Hyperpolarized (13)C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs.
Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for noninvasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional (13)C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), makes it possible to enhance the spin polarization state of (13)C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here, we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-(13)C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo.


CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.
Obstructive sleep apnea is associated with higher levels of blood pressure (BP), which can lead to increased cardiovascular risk. To compare the association of continuous positive airway pressure (CPAP), mandibular advancement devices (MADs), and inactive control groups (placebo or no treatment) with changes in systolic BP (SBP) and diastolic BP (DBP) in patients with obstructive sleep apnea. The databases of MEDLINE, EMBASE, and the Cochrane Library were searched up to the end of August 2015 and study bibliographies were reviewed. Randomized clinical trials comparing the effect of CPAP or MADs (vs each other or an inactive control) on BP in patients with obstructive sleep apnea were selected by consensus. Of 872 studies initially identified, 51 were selected for analysis. Data were extracted by one reviewer and checked by another reviewer. A network meta-analysis using multivariate random-effects meta-regression was used to estimate pooled differences between each intervention. Meta-regression was used to assess the association between trial characteristics and the reported effects of CPAP vs inactive control. Absolute change in SBP and DBP from baseline to follow-up. Of the 51 studies included in the analysis (4888 patients), 44 compared CPAP with an inactive control, 3 compared MADs with an inactive control, 1 compared CPAP with an MAD, and 3 compared CPAP, MADs, and an inactive control. Compared with an inactive control, CPAP was associated with a reduction in SBP of 2.5 mm Hg (95% CI, 1.5 to 3.5 mm Hg; P < .001) and in DBP of 2.0 mm Hg (95% CI, 1.3 to 2.7 mm Hg; P < .001). A 1-hour-per-night increase in mean CPAP use was associated with an additional reduction in SBP of 1.5 mm Hg (95% CI, 0.8 to 2.3 mm Hg; P < .001) and an additional reduction in DBP of 0.9 mm Hg (95% CI, 0.3 to 1.4 mm Hg; P = .001). Compared with an inactive control, MADs were associated with a reduction in SBP of 2.1 mm Hg (95% CI, 0.8 to 3.4 mm Hg; P = .002) and in DBP of 1.9 mm Hg (95% CI, 0.5 to 3.2 mm Hg; P = .008). There was no significant difference between CPAP and MADs in their association with change in SBP (-0.5 mm Hg [95% CI, -2.0 to 1.0 mm Hg]; P = .55) or in DBP (-0.2 mm Hg [95% CI, -1.6 to 1.3 mm Hg]; P = .82). Among patients with obstructive sleep apnea, both CPAP and MADs were associated with reductions in BP. Network meta-analysis did not identify a statistically significant difference between the BP outcomes associated with these therapies.


Effects of miconazole and dodecylimidazole on sterol biosynthesis in Ustilago maydis.
Miconazole at minimal fungitoxic concentrations inhibits ergosterol biosynthesis in sporidia of Ustilago maydis by interference with sterol C14 demethylation. The action is analogous to that of the fungicides triarimol and fenarimol. The fungicide 1-dodecylimidazole at low concentrations (0.1 to 0.25 mug/ml) inhibits sterol C14 demethylation; however, at higher concentrations (1.0 mug/ml or greater) it also inhibits 2,3-oxidosqualene cyclization and subsequent transmethylation. It is postulated that this diversity of effects of 1-dodecylimidazole results from binding of the inhibitor to sterol carrier protein(s).


Zinc-mediated allylation and alkylation of aminals in the presence of TMSCl and diisopropylamine.
An alkylation of aminals with organozinc reagents derived from allyl bromide, benzyl bromide, alpha-bromoacetate, and alpha-bromonitrile proceeded efficiently in the presence of TMSCl and diisopropylamine. This reaction system was applied to the synthesis of an antispasmodic: butaverine.


