abundant between juvenile cartilage and neocartilage, and proteins with differential solubility properties between the two tissue types. Classification of proteins differentially abundant between NaCl and guanidine hydrochloride extracts (n = 403) using bioinformatics revealed effective partitioning of readily soluble components from subunits of larger protein complexes. Proteins significantly enriched in neocartilage (n = 78) included proteins previously not reported or with unknown function in cartilage (integrin-binding protein DEL1; coiled-coil domain-containing protein 80; emilin-1 and pigment epithelium derived factor). Proteins with differential extractability between juvenile cartilage and neocartilage included ECM components (nidogen-2, perlecan, collagen VI, matrilin-3, tenascin and thrombospondin-1), and the relationship between protein extractability and ECM ultrastructural organization was supported by electron microscopy. Additionally, one guanidine extract-specific neocartilage protein, protease nexin-1, was confirmed by immunohistochemistry as a novel component of developing articular cartilage in vivo. The extraction profile and matrix-associated immunostaining implicates protease nexin-1 in cartilage development in vitro and in vivo.


Historical records of orchid bees (Apidae: Euglossini) in Belém Endemism Center: species list of 92 years sampling.
The distribution of most species occurs in delimited regions with unique characteristics called "centers of endemism". In Eastern Amazon is located the Belém Endemism Center (BEC), one of the most intensely deforested in Brazilian Amazon. Here, we show information about orchid bee assemblages based on historical records from entomological collections. For each species, we calculated occurrence frequency and dominance, and we classified them in 3 statuses: common, intermediate or rare species. Curves of observed and estimated richness were built, based on Jackknife estimator. We found 1,257 specimens from 56 species, constituting records from 1917 to 2009, and one species is a new record for BEC. Higher number of specimens and species was concentrated in a few locations and surveys increased from the 70's. The results suggest a high richness of orchid bees in the BEC, although this scenario is far from what is expected for the entire area. The high occurrence of rare species may be related to their low representativeness in the collections, and the proximity between the areas had favored samplings. Even so, the species list and the conservation status presented here may be useful information in studies comparing past and current orchid bee fauna, and, allied to data on bees' responses to land use changes occurred in BEC over the years, can fit as a basis for defining priority areas for conservation.


Immediate versus deferred delivery of the preterm baby with suspected fetal compromise for improving outcomes.
Immediate delivery of the preterm fetus with suspected compromise may decrease the risk of damage due to intrauterine hypoxia. However, it may also increase the risks of prematurity. To assess the effects of immediate versus deferred delivery of preterm babies with suspected fetal compromise on neonatal, maternal and long-term outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 February 2012). Randomised trials comparing a policy of immediate delivery with deferred delivery or expectant management in preterm fetuses with suspected in utero compromise. Quasi-randomised trials and trials employing a cluster-randomised design were eligible for inclusion but none were identified. Two review authors independently evaluated trials for inclusion into the review. Two review authors assessed trial quality and extracted data. Data were checked for accuracy. We included one trial of 548 women (588 babies) in the review. There was no difference in the primary outcomes of extended perinatal mortality (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.67 to 2.04) or the composite outcome of death or disability at or after two years (RR 1.22, 95% CI 0.85 to 1.75) with immediate delivery compared to deferred delivery. More babies in the immediate delivery group were ventilated for more than 24 hours (RR 1.54, 95% CI 1.20 to 1.97). There were no differences between the immediate delivery and deferred delivery groups in any other individual neonatal morbidity or markers of neonatal morbidity (cord pH less than 7.00, Apgar less than seven at five minutes, convulsions, interventricular haemorrhage or germinal matrix haemorrhage, necrotising enterocolitis and periventricular leucomalacia or ventriculomegaly).More children in the immediate delivery group had cerebral palsy at or after two years of age (RR 5.88, 95% CI 1.33 to 26.02). There were, however, no differences in neurodevelopment impairment at or after two years (RR 1.72, 95% CI 0.86 to 3.41) or death or disability in childhood (six to 13 years of age) (RR 0.82, 95% CI 0.48 to 1.40). More women in the immediate delivery group had caesarean delivery than in the deferred delivery group (RR 1.15, 95% CI 1.07 to 1.24). Data were not available on any other maternal outcomes. Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations to guide clinical practice. Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby. More research is needed to guide clinical practice.


Anabolic competence: Assessment and integration of the multimodality interventional approach in disease-related malnutrition.
Disease-related malnutrition (DRM) is a frequent clinical problem, characterized by loss of lean body mass and decreased function, including muscle function and immunocompetence. In DRM, nutritional intervention is necessary, but it has not consistently been shown to be sufficient. Other factors, for example, physical activity and hormonal or metabolic influencers of the internal milieu, are also important in the treatment of DRM. A prerequisite for successful treatment of DRM is the positive balance between anabolism and catabolism. The aim of this review was to approach DRM using this paradigm of anabolic competence, for conceptual and practical reasons. Anabolic competence is defined as "that state which optimally supports protein synthesis and lean body mass, global aspects of muscle and organ function, and immune response." Anabolic competence and interdisciplinary, multimodality interventions create a practical foundation to approach DRM in a proactive comprehensive way. Here, we describe the paradigm of anabolic competence, and its operationalization by measuring factors related to anabolic competence and suited for clinical management of patients with DRM.


Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network.
In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.


Enhancing action by sulfated hyaluronan on connexin-26, -32, and -43 gene expressions during the culture of normal human astrocytes.
Astrocyte proliferation is strictly controlled during development and in the adult nervous system. In this study, we examined the role of sulfated hyaluronan (SHya) in the proliferation and differentiation of normal human astrocytes (NHAs). Cells were cultured with different concentrations of SHya for 7 days, and the number of viable cells and the presence of neural cell-specific genes were determined to assess their proliferation and development, respectively. With SHya, cell proliferation increased nonsignificantly. Furthermore, remarkable enhancing action by SHya on connexin-26, -32, and -43 gene expressions were observed during the culture of NHAs. It has been suggested that a fraction of NHAs have neural precursor activity that gives rise to astrocytes themselves, oligodendrocytes, and neurons. Our results clearly demonstrated that the expression of specific genes for neural precursor cells, astrocytes, neurons, and oligodendrocytes was significantly increased to 50 mug/mL in SHya-treated cultures when compared with that of the control culture. These findings suggest that SHya plays an important role in the proliferation and differentiation of NHAs and in the production of a novel material for tissue engineering.


Maternal influences on fruit and vegetable consumption of schoolchildren: case study in Hong Kong.
This study investigated whether the consumption of fruit and vegetable by Chinese primary students in Hong Kong is associated with their mother's (1) nutrition knowledge on fruit and vegetables; (2) attitude towards healthy eating; and (3) fruit and vegetable consumption. Fourth- and fifth-grade students from 10 primary schools located in different districts, along with their mothers, were invited to each fill-in a questionnaire related to their diet intake. Accomplished questionnaires were matched and analysed. There were 1779 mother-child pairs who were successfully matched. Chi-square analysis revealed that students' fruit consumption is associated with their mother's (1) knowledge on fruit and vegetables (P = 0.006); (2) attitude towards healthy eating (P = 0.010); and (3) fruit consumption (P < 0.001). Students' vegetable consumption exhibited the same association with their mother's (1) knowledge (P < 0.001), (2) attitude towards healthy eating (P = 0.005), and (3) vegetable consumption (P < 0.001). Logistic regression showed that knowledge, attitude and dietary practice of mothers were independent factors associated with the consumption of fruit and vegetables by students and are not influenced by the level of education and household income. The results highlight the important role of parents in promoting fruit and vegetable consumption to primary students. It reaffirmed the importance of parent nutrition education in the formulation of a comprehensive health promotion strategy to school-aged children.


Etiology and management of diarrhoeal diseases in Karachi.
The incidence of diarrhoeal disease are very high in our population and bacterial etiology amounts to 43.55% of all cases. Pathogen such as Aeromonas hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica and Campylobacter are also present in significant numbers, they make up 50% of bacterial causes. All enteric pathogens can be easily isolated on commonly used media and could be precisely identified by simple biochemical tests.


Laparoscopic management of diaphragmatic endometriosis by three different approaches.
To report our three surgical approaches in the management of diaphragmatic endometriosis. Video article presenting laparoscopic surgical techniques, with and without robotic assistance. University hospital. Nulliparas with deep endometriosis associated with multiple endometriosis lesions of the diaphragm. Laparoscopic approach in women who present with small black-pigmented diaphragmatic lesions, with or without infiltration of the diaphragm, which are ablated using plasma energy. Robotic-assisted laparoscopic route in larger deep infiltrating implants, which are resected. To avoid phrenic nerve injury, robotic-assisted thoracoscopy is preferred in large lesions involving the central tendon of the diaphragm. The steps of each technique are emphasized. Surgical technique reports in anonymous patients are exempted from ethical approval by the Institutional Review Board. Seven patients have been managed by these procedures from July 2015 to March 2016. Patients' functional outcomes were uneventful, with no phrenic nerve palsy or residual chest and right shoulder pain. By combining resection and ablation techniques, the laparoscopy and thoracoscopy route, conventional and robotic-assisted minimally invasive approach, we offer a surgical strategy that is as conservative as possible, with an aim to limit postoperative adhesions between the liver and the diaphragm, and avoid diaphragmatic paralysis.


Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection.
TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of <0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.


[Clinicobiochemical and immunological assessment of polyoxidonium efficacy in the treatment of patients with chronic calculous pyelonephritis].
Of 59 patients with chronic calculous pyelonephritis (CCP) taking preparation therapy for extracorporeal lithotripsy, 29 patients received combined basic treatment (antibacterial drugs, phytotherapy, physiotherapy) plus polyoxidonium (a course of 10 intramuscular 6 mg injections each other day). The rest 30 patients (controls) received basic therapy alone. Polyoxidonium efficacy was assessed by the results of clinical, device and immunological investigations, content of the main phospholipid fractions and cholesterol in red cell membranes. The results of the tests show that polyoxidonium has anti-inflammatory and immunomodulating effects, exhibits activity of peroxidation processes, contributes to normalization of a lipid phase of cell membranes and can be recommended as a component of combined treatment of patients with chronic pyelonephritis and urolithiasis.


Fetofetal transfusion syndrome: do the neonatal criteria apply in utero?
Thirteen fetuses (five twin, one triplet) were compromised by fetofetal transfusion syndrome in six pregnancies, five in the mid trimester, and one in the third trimester. This diagnosis, which was suspected because of ultrasound findings of discordant growth, discordant amniotic fluid volumes, concordant external genitalia, and monochorial placentation, was confirmed postnatally in each. Nine fetuses underwent blood sampling to aid diagnosis and assessment of fetal wellbeing. In contrast to fetofetal transfusion syndrome investigated postnatally, a difference in haemoglobin concentration of 50 g/l or more in utero was found in only one pregnancy, which was near term, although all had fetal erythroblastaemia and a difference in weight of 20% or more. In vivo confirmation of shared circulation was achieved in two pregnancies by transfusing adult Rh negative red cells into the smaller fetus and then detecting them by Kleihauer testing in blood aspirated from the larger. Invasive procedures also yielded information on fetal blood gas measurements (acidaemia in four and hypoxaemia in six) and amniotic pressure (raised in two). We suggest that comparison of haemoglobin concentrations is inaccurate in fetofetal transfusion syndrome in utero, the diagnosis of which may necessitate detection of a shared circulation using a marker such as adult red cells.


Metastases involving spinal cord, roots, and plexus.
Neurogenic pain is common in patients with widespread metastatic cancer. Pain of this type is often severe and typically results from neoplastic invasion of the peripheral nerves, spinal roots, or spinal cord. Tumors may invade the cervical, brachial, or lumbosacral plexuses either by direct extension from contiguous structures or in association with metastases to regional soft tissues and lymph nodes. Most of these patients experience progressive pain, motor loss, and sensory dysfunction. Metastases directly to the peripheral nerves are rare in patients with solid tumors but are more frequently encountered in patients with hematologic malignancies. Metastases to the spinal roots and the spinal cord usually occur in patients who also have demonstrable evidence of leptomeningeal or intraparenchymal brain metastases. These conditions may overlap and must be distinguished from other causes of plexus, nerve, or spinal cord disorders in the patient with cancer. Early identification and appropriate treatment allow these patients to remain functional and interactive with family and friends.


Development of a synthetic medium for continuous anaerobic growth and ethanol production with a lactate dehydrogenase mutant of Bacillus stearothermophilus.
A synthetic medium was developed by the pulse and medium-shift technique for the continuous cultivation of Bacillus stearothermophilus strain LLD-15 (NCIMB 12428) under anaerobic conditions. This mutant strain lacks L-lactate dehydrogenase activity, and is a promising candidate for the production of ethanol from pentoses and hexoses, using a high-temperature two-stage process. The final medium contained four amino acids and five vitamins, and growth characteristics in this medium compared well with those in complex medium containing yeast extract and tryptone. At 70 degrees C, the medium was capable of supporting good anaerobic and aerobic growth at 10 g input sucrose l-1. High ethanol production indicated that pyruvate metabolism probably occurred via the combined activity of the pyruvate-formate-lyase pathway and pyruvate dehydrogenase.


Bacterial associations reveal spatial population dynamics in Anopheles gambiae mosquitoes.
The intolerable burden of malaria has for too long plagued humanity and the prospect of eradicating malaria is an optimistic, but reachable, target in the 21(st) century. However, extensive knowledge is needed about the spatial structure of mosquito populations in order to develop effective interventions against malaria transmission. We hypothesized that the microbiota associated with a mosquito reflects acquisition of bacteria in different environments. By analyzing the whole-body bacterial flora of An. gambiae mosquitoes from Burkina Faso by 16 S amplicon sequencing, we found that the different environments gave each mosquito a specific bacterial profile. In addition, the bacterial profiles provided precise and predicting information on the spatial dynamics of the mosquito population as a whole and showed that the mosquitoes formed clear local populations within a meta-population network. We believe that using microbiotas as proxies for population structures will greatly aid improving the performance of vector interventions around the world.


Relationship between duration of diagnosis and neuromusculoskeletal complications of middle-aged type 2 diabetes patients.
Patients with Type 2 Diabetes (T2D) often present with complications involving the neuromusculoskeletal system which creep in as the condition advances in years. Hence there is a need to further understand how the duration of diagnosis of diabetes (DD) relates to the neuromusculoskeletal complications in order to design timely preventive programmes. To investigate the relationship between the duration of diabetes and neuromusculoskeletal complications in type 2 diabetes. This was a cross-sectional survey involving 139 consenting T2D patients and 139 age and sex-matched nondiabetic individuals. The participants were assessed for the DD and selected neuromusculoskeletal complications including muscle weakness, ranges of motion (ROM), pain and foot ulceration. The mean DD was 7.82 ± 2.41 years. There were significant differences (p < 0.01) between the clinical variables of both groups. In the diabetic participants, significant inverse relationships (P<0.05) were obtained between the DDD and each of muscle strength {{lbow flexors (r =-0.57), knee extensors (r=-0.63), handgrip (r=-0.82)}; ROM {wrist extension (r=-0.64) and ankle planterflexion (r=-0.63)}. Significant and direct relationships were obtained between the DDD and each of pain (r=0.62) and ulcerative grading (r= 0.81). Type 2 Diabetes patients have poorer neuromusculoskeletal variables and longer duration of diabetes is associated with reduced muscle strength, diminished ROM, gradual ulceration of skin of the feet and higher level of foot pain. Immediate therapeutic exercises against these complications soon after diagnosis of diabetes may help to decelerate their progression.


Benign adrenal cyst presenting in a pregnant patient.
Cystic lesions of the adrenal gland are uncommon, most often diagnosed incidentally during diagnostic imaging or autopsy. An adrenal cyst presenting as a pelvic mass in pregnancy offers the clinician a diagnostic and therapeutic dilemma. A 28-year-old black female presented for routine obstetric care at 26 weeks' gestation and was found on examination to have a 40-cm pelvic-abdominal mass. Ultrasound confirmation revealed the mass to be cystic and arising from the right pelvis. Laboratory tests including hematocrit, white blood cell count, electrolytes, rapid plasma reagin (RPR), and CA-125 were within normal limits. The patient underwent exploratory laparotomy and a 40 x 20 cm right adrenal cyst was identified and resected. Postoperatively, the patient developed preterm labor and delivered a 955-g infant; the infant was discharged home 3 months later with bronchopulmonary dysplasia and delayed developmental milestones. The woman was discharged home without complication on postoperative Day 8. Accurate preoperative determination of the origin of a pelvic mass occurring in pregnancy is helpful in timing therapeutic intervention. Use of ultrasound and magnetic resonance imaging (MRI) modalities can provide detailed anatomical information without risk to mother or fetus. Conservative management of adrenal cyst in pregnancy may lower the morbidity and mortality of the mother and fetus.


CircFAT1 Promotes the Proliferation and Invasion of Malignant Melanoma through miR375-SLC7A11 Signal Axis.
Circular RNA, as a member of noncoding RNA, plays an important role in the occurrence, development and metastasis of tumor cells. So far, the correlation between circular RNA and malignant melanoma remains obscure. RNA expression of circFAT1 and miR-375 in malignant melanoma (MM) tissues and cell lines was detected by RT-PCR. The proliferation, cloning, migration and invasion of SK-Mel-28 and A375 cells were assessed using CCK-8 test, clone formation and Transwell assay, respectively. CircRNA immunoprecipitation was used to validate the relationship between circFAT1 and miR-375. The binding between circFAT1 and miR-375, as well as SLC7A11 and miR-375 were verified by luciferase assay. In our study,the circFAT1 was significantly overexpressed in the MM tissue than melanocytic nevi. Conversely, the expression of miR-375 in MM tissue was lower than in melanocytic nevi tissue. The underexpression of circFAT1 with siRNA plasmids significantly suppressed the proliferation, invasion and clone formation of MM cell line. Mechanistically, circFAT1 positively regulates the expression level of SLC7A11 by sponging miR-375. The promotive effects of circFAT1 on the proliferation and invasion ability of MM cells were reversed by the upregulation of miR-375. circFAT1 promotes the proliferation, invasion and clone formation of malignant melanoma cells by improving the expression level of SLC7A11 via sponging miR-375.


Evaluation of the Voluntary Johne's Disease Herd Status Program as a source of replacement cattle.
The objectives of this study were to evaluate the perceived value that enrolled producers gained from participation in the Voluntary Johne's Disease Herd Status Program (VJDHSP), and to evaluate the risk of infection with Mycobacterium avium ssp. paratuberculosis (MAP) of cattle reared in a presumed Johne's free environment vs. cattle raised in an environment of unknown Johne's status. Producers enrolled in level 3 or 4 of the VJDHSP (98 and 99% probability, respectively, of being free from MAP infection) were interviewed via telephone. Producers were asked questions pertaining to their participation in the VJDHSP, and asked to identify herds to which they had sold replacement heifers. These cattle were presumed to be uninfected before sale. Fifty-nine cattle (identified as having been purchased into infected herds as heifers) were identified as having been raised in uninfected herds and sold to producers with herds of unknown Johne's disease status. On the purchasing farm, fecal and blood samples were collected from each cow of VJDHSP origin and 3 randomly selected home-reared cows per VJDHSP cow matched by lactation as controls. Samples were tested using commercial ELISA (serum) and bacterial culture (feces). Results indicated that enrolled producers saw value in VJDHSP participation, and that cattle reared in VJDHSP herds were less likely to be infected with MAP than herdmates as measured by serum ELISA MAP antibody and by fecal culture. This study provides evidence of the value of the VJDHSP in providing economic value to participants and supports the promotion of VJDHSP herds as a source of replacement cattle of low infection risk for MAP.


Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans.
It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.


Pyrazolone derivatives: synthesis, anti-inflammatory, analgesic, quantitative structure-activity relationship and in vitro studies.
Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3- and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.


Acquisition of Early Developmental Milestones and Need for Special Education Services in Pediatric Multiple Sclerosis.
Children with pediatric-onset multiple sclerosis and pediatric controls were enrolled across 16 pediatric multiple sclerosis centers in the United States and completed questionnaires that addressed time of first unaided walking and acquisition of 2-word phrases. A total of 467 (308 female) cases and 428 (209 female) controls were enrolled. Pediatric multiple sclerosis (n = 467) were not delayed in walking or using 2-word phrases compared to healthy controls (n = 428) (2.2% vs 5.7%, respectively). Children with disease onset before age 11 versus onset at 11 years or after were more likely to need an individualized education plan (P = .002), reading assistance (P = .0003), and math assistance (P = .001). Children with multiple sclerosis onset prior to age 18 are not delayed in meeting the 2 major early developmental milestones but do have a significantly increased use of special services or learning assistance at school. Further research will need to address whether other measures of development (eg, rate of language acquisition or fine motor skills) differ between pediatric multiple sclerosis and controls.


Disruption of ER-mitochondria tethering and signalling in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia.
Hexanucleotide repeat expansions in C9orf72 are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mechanisms by which the expansions cause disease are not properly understood but a favoured route involves its translation into dipeptide repeat (DPR) polypeptides, some of which are neurotoxic. However, the precise targets for mutant C9orf72 and DPR toxicity are not fully clear, and damage to several neuronal functions has been described. Many of these functions are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. ER-mitochondria signalling requires close physical contacts between the two organelles that are mediated by the VAPB-PTPIP51 'tethering' proteins. Here, we show that ER-mitochondria signalling and the VAPB-PTPIP51 tethers are disrupted in neurons derived from induced pluripotent stem (iPS) cells from patients carrying ALS/FTD pathogenic C9orf72 expansions and in affected neurons in mutant C9orf72 transgenic mice. In these mice, disruption of the VAPB-PTPIP51 tethers occurs prior to disease onset suggesting that it contributes to the pathogenic process. We also show that neurotoxic DPRs disrupt the VAPB-PTPIP51 interaction and ER-mitochondria contacts and that this may involve activation of glycogen synthase kinases-3β (GSK3β), a known negative regulator of VAPB-PTPIP51 binding. Finally, we show that these DPRs disrupt delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB-PTPIP51 tethers. This delivery regulates a number of key neuronal functions that are damaged in ALS/FTD including bioenergetics, autophagy and synaptic function. Our findings reveal a new molecular target for mutant C9orf72-mediated toxicity.


'Near-miss' for sudden infant death syndrome infants: a clinical problem.
Three hundred six infants were referred for evaluation of "near-miss" sudden infant death syndrome (SIDS) from 1973 to 1980. Following the hospitalization and medical evaluation, there were 156 infants (115 term and 41 preterm) for whom there was no explanation for the presenting event and who were considered near-miss infants; 88% of these infants were seen during the first 3 months of life. A repeat near-miss event was reported in 63% (term) and 83% (preterm) infants. Twelve percent of term infants and 17% of the preterm infants had ten or more repeat events. A home apnea/cardiac monitor was prescribed for 88% of the infants for an average duration of 5.6 months in term infants and 3.5 months in preterm infants. Monitoring had been discontinued in 69% of the infants by 7 months of age. One full-term infant was later a SIDS victim. The risk of a repeat near-miss event is concluded to be sufficiently great to demand immediate hospitalization, medical evaluation, home monitoring when there is no specific treatment, and close clinical follow-up. Follow-up studies are needed to determine whether there is any long-term morbidity for infants who have had near miss events.


Determination of the Isotopic Enrichment of 13C- and 2H-Labeled Tracers of Glucose Using High-Resolution Mass Spectrometry: Application to Dual- and Triple-Tracer Studies.
Multiple-tracer approaches for investigating glucose metabolism in humans usually involve the administration of stable and radioactive glucose tracers and the subsequent determination of tracer enrichments in sampled blood. When using conventional, low-resolution mass spectrometry (LRMS), the number of spectral interferences rises rapidly with the number of stable tracers employed. Thus, in LRMS, both computational effort and statistical uncertainties associated with the correction for spectral interferences limit the number of stable tracers that can be simultaneously employed (usually two). Here we show that these limitations can be overcome by applying high-resolution mass spectrometry (HRMS). The HRMS method presented is based on the use of an Orbitrap mass spectrometer operated at a mass resolution of 100 000 to allow electrospray-generated ions of the deprotonated glucose molecules to be monitored at their exact masses. The tracer enrichment determination in blood plasma is demonstrated for several triple combinations of 13C- and 2H-labeled glucose tracers (e.g., [1-2H1]-, [6,6-2H2]-, [1,6-13C2]glucose). For each combination it is shown that ions arising from 2H-labeled tracers are completely differentiated from those arising from 13C-labeled tracers, thereby allowing the enrichment of a tracer to be simply calculated from the observed ion intensities using a standard curve with curve parameters unaffected by the presence of other tracers. For each tracer, the HRMS method exhibits low limits of detection and good repeatability in the tested 0.1-15.0% enrichment range. Additionally, due to short sample preparation and analysis times, the method is well-suited for high-throughput determination of multiple glucose tracer enrichments in plasma samples.


Transcriptional corepressors in cancer: emerging targets for therapeutic intervention.
The normal cell transcriptional process entails a high degree of combinatorial effects and time-dependent "flexibility" to translate cellular signaling into differential gene expression levels. Transcriptional corepressors can function as histone-modifying enzymes to regulate epigenetic events, modulate chromatin structure, and hence control transcriptional activity. Various corepressor complexes have been described; qualitative and quantitative alterations of corepressors can crucially influence the transcriptional output of both normal and malignant cells. Because these molecules can exert epigenetic control of tumorigenic signaling pathways, they can be considered potential regulators of cancer cell-related phenomena. Alterations of the expression level and/or function of transcriptional corepressors have been reported in a wide range of human cancers; thus, corepressors may present rational therapeutic targets as well as potential biomarkers of response to selective therapeutic interventions. Deeper insights into the context-specific and time-specific physical connections among transcription factors, coregulators, and gene regulatory elements, as well as epigenetic modifications, and their interactions, can enhance the capacity to interfere with small molecules that may restore the normal transcriptome/interactome in a cancer cell. There are several conceivable mechanisms of corepressor targeting in cancer that create enthusiasm. However, design, discovery, and testing of such innovative treatment approaches require extensive elaboration before they can achieve practical implementation in the clinic.