Interventions for protecting renal function in the perioperative period.
A number of methods have been used to try to protect kidney function in patients undergoing surgery. These include the administration of dopamine, diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors and hydration fluids. For this review, we selected randomized controlled trials, which employed different methods to protect renal function during the perioperative period. In examining these trials, we looked at outcomes such as renal failure and mortality, as well as changes in the renal function tests, including urine output, creatinine clearance, free water clearance, fractional excretion of sodium and renal plasma flow. We searched the Cochrane Central register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1988 to 2004) and hand searched six journals (British Journal of Anaesthesia; Anesthesia and Analgesia; Anesthesiology; Annals of Surgery; Journal of Thoracic and Cardiovascular Surgery and Journal of Vascular Surgery). We selected all randomized controlled trials in adult population undergoing surgery where a treatment measure was used for the purpose of renal protection in the perioperative period. We selected 37 studies for inclusion in this review. As well as analysis of the data from all the studies, we also performed subgroup analysis for type of interventions, types of surgical procedures and those with pre-existing renal dysfunction. We undertook sensitivity analysis on studies with high methodological quality. The review included data from 37 studies, comprising a total of 1227 patients. Of these, 658 received some form of treatment and 569 acted as controls. The interventions were mostly employing different pharmaceutical agents such as dopamine, diuretics, calcium channel blockers. ACE inhibitors or selected hydration fluids. The results indicated that certain interventions showed some benefits, but all the results suffered from significant heterogeneity. Hence we can draw no conclusions about the effectiveness of these interventions in protecting the kidneys during surgery. There is no reliable evidence from available literature to suggest that interventions during surgery can protect the kidneys from damage. However, there is a need for more studies of high methodological quality. One particular area for further studies may be on patients with pre-existing renal dysfunction undergoing surgery.


Effects of calcium dobesilate on glomerulus TIMP1 and collagen IV of diabetic rats.
To observe the effects of calcium dobesilate on the expression of glomerular tissue inhibitor of metalloproteinase 1 (TIMP1), collagen IV, and ultrastructure of glomerular basement membrane in diabetic rats, rats model of diabetes was established by unilateral nephrectomy and intraperitoneal injection of 1% STZ (55 mg/kg), and rats were administered calcium dobesilate 100 mg/ kg (DD group) or distilled water (DM group) respectively. 12 weeks later, the changes in the renal ultrastructure and creatinine clearance rate (Ccr) were examined in each group. The expression of glomerular TIMP1 and collagen IV were studied by immunohistochemical staining. Our results showed that after 12 weeks, the Ccr in DD group increased and was significantly higher than that in DM group. Electron microscopy showed that thickness of glomerular capillary basement membrane (GBM) in Group DD was less than that of DM group. No hyperplasia of collagen fibers was found, and the distance between the holes of endothelial cells in DD group was not as even as that in the normal group, but more even than that of DM group, and podocyte processes was still in order. Immunohistochemical staining of glomeruli showed that expression of TIMP1 and collagen IV in DD group were significantly less than those of DM group DM. It is concluded that calcium dobesilate can improve diabetic nephropathy by inhibiting the over- accumulation of collagen IV and calcium dobesilate may also contribute to diabetes by inhibiting the expression of TIMP1.


Correlation of electrocardiographic left ventricular hypertrophy criteria with left ventricular mass by echocardiogram in obese hypertensive patients.
Left ventricular hypertrophy (LVH) and obesity are important cardiovascular risk factors. This study evaluates the influence of obesity on the diagnostic performance of the most used electrocardiographic criteria for LVH in hypertensive patients. One thousand two hundred four outpatients from the Hypertensive Unit of the Hospital São Paulo, São Paulo, SP, Brazil, were studied. All underwent 12-lead electrocardiogram and echocardiogram. The most known electrocardiographic criteria for LVH were assessed and compared with the left ventricular mass index obtained by echocardiogram in obese and nonobese groups of hypertensive patients. The population's mean age was 57.4 +/- 4.7 years; 351 were men (29.1%) and 853 women (70.8%). Cornell voltage, Cornell duration, Sokolow-Lyon voltage, Romhilt-Estes criteria, and R wave in aVL 11 mm or higher showed a positive correlation with left ventricular mass index (P < .05). Notwithstanding, there were no changes regarding specificity for obese or nonobese characteristics. However, sensitivity had a statistically significant decrease in obese patients in regard to Sokolow-Lyon voltage and Romhilt-Estes criteria and strain pattern (P < .05). Cornell voltage and Cornell duration criteria, Perugia score, R wave in aVL, and QTc variable had no significant changes in diagnostic sensitivity in the obese patients.


Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds.
Thermal drawing is a versatile rapid prototyping method that can freely form microneedle (MN) structures with ultra-high aspect ratio without relying on any complex and expensive process. However, it is still challenging to repeatedly produce MNs with identical shapes using this thermal drawing due to small fluctuations in processing conditions such as temperatures, drawing speeds, drawing heights, or parallelism in the drawing setup. In addition, thermal drawing is only applicable to thermoplastic materials and most natural biomaterials are incompatible with this method. Thus, we propose use of thermal drawing to fabricate master molds with high aspect ratios and replicate the shape by micromolding. In this work, high A/R MNs with various body profiles were fabricated by thermal drawing and replicated to silk fibroin (SF) MNs multiple times using micromolding. The original MN shape was precisely copied to the SF MNs. Methanol treatment enhanced the mechanical strength of SF MNs up to about 113% more depending on the treatment duration. We also demonstrated that methanol exposure time could effectively control drug release rates from SF MNs.


Stretching with children with cerebral palsy: what do we know and where are we going?
To review research regarding mechanisms of muscle contracture in cerebral palsy (CP) and the effectiveness of stretching, and to discuss current physical therapy stretching practices. Community-based recreation opportunities that encourage flexibility and fitness are explored as alternatives to traditional therapy stretching approaches. Mechanisms of muscle contracture in children with CP are unclear and clinical research evaluating the effects of stretching is inconclusive. Recent shifts in thinking about the management of children with CP suggest an increased emphasis on flexibility, fitness, and participation in activities that are meaningful to children and families. Additional research is needed to explore the structural changes that occur in the shortened muscles of children with CP and the effects of stretching practices used in pediatric physical therapy. Physical therapists can consider innovative alternatives that integrate flexibility and fitness goals with community-based recreation programs.


Antifungal activities of LysM-domain multimers and their fusion chitinases.
PrChiA is an antifungal chitinase obtained from Pteris ryukyuensis, a fern plant. It consists of two N-terminal lysin motif (LysM) domains and a C-terminal catalytic domain of glycoside hydrolase family 18. Previous studies have shown that the deletion of LysM domains or loss of hydrolytic activity causes the loss of the antifungal activity of chitinases. In this study, we produced LysM-domain multimers (LysMn, n = 2-5) and the respective multimer fusion chitinases (LysMn-Cat, n = 1-4), and characterized their enzymatic and antifungal properties. LysMn and LysMn-Cat showed a higher affinity to insoluble chitin than single LysM domain and single catalytic domain alone, respectively. LysMn-Cat hydrolyzed insoluble chitin more efficiently than the catalytic domain alone. Surprisingly, LysMn showed antifungal activity without chitinolytic activity. Further, LysMn-Cat exhibited a stronger antifungal activity than LysMn. Microscopic observation revealed that LysMn attacked only the tips of the fungal hyphae; LysMn-Cat attacked not only the tips, but also the lateral walls around the septa of the fungal hyphae. It is suggested that the LysMn act on the growing point of the hyphal tip through their chitin-binding ability and that the LysMn-Cat act on not only the hyphal tips, but also on the lateral walls through their chitin-hydrolyzing and -binding activities.