Telomerase reverse transcriptase promoter regulation during myogenic differentiation of human RD rhabdomyosarcoma cells.
During terminal differentiation of human and murine cells, telomerase activity and parallel transcription of telomerase reverse transcriptase (hTERT) are inhibited. In this study, we used in vitro and in vivo analyses to determine the role of hTERT promoter elements and associated factors during differentiation-induced inhibition of telomerase expression in RD, a human rhabdomyosarcoma cell line. Assay of telomerase enzyme activity, hTERT mRNA, and reporter gene assays confirmed that the hTERT promoter was silenced during 12-O-tetradecanoylphorbol-13-acetate-induced myogenic differentiation of telomerase-positive RD cells. Promoter deletion and mutation analyses revealed that two E-boxes and an AP-2 site present in a 320-bp region of the promoter were essential for the transcriptional activity of the hTERT gene. Electrophoretic mobility shift assays identified several factors that interact with this region of DNA, including the muscle-specific transcription factors Myf5, Myf6, and myogenin and the ubiquitously expressed factors Sp1 and AP-2. Ectopic expression of the E-box binding factors c-Myc and Mad did influence promoter activity in these cells; indeed, the presence of endogenous c-Myc protein was altered after differentiation. Our findings suggest that the acute regulation of hTERT transcription is primarily controlled by E-box elements, which bind a series of factors during the phased phenotypic changes occurring during the differentiation of RD human muscle cells.


Influence of single-fraction Gamma-Knife radiosurgery on ocular surface and tear function in choroidal melanoma patients.
To evaluate ocular surface and tear function in patients with choroidal melanoma treated with single-fraction radiosurgery. 36 patients (median age 62 years; range 26-84 years) were enrolled between 2001 and 2006 at a single institution. They were treated with the Leksell Gamma Knife in one fraction with a median dose of 30 Gy (range 25-35 Gy). In both eyes of all patients treated subjective symptom score (visual analogue scale) was evaluated, central corneal sensitivity testing, Schirmer test without local anaesthesia, and corneal and conjunctival staining were performed before therapy and 3, 6, 12, 24 and 36 months thereafter. The respective untreated fellow eye served as control. Three months after radiosurgery, the subjective dry eye symptom score and lissamine green staining score of the ocular surface were significantly higher in the treated eyes compared with the fellow eyes (p<0.001, p=0.028, respectively). After 12 months, a significant difference between the treated and the fellow eyes in corneal sensitivity (p=0.041) and corneal fluorescein staining (p=0.002) was found when compared with pretreatment values. After 24 months Schirmer test values without local anaesthesia were significantly reduced in the treated eyes vis-à-vis untreated fellow eyes and pretreatment values (p=0.004). The dose applied to the lacrimal gland was significantly correlated to ocular surface staining scores (p=0.001) and Schirmer test values (p=0.026) at 24 months after irradiation. Stereotactic single-fraction Gamma-Knife radiotherapy of choroidal melanoma with a median dose of 30 Gy significantly affected ocular surface and tear function and increased dry eye symptoms and signs.


Developing research capacity in health librarians: a review of the evidence.
This critical review considers current issues of research capacity development in UK health care and the role of health librarianship in this context, placing particular focus on the use of research networks. There is a growing literature base recognising the need for librarians to engage more with research. The concepts of evidence-based health librarianship and clinical librarianship are discussed in the context of research and examples of existing good practice are reviewed. It is suggested that librarians should build on this through better consideration of evidence based methodologies, hierarchies of evidence, improvement of research skills, and a collective endeavour to identify research priorities. The importance research capacity is being given in the Department of Health R&D strategy and the use of networks in achieving this is discussed, and it is suggested that the utilisation of networks and collaboration should be undertaken and explored in more depth in developing research capacity in health librarianship. Areas where librarians currently engage with research and use networks and collaborative practices to contribute to the research base are reviewed. A co-ordinated approach to developing research capacity is called for and it is argued that the use of networks would be beneficial in assisting the process.


Foams stabilized with solid particles carrying stimuli-responsive polymer hairs.
Submicrometer-sized polystyrene (PS) particles carrying stimuli-responsive poly[2-(diethylamino)ethyl methacrylate] (PDEA) hairs with degrees of polymerization of 30, 60 and 90 were synthesized by dispersion polymerization and used as a particulate foam stabilizer. The effects of the composition of these PDEA-PS particles and foam formation conditions on foamability, foam stability and foam microstructures were extensively investigated. The hairy particles were found to work as an effective stabilizer of aqueous foams in basic media, in which the PDEA hairs are not protonated and thus the particle surfaces exhibit suitable wettability at the air-water interface. In contrast, little to no foam or unstable foams were formed in acidic aqueous media, in which the hairs are protonated and are therefore water soluble. Particles carrying longer hairs resulted in greater foamability and more highly stabilized foams that were capable of persisting for more than one month. Foams were found to form in a narrower pH range when using PS particles with longer hairs, due to both entropic and image charge effects. Data obtained from the touch mixer mixing method showed that both foamability and foam stability increased with increases in the concentration of polymer particles up to 10 wt%, because higher concentrations allowed greater air-water interfacial areas to be stabilized. Conversely, only minimal foam was obtained at and above 15 wt% because of the high viscosity of the resulting aqueous particle dispersion. Trials using the homogenizer mixing method showed that foam with a cream-like texture could be formed even at 40 wt% particle concentration as a result of the improved mixing efficiency. Defoamation could be induced by exposing the foams to HCl vapor. Exposure to acidic vapor led to in situ protonation of the 2-(diethylamino)ethyl methacrylate residues, rendering the PDEA hairs hydrophilic and water soluble, and desorption of the PDEA-PS particles from the air-water interface.


NAS and APS Meetings: Changes in Moods and in Modes.
The National Academy of Sciences (NAS) and the American Physical Society (APS) both met in Washington in the week after Easter. Beyond the coincidence of time and place it is fair to say that the meetings shared a common mood. The truce in Vietnam is generally regarded as the principal cause of a muting of the voices of protest that have been heard at so many scientific meetings in recent years and finally had disturbed the even tenor of the academy's ways. Particularly at APS there seems to be new interest and energy directed to exploring ways to work within the system.


Incidence and Types of Pediatric Nystagmus.
To report the incidence, prevalent subtypes, and clinical characteristics of pediatric nystagmus diagnosed over a 30-year period. Retrospective, population-based study. Using the Rochester Epidemiology Project, we reviewed the medical records of all children (<19 years) diagnosed as residents in Olmsted County, Minnesota, with any form of nystagmus from January 1, 1976, through December 31, 2005. Seventy-one children were diagnosed during the 30-year period, yielding an annual incidence of 6.72 per 100,000 younger than 19 years (95% confidence interval [CI], 5.15-8.28) Infantile nystagmus, onset by 6 months, comprised 62 (87.3%) of the study patients, corresponding to a birth prevalence of 1 in 821. The median age at diagnosis for the cohort was 12.7 months (range, 0 days to 18.6 years) and 42 subjects (59.2%) were male. The main types of nystagmus, in declining order, were nystagmus associated with retinal/optic nerve disease in 23 (32.4%), idiopathic or congenital motor nystagmus in 22 (31.0%), manifest latent nystagmus or latent nystagmus in 17 (24.0%), and 2 (2.8%) each associated with Chiari malformation, medication use, tumor of the central nervous system, and no diagnosis. Developmental delay was diagnosed in 31 (43.6%), strabismus in 25 (35.2%), and amblyopia in 10 (14.1%). Eighty percent had 20/40 (or equivalent) or better vision at presentation in at least 1 eye. This study provides population-based data on incidence and clinical characteristics of childhood nystagmus in North America. Idiopathic and nystagmus associated with retinal/optic nerve disease were the most common presentations, with most patients having good vision. Developmental delay, strabismus, and amblyopia were common in this cohort.


The Impact of Team Knowledge Heterogeneity on Entrepreneurial Opportunity Identification: A Moderated Mediation Model.
Due to the low success rate of entrepreneurship, the correct identification of entrepreneurial opportunities is one of the important concerns in the field of entrepreneurship research. Therefore, this study focuses on the influence mechanism of entrepreneurial opportunity identification, so as to enrich the influence path of entrepreneurial opportunity identification and provide suggestions for improving the success rate of entrepreneurship. After screening and judging the quality of the questionnaires, the valid questionnaires were numbered and matched with 106 team samples. The researchers carried out telephone communication with participants to ask for their attendance, and then took samples on-site at the appointed time and place. The results show that: (1) team knowledge heterogeneity has a significant positive impact on entrepreneurial opportunity identification. (2) Social capital plays a mediating role between team knowledge heterogeneity and entrepreneurial opportunity identification. (3) Promotional regulatory focus, a type of regulation that tends to adopt a radical approach to achieve goals, positively moderates the mediating effect of team knowledge heterogeneity on entrepreneurial opportunity identification through social capital. However, preventive regulatory focus, a type of regulation that tends to adopt a cautious and vigilant way to achieve goals, has no moderating effect. In order to improve the correct identification of entrepreneurial opportunities, it is necessary to establish team with knowledge heterogeneity rationally and excavate different levels of social capital behind heterogeneous members. In addition, it also reveals that team style can retain certain promotive in the process of entrepreneurship, which is conducive to the feasibility and profitability of entrepreneurial opportunity identification.