The association of glucagon with disease severity and progression in patients with autosomal dominant polycystic kidney disease: an observational cohort study.
Mammalian target of rapamycin (mTOR) inhibitors and ketogenesis have been shown to ameliorate disease progression in experimental autosomal dominant polycystic kidney disease (ADPKD). Glucagon is known to lower mTOR activity and stimulate ketogenesis. We hypothesized that in ADPKD patients, higher endogenous glucagon is associated with less disease severity and progression. Data were analysed from 664 Dutch ADPKD patients participating in the Developing Intervention Strategies to Halt Progression of ADPKD observational cohort, including patients >18 years of age with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and excluding patients with concomitant diseases or medication use that may impact the natural course of ADPKD. The association between glucagon and disease severity and progression was tested using multivariate linear regression and mixed modelling, respectively. The median glucagon concentration was 5.0 pmol/L [interquartile range (IQR) 3.4-7.2) and differed significantly between females and males [4.3 pmol/L (IQR 2.9-6.0) and 6.6 (4.5-9.5), P < 0.001, respectively]. Intrasubject stability of glucagon in 30 patients showed a strong correlation (Pearson's correlation coefficient 0.893; P < 0.001). Moreover, glucagon showed significant associations with known determinants (sex, body mass index and copeptin; all P < 0.01) and known downstream effects (glucose, haemoglobin A1c and cholesterol; all P < 0.05), suggesting that glucagon was measured reliably. Cross-sectionally, glucagon was associated with eGFR and height-adjusted total kidney volume, but in the opposite direction of our hypothesis, and these lost significance after adjustment for confounders. Glucagon was not associated with an annual decline in kidney function or growth in kidney volume. These data do not provide evidence for a role of endogenous glucagon as a protective hormone in ADPKD. Intervention studies are needed to determine the relation between glucagon and ADPKD.


The association of fluoride in drinking water with serum calcium, vitamin D and parathyroid hormone in pregnant women and newborn infants.
Chronic exposure to fluoride in drinking water causes an increase in plasma fluoride levels that is related to a reduction in calcium transport across the renal tubule endoplasmic reticulum and plasma membrane. In the present study, it was hypothesised that varying levels of fluoride present in drinking water are associated with serum levels of calcium and the related hormones vitamin D and parathyroid hormone in pregnant women and newborn infants. This cross-sectional study included two groups based on the fluoride concentration in drinking water. One group was considered low/optimum in which the fluoride concentration in drinking water was <1 ppm, and the other group was considered a high fluoride group with ≥1 ppm fluoride in drinking water. In each group, 90 pregnant women were recruited at the hospital during delivery. The participants were given a questionnaire regarding their medical history, sunshine exposure duration, and supplement use and a food frequency questionnaire (FFQ). Fluoride was measured in drinking water, urine, maternal serum and cord blood. Serum calcium, vitamin D, and parathyroid hormone were measured in a fully automated analyser. In pregnant women, drinking water that contained fluoride was significantly positively correlated with urine and blood serum. Low mean concentrations of vitamin D and deficient (<10 ng/ml) vitamin D were more prevalent among the high fluoride group irrespective of diet, sunshine exposure and supplementation. Serum calcium and parathyroid hormone (PTH) levels were significantly lower in the high fluoride group than in the low/optimum fluoride group in both pregnant mothers' blood and cord blood. Drinking water with high fluoride levels was significantly associated with calcium and the related hormones vitamin D and parathyroid hormone.


How precisely do SPECT images reflect tracer uptake in myocardial infarction? A comparison of thallium-201 and technetium-99m using a myocardial phantom.
We compared the count ratios of 201TI and 99mTc on SPECT images and the true radioactivity in a myocardial phantom to study how precisely SPECT images reflect tracer uptake in myocardial infarction. A defect with 20%, 40% or 60% of normal myocardial radioactivity was placed in the anterior or inferior wall of a myocardial phantom to simulate myocardial infarction. Lung radioactivity was kept at 10% or 30% of normal myocardial radioactivity. The count ratio on short-axis SPECT images was calculated using the circumferential profile curve analysis. The count ratios of 201TI and 99mTc SPECT images with an anterior wall defect was lower than the true radioactivity in the phantom. The count ratio on SPECT images with the inferior wall defect was greater than the true radioactivity for the 20% and 40% defects and lower for the 60% defect. SPECT images overestimated decreased perfusion in the anterior wall. SPECT images underestimated decreased perfusion for 20% and 40% perfusion defects in the inferior wall.


[Diagnostic thoracoscopy in mediastinal space-occupying lesions].
Thoracoscopy is a helpful and safe procedure for diagnosing a variety of mediastinal masses if adequate information cannot be obtained out due to biological risk or patient non-compliance. An explicit description of thoracoscopic technique is given along with case reports demonstrating the efficiency of the method.


Outcome of operative treatment in fresh lateral clavicular fracture.
23 fresh type II (Neer 1963) lateral clavicular fractures, were treated operatively. In 19 cases fixation was done with two Kirschner wires, in four cases plating was performed. The coracoclavicular ligament was left unsutured. The average follow-up period was 4.5 (1-12) years. In 22 cases out of 23 the subjective outcome was good or satisfactory. 22 fractures united and there were few complications.


Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy.
Though increasing understanding and remarkable clinical successes have been made, enormous challenges remain to be solved in the field of cancer immunotherapy. In this context, biomaterial-based immunomodulatory strategies are being developed to boost antitumor immunity. For the local immunotherapy, macroscale biomaterial scaffolds with 3D network structures show great superiority in the following aspects: facilitating the encapsulation, localized delivery, and controlled release of immunotherapeutic agents and even immunocytes for more efficient immunomodulation. The concentrating immunomodulation in situ could minimize systemic toxicities, but still exert abscopal effects to harness the power of overall anticancer immune response for eradicating malignancy. To promote such promising immunotherapies, the design requirements of macroscale 3D scaffolds should comprehensively consider their physicochemical and biological properties, such as porosity, stiffness, surface modification, cargo release kinetics, biocompatibility, biodegradability, and delivery modes. To date, increasing studies have focused on the relationships between these parameters and the biosystems which will guide/assist the 3D biomaterial scaffolds to achieve the desired immunotherapeutic outcomes. In this review, by highlighting some recent achievements, we summarized the latest advances in the development of various 3D scaffolds as niches for cancer immunotherapy. We also discussed opportunities, challenges, current trends, and future perspectives in 3D macroscale biomaterial scaffold-assisted local treatment strategies. More importantly, this review put more efforts to illustrate how the 3D biomaterial systems affect to modulate antitumor immune activities, where we discussed how significant the roles and behaviours of 3D macroscale scaffolds towards in situ cancer immunotherapy in order to direct the design of 3D immunotherapeutic.


Impact of a bladder scan protocol on discharge efficiency within a care pathway for ambulatory inguinal herniorraphy.
Postoperative urinary retention (POUR) is a common complication of ambulatory inguinal herniorraphy, with an incidence reaching 38%, and many surgeons require patients to void before discharge. This study aimed to assess whether the implementation of a bladder scan-based voiding protocol reduces the time until discharge after ambulatory inguinal herniorraphy without increasing the rate of POUR. As part of a perioperative care pathway, a protocol was implemented to standardize decision making after elective inguinal hernia repair (February 2012). Patients were assessed with a bladder scan, and those with <600 mL of urine were discharged home, whereas those with more than 600 mL of urine had an in-and-out catheterization before discharge. The patients received written information about urinary symptoms and instructions to present to the emergency department if they were unable to void at home. An audit of scheduled outpatient inguinal hernia repairs between October 2011 and July 2012 was performed. Comparisons were made using the t test, Fisher's exact test, and Wilcoxon rank sum test where appropriate. Statistical significance was defined a priori as a p value lower than 0.05. During the study period, 124 patients underwent hernia repair: 60 before and 64 after implementation of the protocol. The findings showed no significant differences in patient characteristics, laparoscopic approach (35 vs. 33%; p = 0.80), proportion receiving general anesthesia (70 vs. 73%; p = 0.67), or amount of intravenous fluids given (793 vs. 663 mL; p = 0.07). The proportion of patients voiding before discharge was higher after protocol implementation (73 vs. 89%; p = 0.02). The protocol had no impact on median time to discharge (190 vs. 205 min; p = 0.60). Only one patient in each group presented to the emergency department with POUR (2%). After ambulatory inguinal herniorraphy, implementation of a bladder scan-based voiding protocol did not result in earlier discharge. The incidence of POUR was lower than reported in the literature.