An overview of inverted colloidal crystal systems for tissue engineering.
Scaffolding is at the heart of tissue engineering but the number of techniques available for turning biomaterials into scaffolds displaying the features required for a tissue engineering application is somewhat limited. Inverted colloidal crystals (ICCs) are inverse replicas of an ordered array of monodisperse colloidal particles, which organize themselves in packed long-range crystals. The literature on ICC systems has grown enormously in the past 20 years, driven by the need to find organized macroporous structures. Although replicating the structure of packed colloidal crystals (CCs) into solid structures has produced a wide range of advanced materials (e.g., photonic crystals, catalysts, and membranes) only in recent years have ICCs been evaluated as devices for medical/pharmaceutical and tissue engineering applications. The geometry, size, pore density, and interconnectivity are features of the scaffold that strongly affect the cell environment with consequences on cell adhesion, proliferation, and differentiation. ICC scaffolds are highly geometrically ordered structures with increased porosity and connectivity, which enhances oxygen and nutrient diffusion, providing optimum cellular development. In comparison to other types of scaffolds, ICCs have three major unique features: the isotropic three-dimensional environment, comprising highly uniform and size-controllable pores, and the presence of windows connecting adjacent pores. Thus far, this is the only technique that guarantees these features with a long-range order, between a few nanometers and thousands of micrometers. In this review, we present the current development status of ICC scaffolds for tissue engineering applications.


Hierarchical object recognition in Pelvic CT Images.
This paper introduces a hierarchical method of recognizing bone tissue from regions extracted from Pelvic CT Images. The method allows distinguishing among segmented objects with similar grey level values, such as bone tissue and regions of active hemorrhage. The method addresses the challenge of correctly segmenting and classifying bone as well as assessing presence of active hemorrhage.


Corrigendum to: Medication-taking behaviour in New South Wales patients with type 2 diabetes: an observational study.
This study aimed to (1) determine adherence to diabetes medication in type 2 diabetes (T2D) patients; (2) describe respondents' attitudes and beliefs about medications, and barriers to adherence; and (3) to model predictors of non-adherence. Data were collected using online and postal surveys. Diabetes patients aged ?18 years who were members of the Australian Diabetes Council were invited to participate. Main outcome measures were adherence to diabetes medication using 8-item Morisky Medication Adherence Score (MMAS-8) and beliefs about medication using the Beliefs about Medicines Questionnaire. A total of 543 T2D patients responded to the survey. The median (interquartile range) MMAS-8 score was 6.8 (5.0-7.0). The prevalence of adherence (MMAS-8 score ?6) was 64.6%. The proportion of respondents who expressed concern about taking medications was 53.6%. Potential predictors of adherence included age (OR, 1.83; 95% CI, 1.19-2.82), concern about medication (OR, 0.91; 95% CI, 0.87-0.96), knowledge of diabetes (OR, 0.85, 95% CI, 0.73-0.99), having difficulty in paying for medication (OR, 0.51; 95% CI ,0.33-0.79), having more than one regular pharmacy (OR, 0.59; 95% CI, 0.36-0.95), and using insulin (OR, 0.49; 95% CI, 0.30-0.81). Adherence to taking diabetes medication in a sample of the Australian T2D patient population was suboptimal. An understanding of medication-taking behaviour will assist health-care professionals to deliver appropriate and effective interventions to enhance adherence and optimise diabetes control in T2D patients.


Prevalence of proximal contact loss between implant-supported fixed prostheses and adjacent natural teeth and its associated factors: a 7-year prospective study.
The aim was to analyze the prevalence rate of proximal contact loss (PCL) between implant-fixed prostheses (IFPs) and adjacent teeth and investigate the associated factors. One hundred fifty participants were recruited for this prospective study from January 2009 to December 2014. Two hundred thirty-four IFPs supported by 384 implants for the posterior region were followed up until June 2016. The contact tightness had been recorded using aluminum strips of different thicknesses with a regular interval after delivery. Proximal contact was considered as lost if the contact tightness was over 50 μm, and statistical analyses were performed to estimate the prevalence rate of PCL and its influential factors. Among the total 299 proximal contacts of 234 IFPs, 179 were observed as a PCL (59.9%). Bone level and root configuration of the adjacent teeth, the proximal contact position and jaw position of the implant prostheses were statistically significant factors, when analyzed by the cumulative PCL rate using the log-rank test of the Kaplan-Meier method (P < 0.05) According to the Cox proportional hazard regression analysis, the proximal contact position, bone level of adjacent teeth and jaw position were revealed to be statistically significant (P < 0.05). PCL should be considered an implant prosthesis complication to which various associated factors could be related. This study revealed that the lower alveolar bone support level of the adjacent teeth, maxillary position of IFPs and mesial site of IFPs were significantly associated with a higher incidence of PCL.


Integration of X-ray microanalysis and morphometry of biological material.
It was investigated how to extract both morphometrical and X-ray elemental information from scanning electron microscopical (SEM) or scanning transmission electron microscopical (STEM)-images and how to integrate these two information streams either on line or off-line after storage. Cytochemical reaction products in cell organelles in ultrathin sections are the biological structures of interest. In such organelles four different situations can be met: morphologically the structures are homomorph or heteromorph; chemically the elements are distributed either homogeneously or heterogeneously. A new program has been proposed and described, which permits determination of both the area and the mean net-intensity value of chemical elements, inhomogeneously distributed over heteromorph organelles. The value of this integration method is demonstrated by three examples of increasing complexity, starting with two elements which are more or less homogeneously distributed over one lysosome, the establishing of a platinum discontinuity in an acidophilic granule and finally the localization of two chemical elements inhomogeneously distributed over a rather heteromorph phagolysosome. In two examples Chelex ion exchange beads, maximally loaded with the element also present in the structure of interest, are co-embedded with the tissue as internal standards. In such cases the absolute elemental concentration in the structures analysed can be established. The presence of such cross-sectioned beads in the ultrathin sections is also used: to demonstrate their function as models to select the proper conditions for the digital-controlled raster analysis of the unknown cell- or tissue structures, to prove the value of this method.


Acute Bromide Intoxication in a Patient with Preserved Renal Function.
BACKGROUND Electrolyte imbalance is frequent in many situations, but severe hyperchloremia is markedly rare in the absence of renal impairment. We report a patient with preserved renal function who exhibited severe hyperchloremia and negative anion gap. CASE REPORT A 70-year-old female with preserved renal function presented with fatigue and impaired consciousness. Venous blood gas analysis was notable for a chloride level of 137 mEq/L and anion gap of -18.2 mEq/L. Careful history taking revealed that she had taken bromide-containing over-the-counter painkillers. Her symptoms and laboratory tests gradually improved after intravenous hydration and painkiller withdrawal. The serum level of bromide ions on admission was later found to be 4-times higher than that considered toxic. CONCLUSIONS It is important to recognize that hyperchloremia with a negative anion gap strongly suggests bromide intoxication, and that bromide intoxication can develop even in patients with preserved renal function. Careful history taking is essential to the diagnosis because some over-the-counter drugs that are widely available and a few prescription drugs contain bromides.


[Treatment of patients with stage III non-small cell lung cancer: concurrent high-dose chemotherapy and radiotherapy].
The treatment of patients with locally advanced non-small cell lung cancer (stage III) has changed significantly in the past few years. Patients with a non-resectable stage IIIA/B tumour are given combined treatment consisting ofchemotherapy and radiotherapy. These can be administered sequentially or concurrently. It has been shown recently that concurrent chemoradiotherapy gives a survival advantage in comparison with sequential chemoradiotherapy. Cisplatin and etoposide are usually the drugs of choice for chemotherapy in patients with stage III cancer. A biologically effective dose of radiotherapy equivalent to 60-66 Gy, over a maximum of 6.5 weeks, should be given. Surgery is possible for a selected group of patients, provided a complete objective mediastinal response has been achieved after chemoradiotherapy and a complete resection appears to be technically feasible. It is recommended to apply this treatment in a research setting. High-dose concurrent chemoradiotherapy is advised as the standard treatment for stage III non-small cell lung cancer in patients in good physical condition.


alpha-Keto amides as precursors to heterocycles--generation and cycloaddition reactions of piperazin-5-one nitrones.
alpha-Keto amides 10a,b, formed from reaction of pyruvic or benzoylformic acid with allyl amine are found to present as single rotameric forms whilst their tertiary amido analogues 10c, d present as two rotamers in solution at rt. The hydroxyimino derivatives 8 share the conformational characteristics of their parents. The geometrical make-up of the new alpha-amidooximes is seen to depend on the structure of the starting acid and on the degree of substitution of the amido group. The oxime 8a derived from pyruvic acid and allyl amine is formed solely as the (E)-isomer whilst its tertiary amido analogue 8c is formed as both (E)- and (Z)-isomers. Oximes derived from benzoylformic acid have the opposite selectivity with both geometrical isomers forming from the secondary amide 8b and only the (Z)-isomer from the tertiary amide 8d. With the exception of 8b all oximes were configurationally stable with (Z)-isomers reacting to form isoxazolopyrrolidinones 11--compounds with a relatively rare bicyclic nucleus and (E)-isomers cyclising to piperazin-5-one nitrones 1--ketopiperazine N-oxides have to date only appeared once in the literature. New nitrones were trapped with phenyl vinyl sulfone, dimethyl acetylenedicarboxylate and methyl propiolate yielding isoxazolidine and isoxazoline fused piperazinones 13, 15, 21 and 22. Cycloadducts from dimethyl acetylenedicarboxylate and 8a, b are thermally labile and their rearrangement provides a novel route to pyrrolopiperazinones 16. The structure of a representative isoxazolopyrrolidinone, 11c, and a 2,3-dihydroisoxazoline fused piperazinone, 21b, are unambiguously solved following x-ray structural analysis.


Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma.
The aim of the present study was to investigate the prevalence of c-FLIP [cellular FLICE-inhibitory protein, where FLICE is Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme] expression in gastric adenocarcinoma and its possible implications for the progression of the cancer. Expression of c-FLIP in 48 gastric adenocarcinomas and their normal counterparts was analysed by reverse transcriptase PCR, Western blotting and immunohistochemistry. In situ cell apoptosis was detected by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. As a result, c-FLIP transcripts were constitutively expressed in gastric adenocarcinomas and their levels were significantly higher than those in matched normal tissues ( P < 0.01). Immunohistochemically, the c-FLIP protein was also found to be expressed in all gastric adenocarcinomas (48/48), and 68.8% (33/48) showed an intense immunostaining; in contrast, only 75% (36/48) of normal gastric mucosa showed positive staining and none of them immunostained intensely. The abundance of c-FLIP protein was significantly higher in carcinoma than in normal gastric mucosa (6.93 +/- 0.58 versus 3.19 +/- 0.26, P < 0.01) and showed a reverse correlation with apoptotic index in adenocarcinoma, but not in normal mucosa. In addition, abundance of c-FLIP was significantly associated with lymph node metastasis at both mRNA level ( P < 0.05) and protein level ( P < 0.01). Western-blot analysis showed that the expression levels of the long form of c-FLIP and the short form of c-FLIP in adenocarcinomas were 2.6-fold and 2.8-fold ( P < 0.01) higher than those in normal tissues respectively. However, no significant difference was found between the expression levels of the two isoforms in both adenocarcinomas or normal tissues. In conclusion, overexpression of c-FLIP is tumour specific, which may be one of the in vivo mechanisms by which tumour cells escape from apoptotic death during the malignant transformation, and plays an important role in lymph node metastasis of gastric adenocarcinoma, which ultimately contributes to the tumour progression.


Obtaining spatial information from an extremely unresolved source.
A means to extract spatial information from an extremely unresolved source of light using a single element detector is demonstrated by use of an optical vortex coronagraph. Applications may range from astronomy to microscopy. For example, the centroid and angular extent of an unresolved collection of incoherent point sources is revealed.


Two potential biomarkers identified in mesenchymal stem cells and leukocytes of patients with sporadic amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder caused by degeneration of motor neurons. The cause for most cases of ALS is multi-factorial,this enhances the need to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derived from the bone marrow of six ALS patients (ALS hMSC) and identified two genes, Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and Retinoblastoma (Rb) Binding Protein 9 (RbBP9) with a significant decrease in post transcriptional A to I RNA editing compared to hMSC of healthy individuals. At the transcriptional level we show abnormal expression of these two genes in ALS hMSC by quantitative real time-PCR (qRT-PCR) and Western blot suggesting a problem in the regulation of these genes in ALS. To strengthen this view we tested by qRT-PCR the expression of these genes in peripheral blood leukocytes (PBL) isolated from blood samples of 17 ALS patients and found that CyFIP2 and RbBP9 levels of expression were significantly different compared to the levels of expression of these two genes in 19 normal PBL samples. Altogether we found two novel ALS potential biomarkers in non-neural tissues from ALS patients that may have direct diagnostic and therapeutic implications to the disease.


Effect of residency duty-hour limits: views of key clinical faculty.
To determine the effect of duty-hour limitations, it is important to consider the views of faculty who have the most contact with residents. We conducted a national survey of key clinical faculty (KCF) at 39 internal medicine residency programs affiliated with US medical schools selected by random sample stratified by federal research funding and program size to elicit their views on the effect of duty-hour limitations on residents' patient care, education, professionalism, and well-being and on faculty workload and satisfaction. Of 154 KCF surveyed, 111 (72%) responded. The KCF reported worsening in residents' continuity of care (87%) and the physician-patient relationship (75%). Faculty believed that residents' education (66%) and professionalism, including accountability to patients (73%) and ability to place patient needs above self-interests (57%), worsened, yet 50% thought residents' well-being improved. The KCF reported spending more time providing inpatient services (47%). Faculty noted decreased satisfaction with teaching (56%), ability to develop relationships with residents (40%), and overall career satisfaction (31%). In multivariate analysis, KCF with 5 years of teaching experience or more were more likely to perceive a negative effect of duty hours on residents' education (odds ratio, 2.84; 95% confidence interval, 1.15-7.00). Key clinical faculty believe that duty-hour limitations have adversely affected important aspects of residents' patient care, education, and professionalism, as well as faculty workload and satisfaction. Residency programs should continue to look for ways to optimize experiences for residents and faculty within the confines of the duty-hour requirements.


The linker region between the helicase and primase domains of the bacteriophage T7 gene 4 protein is critical for hexamer formation.
The gene 4 protein of bacteriophage T7, a functional hexamer, comprises DNA helicase and primase activities. Both activities depend on the unidirectional movement of the protein along single-stranded DNA in a reaction coupled to the hydrolysis of dTTP. We have characterized dTTPase activity and hexamer formation for the full-length gene 4 protein (gp4) as well as for three carboxyl-terminal fragments starting at residues 219 (gp4-C219), 241 (gp4-C241), and 272 (gp4-C272). The region between residues 242 and 271, residing between the primase and helicase domains, is critical for oligomerization of the gene 4 protein. A functional TPase active site is dependent on oligomerization. During native gel electrophoresis, gp4, gp4-C219, and gp4-C241 migrate as oligomers, whereas gp4-C272 is monomeric. The steady-state k(cat) for dTTPase activity of gp4-C272 increases sharply with protein concentration, indicating that it forms oligomers only at high concentrations. gp4-C219 and gp4-C241 both form a stable complex with gp4, whereas gp4-C272 interacts only weakly with gp4. Measurements of surface plasmon resonance indicate that a monomer of T7 DNA polymerase binds to a dimer of gp4, gp4-C219, or gp4-C241 but to a monomer of gp4-C272. Like the homologous RecA and F(1)-ATPase proteins, the oligomerization domain of the gene 4 protein is adjacent to the amino terminus of the NTP-binding domain.


Effect of heterologous antibody on human platelets.
The effect of heterologous anti-human platelet antibody on human platelet function was examined in the presence and absence of whole plasma as an in vitro model for antibody-induced immune damage to cells. Heterologous IgG anti-human platelet antibody mediated platelet aggregation and released serotonin from both platelets in plasma and from platelets isolated by gel filtration and increased the availability of platelet acid phosphatase in a dose-response fashion. Anti-platelet antibody failed to release beta-glucuronidase (lysosomal enzyme marker) or cause lactic dehydrogenase loss (cytolysis). The effect of the antiplatelet antibody on platelets proceeded in the absence of complement. The active molecule in the anti-platelet antiserum was isolated in the IgG fraction and all three indicators of platelet injury were mediated by purified monomeric IgG. Thrombin was not required for the antibody-mediated effects, as three thrombin inhibitors failed to block the reaction. EDTA was an effective inhibitor, suggesting a cation requirement; however, as little as 38 muM calcium was sufficient for effective platelet aggregation and release. The inability of acetylsalicylic acid to inhibit the effect of the antiplatelet antibody suggests that heterologous antibody (IgG) induced platelet alteration proceeds by a different mechanism than that mediated by ADP and epinephrine and does not involve endogenous platelet prostaglandin synthesis.


Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.
LFA-1 (alpha(L)beta(2)) mediates cell-cell and cell-extracellular matrix adhesions essential for immune and inflammatory responses. One critical mechanism regulating LFA-1 activity is the conformational change of the ligand-binding alpha(L) I domain from low-affinity (LA), closed form, to the high-affinity (HA), open form. Most known integrin antagonists bind both forms. Antagonists specific for the HA alpha(L) I domain have not been described. Here, we report the identification and characterization of a human antibody AL-57, which binds to the alpha(L) I domain in a HA but not LA conformation. AL-57 was discovered by selection from a human Fab-displaying library using a locked-open HA I domain as target. AL-57 Fab-phage bound HA I domain-expressing K562 cells (HA cells) in a Mg(2+)-dependent manner. AL-57 IgG also bound HA cells and PBMCs, activated by Mg(2+)/EGTA, PMA, or DTT. The binding profile of AL-57 IgG on PBMCs was the same as that of ICAM-1, the main ligand of LFA-1. In contrast, an anti-alpha(L) murine mAb MHM24 did not distinguish between the HA and LA forms. Moreover, AL-57 IgG blocked ICAM-1 binding to HA cells with a potency greater than MHM24. It also inhibited ICAM-1 binding to PBMCs, blocked adhesion of HA cells to keratinocytes, and inhibited PHA-induced lymphocyte proliferation with potencies comparable with MHM24. These results indicate that specifically targeting the HA I domain is sufficient to inhibit LFA-1-mediated, adhesive functions. AL-57 represents a therapeutic candidate for treatment of inflammatory and autoimmune diseases.


Pulsed electromagnetic fields alleviate streptozotocin‑induced diabetic muscle atrophy.
Diabetic muscle atrophy causes a reduction of skeletal muscle size and strength, which affects normal daily activities. However, pulsed electromagnetic fields (PEMFs) can retard the atrophy of type II fibers (ActRIIB) in denervated muscles. Therefore, the purpose of the present study was to determine whether PEMFs can alleviate streptozotocin (STZ)‑induced diabetic muscle atrophy. To do this, 40 Sprague‑Dawley (SD) rats were randomly divided into four groups (n=10 per group): The normal control group (NC; nondiabetic rats without treatment); the diabetic mellitus group (DM; STZ‑induced rats without treatment); the diabetic insulin‑treated group (DT; diabetic rats on insulin treatment, 6‑8 U/d twice a day for 6 weeks) as a positive control; and the diabetic PEMFs therapy group (DP; diabetic rats with PEMFs exposure treatment, 15 Hz, 1.46 mT, 30 min/day for 6 weeks). Body weight, muscle strength, muscle mass and serum insulin level were significantly increased in the DP group compared with the DM group. PEMFs also decreased the blood glucose level and altered the activity of metabolic enzymes. PEMFs significantly increased the cross‑sectional area of muscle fiber. In addition, PEMFs significantly activated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and inhibited the activity of myostatin (MSTN), ActRIIB and forkhead box protein O1 (FoxO1) compared with the DM group. Thus indicating that the Akt/mTOR and Akt/FoxO1 signaling pathways may be involved in the promotion of STZ‑induced diabetic muscle atrophy by PEMFs. The results of the present study suggested that PEMFs stimulation may alleviate diabetic muscle atrophy in the STZ model, and that this is associated with alterations in multiple signaling pathways in which MSTN may be an integral factor. MSTN‑associated signaling pathways may provide therapeutic targets to attenuate severe diabetic muscle wasting.


Broadband tunable integrated CMOS pulser with 80-ps minimum pulse width for gain-switched semiconductor lasers.
High power pulsed lasers with tunable pulse widths are highly favored in many applications. When combined with power amplification, gain-switched semiconductor lasers driven by broadband tunable electric pulsers can meet such requirements. For this reason, we designed and produced a low-cost integrated CMOS pulse generator with a minimum pulse width of 80 ps and a wide tuning range of up to 270 ns using a 40-nm microelectronic process technique. We used this pulser to drive a 1.3-µm semiconductor laser diode directly, and thereafter investigated the gain-switching properties of the laser system. The optical pulses consist of a spike followed by a steady state region. Tuning the width of the electrical pulse down to approximately 1.5 ns produces optical pulses consisting only of the spike, which has a minimum pulse-width of 100 ps. Moreover, the duration of the steady state can be tuned continuously by tuning the electrical pulse width, with a peak power of approximately 5 mW. The output voltage of the electric pulser has a tuning range of 0.8-1.5 V that can be used to directly drive semiconductor laser diodes with wavelengths in the near-infrared spectrum, which are suitable for power amplification with rare-earth doped fiber amplifiers.


Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells.
Protein kinase CK2, a messenger-independent serine/threonine kinase, has been implicated in cell growth. Androgenic stimulus in rat prostate modulates its association with nuclear matrix (NM) and chromatin. Because the growth of human prostate carcinoma cells is influenced by androgens and/or growth factors, we determined the nature of CK2 signaling in the NM in response to androgen and growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3 cells were cultured in media to regulate their growth in the presence of 5alpha-dihydrotestosterone (5alpha-DHT) or growth factors (epidermal growth factor, keratinocyte growth factor, and transforming growth factor alpha). The activity of CK2 was measured in the cytosolic and NM fractions isolated from these cells after treatment with growth stimuli. The changes in CK2 in various fractions were also confirmed by immunoblotting with a specific antibody. LNCaP cells responded to both 5alpha-DHT and growth factors for growth. The presence of these agents in the culture medium evoked a translocation of CK2 to the NM from the cytosol. The PC-3 cells did not respond to 5alpha-DHT for growth but did respond to growth factors. Under these conditions, there was also a translocation of CK2 to the NM concomitant with a decrease in the cytosolic fraction. These results suggest that CK2 translocation to the NM occurs in response to various growth stimuli in cells in culture. Thus, CK2 is a common downstream signal transducer in response to diverse growth stimuli that may relate to the pathobiology of prostate cancer cells.


Biopsy Needle Advancement during Bone Marrow Aspiration Increases Mesenchymal Stem Cell Concentration.
Point-of-care kits to concentrate bone marrow (BM)-derived mesenchymal stem cells (MSCs) are used clinically in horses. A maximal number of MSCs per milliliter of marrow aspirated might be desired prior to use of a point-of-care system to concentrate MSCs. Our objective was to test a method to increase the number of MSCs per milliliter of marrow collected. We collected two BM aspirates using two different collection techniques from 12 horses. The first collection technique was to aspirate BM from a single site without advancement of the biopsy needle. The second collection technique was to aspirate marrow from multiple sites within the same sternal puncture by advancing the needle 5 mm three times for BM aspiration from four sites. Numbers of MSCs in collected BM were assessed by total nucleated cell count of BM after aspiration, total colony-forming unit-fibroblast (CFU-F) assay, and total MSC number at each culture passage. The BM aspiration technique of four needle advancements during BM aspiration resulted in higher initial nucleated cell counts, more CFU-Fs, and more MSCs at the first passage. There were no differences in the number of MSCs at later passages. Multiple advancements of the BM needle during BM aspiration resulted in increased MSC concentration at the time of BM collection. If a point-of-care kit is used to concentrate MSCs, multiple advancements may result in higher MSC numbers in the BM concentrate after preparation by the point-of-care kit. For culture expanded MSCs beyond the first cell passage, the difference is of questionable clinical relevance.


Aboriginal Wingadhan Birrang (woman's journey) of smoking cessation during pregnancy as they participate in the ICAN QUIT in pregnancy pilot step-wedge trial.
Addressing smoking cessation during pregnancy among Aboriginal women is a national priority under the Closing the Gap campaign. There is a need to measure and report interventions to support Aboriginal women during pregnancy. To quantitatively assess women's smoking experiences over a 12 week ICAN QUIT in Pregnancy program. Aboriginal women and/or women expecting an Aboriginal baby reported their smoking experiences through repeated cross-sectional survey at baseline, four weeks, and 12 weeks. Self-reported nicotine dependence measures (heaviness of smoking index, strength of urges and frequency of urges to smoke), intentions to quit smoking, quit attempts, use of nicotine replacement therapy were gathered as well as a carbon-monoxide measure at each time point. Expectant mothers (n=22) of Aboriginal babies participated from six Aboriginal Community Controlled Health Services between November 2016 and July 2017. At 12 weeks women reported (n=17) low heaviness of smoking index 1.21 with high strength of urges 2.64 and frequency of urges 3.00; 12/13 (92%) reported likely/very likely to quit smoking, made a mean 1.67 number of quit attempts, three women (13.6%) quit smoking (validated); 5/16 (31%) reported using nicotine replacement therapy. Participating women made multiple quit attempts demonstrating motivation to quit smoking. Smoking cessation interventions should be tailored to address high strength and frequency of nicotine dependence despite low consumption. Prolonged smoking cessation support is recommended to address physical, behavioural and psychological aspect of smoking. Cessation support should address previous quitting experiences to assess smoking dependence and tailoring of support. Australian and New Zealand Clinicial Trials Registry (Ref #ACTRN12616001603404).


Performance characterization of a rotary centrifugal left ventricular assist device with magnetic suspension.
The MiTiHeart (MiTiHeart Corporation, Gaithersburg, MD, USA) left ventricular assist device (LVAD), a third-generation blood pump, is being developed for destination therapy for adult heart failure patients of small to medium frame that are not being served by present pulsatile devices. The pump design is based on a novel, patented, hybrid passive/active magnetic bearing system with backup hydrodynamic thrust bearing and exhibits low power loss, low vibration, and low hemolysis. Performance of the titanium alloy prototype was evaluated in a series of in vitro tests with blood analogue to map out the performance envelop of the pump. The LVAD prototype was implanted in a calf animal model, and the in vivo pump performance was evaluated. The animal's native heart imparted a strong pulsatility to the flow rate. These tests confirmed the efficacy of the MiTiHeart LVAD design and confirmed that the pulsatility does not adversely affect the pump performance.