The Mustard procedure: a commentary.
The Mustard operation, first performed clinically in May, 1963, greatly improved the outlook for infants and children with transposition of the great arteries (TGA). The event stimulated widespread interest in the management of TGA and ultimately led to the return of the Senning repair and the development of Jatene's arterial repair. Although current results, particularly those with neonates, suggest that arterial repair may displace the Mustard operation, it remains a milestone in the history of TGA.


Impact of SNPs on methylation readouts by Illumina Infinium HumanMethylation450 BeadChip Array: implications for comparative population studies.
Infinium HumanMethylation 450 BeadChip Arrays by Illumina (Illumina HM450K) are among the most popular CpG microarray platforms widely used in biological and medical research. Several recent studies highlighted the potentially confounding impact of the genomic variation on the results of methylation studies performed using Illumina's Infinium methylation probes. However, the complexity of SNPs impact on the methylation level measurements (β values) has not been comprehensively described. In our comparative study of European and Asian populations performed using Illumina HM450K, we found that the majority of Infinium probes, which differentiated two examined groups, had SNPs in their target sequence. Characteristic tri-modal or bi-modal patterns of β values distribution among individual samples were observed for CpGs with SNPs in the first and second position, respectively. To better understand how SNPs affect methylation readouts, we investigated their impact in the context of SNP position and type, and of the Illumina probe type (Infinium I or II). Our study clearly demonstrates that SNP variation existing in the genome, if not accounted for, may lead to false interpretation of the methylation signal differences suggested by some of the Illumina Infinium probes. In addition, it provides important practical clues for discriminating between differences due to the methylation status and to the genomic polymorphisms, based on the inspection of methylation readouts in individual samples. This approach is of special importance when Illumina Infinium assay is used for any comparative population studies, whether related to cancer, disease, ethnicity where SNP frequencies differentiate the studied groups.


An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.
The dynamic, posttranslational modification of proteins with a small ubiquitin-like modifier (SUMO) tag has been recognized as an important cellular regulatory mechanism relevant to a number of cancers as well as normal embryonic development. As part of a program aimed toward the identification of inhibitors of SUMO-conjugating enzymes, we developed a microfluidic electrophoretic mobility shift assay to monitor sumoylation events in real time. We disclose herein the use of this assay to identify a cell-permeable compound capable of blocking the transfer of SUMO-1 from the E2 enzyme Ubc9 to the substrate. We screened a small collection of compounds and identified an oxygenated flavonoid derivative that inhibits sumoylation in vitro. Next, we carried out an in-depth mechanistic analysis that ruled out many common false-positive mechanisms such as aggregation or alkylation. Furthermore, we report that this flavonoid inhibits a single step in the sumoylation cascade: the transfer of SUMO from the E2 enzyme (Ubc9) thioester conjugate to the substrate. In addition to having a unique mechanism of action, this inhibitor has a discrete structure-activity relationship uncharacteristic of a promiscuous inhibitor. Cell-based studies showed that the flavonoid inhibits the sumoylation of topoisomerase-I in response to camptothecin treatment in two different breast cancer cell lines, while isomeric analogs are inactive. Importantly, this compound blocks sumoylation while not affecting ubiquitylation in cells. This work identifies a point of entry for pharmacologic inhibition of the sumoylation cascade and may serve as the basis for continued study of additional pharmacophores that modulate SUMO-conjugating enzymes such as Ubc9.