Contemporary drug therapies for multiple myeloma.
Multiple myeloma (MM) is an incurable disease characterized by the proliferation of plasma cells. The survival in MM patients has improved significantly in the past decade due to the introduction of novel agents. In this review, we focus on novel agents used in MM, including immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, marizomib and ixazomib citrate), monoclonal antibodies (elotuzumab, siltuximab, daratumumab and BT-062), and drugs affecting an interaction with the tumor microenvironment (anti-VLA4 monoclonal antibody, chemokine CXCR4 inhibitor AMD-3100 and selectin inhibitor GMI-1070). We discuss their mechanism of action, preclinical and clinical outcome in the treatment of MM. Although the development of novel agents has improved the outcomes of MM treatment, most of the patients will still relapse and become refractory to therapy due to development of drug resistance. A better understanding of the biological mechanisms of MM progression, including cellular and molecular events in the MM cells and in their bone marrow microenvironment, is warranted to provide new therapeutic targets and develop new drugs and therapeutic strategies to treat MM.


Lower limb injuries arising from motorcycle crashes.
Motorcycle accidents are the second most common cause of road traffic accidents in both developing and developed countries. In this study we aim to look at the pattern and characteristics of lower limb injuries arising from motorcycle accidents and evaluate early outcome of treatment. All the patients with lower limb injuries arising from motorcycle accidents who presented in our hospital between 1st October 2006 and 30th September 2007 were reviewed. History was obtained and detailed examination was done after resuscitation to determine the site, nature and the characteristics of injuries. Definitive treatment (conservative or operative) given was based on the pattern and type of injuries. Patients were followed up in the clinic for both clinical and radiological review. Functional outcome assessment was commenced after the onset of weight bearing. The data were recorded on a designated proforma and analyzed using a statistical programme. A total of 429 motorcycle accident victims were seen during this period and lower limb injuries represented the commonest type of injury (238, 55.5%). Male:female ratio was 2.2:1 with a mean age of 43.1years. Fractures were the commonest lower limb injuries (73.4%) and closed fractures were commoner than the open fractures. The commonest anatomical location of fractures in lower limbs was tibial shaft. Joint stiffness was found to be the commonest post treatment complication. Lower limb injuries represent the commonest form of injuries among the motorcycle accident victims. Fractures were the commonest type of injury seen and the most common location was shaft of tibia.


Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases.
Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has no known adverse effects and improves cognitive outcomes in patients with mild Alzheimer's disease. In cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. Recent in vitro studies show that another thiamine thioester, O,S-dibenzoylthiamine (DBT), is even more efficient than BFT, especially with respect to its anti-inflammatory potency, and is effective at lower concentrations. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified open thiazole ring derivatives. The identification of the active neuroprotective metabolites and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental, and psychiatric conditions. The present review aims to summarize existing data on the neuroprotective effects of thiamine thioesters and give a comprehensive account.


C242T polymorphism of NADPH oxidase p22phox and recurrence of cardiovascular events in coronary artery disease.
The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear. The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The p22phox genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and RsaI. digestion. Plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70; P=0.014) remained associated with the T allele. The Kaplan-Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (P<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG. The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.


Mueller matrix polarimetry for improved liver fibrosis diagnosis.
An experimental Mueller matrix polarimeter is used to quantify human liver fibrosis by measuring retardance and depolarization of thin biopsies. The former parameter is sensitive to fibrillar collagen, the latter is specifically sensitive to fibrillar collagen around blood vessels, which is not significant for liver fibrosis diagnosis. By using depolarization like a filter, retardance distribution enables distinguishing between disease stages and limits the high degree of observer discrepancy.


Conversion of Sugar to Fat: Is Hepatic de Novo Lipogenesis Leading to Metabolic Syndrome and Associated Chronic Diseases?
Epidemiologic studies suggest a link between excess sugar consumption and obesity, fatty liver disease, metabolic syndrome, and type 2 diabetes mellitus. One important pathway that may link these metabolic diseases to sugar consumption is hepatic conversion of sugar to fat, a process known as de novo lipogenesis (DNL). Mechanistic studies have shown that diets high in simple sugars increase both DNL and liver fat. Importantly, removal of sugar from diets of children with obesity for only 9 days consistently reduced DNL and liver fat and improved glucose and lipid metabolism. Although the sugar and beverage industries continue to question the scientific evidence linking high-sugar diets to metabolic diseases, major health organizations now make evidence-based recommendations to limit consumption of simple sugars to no more than 5% to 10% of daily intake. Clear recommendation about moderating sugar intake to patients may be an important nonpharmacologic tool to include in clinical practice.


Cannabinoid Signaling Selectively Modulates GABAergic Inhibitory Input to OFF Bipolar Cells in Rat Retina.
In the mammalian retina, cannabinoid type 1 receptors (CB1Rs) are well-positioned to alter inhibitory synaptic function from amacrine cells and, thus, might influence visual signal processing in the inner retina. However, it is not known if CB1R modulates amacrine cells feedback inhibition at retinal bipolar cell (BC) terminals. Using whole-cell voltage-clamp recordings, we examined the pharmacological effect of CB1R activation and inhibition on spontaneous inhibitory postsynaptic currents (sIPSCs) and glutamate-evoked IPSCs (gIPSCs) from identified OFF BCs in light-adapted rat retinal slices. Activation of CB1R with WIN55212-2 selectively increased the frequency of GABAergic, but not glycinergic sIPSC in types 2, 3a, and 3b OFF BCs, and had no effect on inhibitory activity in type 4 OFF BCs. The increase in GABAergic activity was eliminated in axotomized BCs and can be suppressed by blocking CB1R with AM251 or GABAA and GABAρ receptors with SR-95531 and TPMPA, respectively. In all OFF BC types tested, a brief application of glutamate to the outer plexiform layer elicited gIPSCs comprising GABAergic and glycinergic components that were unaffected by CB1R activation. However, blocking CB1R selectively increased GABAergic gIPSCs, supporting a role for endocannabinoid signaling in the regulation of glutamate-evoked GABAergic inhibitory feedback to OFF BCs. CB1R activation shape types 2, 3a, and 3b OFF BC responses by selectively regulate GABAergic feedback inhibition at their axon terminals, thus cannabinoid signaling might play an important role in the fine-tuning of visual signal processing in the mammalian inner retina.


Vertebral artery origin angioplasty and primary stenting: safety and restenosis rates in a prospective series.
To report a single centre ongoing experience of endovascular treatment for atherosclerotic vertebral artery origin stenosis in a series of symptomatic patients, with follow up imaging to determine the incidence of restenosis. 14 patients with vertebral artery origin stenosis on catheter angiography were treated. Angioplasty without stenting was undertaken in the first four patients, all of whom had follow up catheter angiography at one year. Subsequently, patients were treated by primary stenting and followed up with colour Doppler ultrasound examination. The procedure was technically successful in all treated arteries, with no immediate complications. The degree of stenosis was reduced from (mean (SD)) 73 (18)% before treatment to 21 (26)% immediately after treatment in the angioplasty alone group (p = 0.059). In the primary stenting patients, the severity of stenosis was reduced from 82 (8)% to 13 (13)% immediately after treatment (p < 0.001). Restenosis to 70% or greater occurred at one year in all four patients initially treated by angioplasty without stenting. One patient subsequently developed further symptoms and was retreated by stenting. One of the 10 patients treated by primary stenting developed restenosis. None of the remaining patients had further posterior circulation ischaemic symptoms during a mean follow up period of 33.6 months (range 1 to 72 months). Restenosis occurs often after vertebral artery origin balloon angioplasty without stenting but is uncommon after stenting. Primary stenting is therefore recommended to maintain patency at this site, and had a low complication rate in this series.


[A case of spontaneous regression of hepatocellular carcinoma with multiple lung metastases].
Spontaneous regression of hepatocellular carcinoma (HCC) is extremely rare. We report a case of 67-year-old man having HBV-associated HCC with multiple lung metastases which regressed spontaneously. The patient had single liver mass and received surgical resection. The mass was confirmed as HCC histopathologically. Nine years after surgical resection, a 3.3 cm sized recurred HCC was detected on the resection margin in CT scan. Transarterial chemoembolization (TACE) was performed 3 times, and lung metastases developed thereafter. The patient received 2 more sessions of TACE, however, metastatic lung nodules were in progress very rapidly. We decided to stop TACE and followed the patient regularly without any anti-cancer treatment. Nine months after development of lung metastasis, the size and number of metastatic lung nodules decreased and were not detected anymore after 14 months. Serum alpha-fetoprotein levels also decreased to normal range and no viable tumor was noted in the liver. The patient is still alive 12 years after the first diagnosis of HCC and 16 months after lung metastasis developed.