Optimized inversion-prepared gradient echo imaging.
To implement a method using an extended phase graph (EPG)-based simulation to optimize inversion-prepared gradient echo sequences with respect to signal and contrast within the shortest acquisition time. A critical issue in rapid gradient-echo imaging is the effect of residual transverse magnetization between consecutive data acquisition windows. Various spoiling schemes have been proposed to mitigate this problem, and while spoiling is often considered to be perfect, imaging can be more truthfully described using the EPG. An EPG-based simulation is used to analyze and predict the image signal and contrast to serve as a basis for sequence optimization. Fourteen biological phantom experiments and five brain imaging experiments on each of five healthy volunteers was performed to validate and verify the accuracy of the EPG-based simulation. In addition, two experiments on an in-cranial cadaver brain were performed to show the ability of the proposed method for improving overall image quality. From the experiment results, it is demonstrated that optimization of 3D magnetization-prepared rapid gradient-echo imaging sequences can be performed with an EPG-based simulation to manipulate the sequence parameters for generating images with highly specific signal and contrast characteristics for quantitative T1-weighted human brain imaging.


A scaling model for dichotomous branching processes.
We derive an affine scaling law for dichotomous branching processes in biological systems. An application to the human bronchial tree demonstrates good agreement with experimental results.


Machine learning assisted remote forestry health assessment: a comprehensive state of the art review.
Forests are suffering water stress due to climate change; in some parts of the globe, forests are being exposed to the highest temperatures historically recorded. Machine learning techniques combined with robotic platforms and artificial vision systems have been used to provide remote monitoring of the health of the forest, including moisture content, chlorophyll, and nitrogen estimation, forest canopy, and forest degradation, among others. However, artificial intelligence techniques evolve fast associated with the computational resources; data acquisition, and processing change accordingly. This article is aimed at gathering the latest developments in remote monitoring of the health of the forests, with special emphasis on the most important vegetation parameters (structural and morphological), using machine learning techniques. The analysis presented here gathered 108 articles from the last 5 years, and we conclude by showing the newest developments in AI tools that might be used in the near future.


Spatiotemporal characteristics of surface water resources in the Tibetan plateau: Based on the produce water coefficient method considering snowmelt.
The Tibetan Plateau (TP), with its widely distributed cryosphere elements and the source of 12 major rivers, is a strategic area for Asian water resource generation, storage, and migration. Because of the unique surface water resources (SWR) characteristics, multi-phase and multiple sources, the hydrological process here is extremely complex. Coupled with the lack of measured data, the SWR in the TP has not been quantified refinedly. Thus, an improved large-scale SWR assessment method was proposed based on the produce water coefficient (PWC) method considering snowmelt. It overcomes the challenge of scarcity of data on ungauged regions. As climate changes, long-sequence dynamic evaluation of SWR can be achieved refinedly. As a result, the datasets of the amount of SWR of the level 4 water resources zones (WRZ) in the TP from 1956 to 2018 were obtained by calculating the PWC and snowmelt. Then spatiotemporal characteristics of SWR in the TP were analyzed. The results showed that the annual average SWR of the TP has been increasing over the past 60 years. Affected by climate change, the SWR in the Eastern TP increased, while the SWR in the Western TP (western part of the Karakoram Mountains) decreased significantly. The findings could be beneficial for water resource security and sustainable development in Asia. This revised method, which well avoided the misestimation of classical methods, could be used to evaluate the large-scale SWR for cold and ungauged regions.


Differential effects of out-of-hospital interventions on short- and long-term survival after cardiopulmonary arrest.
The aim of this study was to describe the relationship between prehospital clinical variables, interventions and survival time after cardiac arrest and to determine whether various factors affect the risk of death differently at early and late time periods. Time-to-death (days) after collapse was identified using the paramedic record, the social security death index or obituaries for adult (> or =18 years) out-of-hospital cardiac arrest (OOHCA) cases from Pittsburgh, Pennsylvania between 1998 and 2002. Clinical prehospital variables included age of patient, sex, witnessed collapse, bystander CPR, use of an automated external defibrillator (AED), initial ECG rhythm, medications and response time intervals. We used Cox regression with time varying coefficients to describe the effects of each covariate separately upon short-term (on day 1) and long-term (after day 1) survival. Of 1496 adult patients, overall mortality was 89.5%. The majority (75%) of deaths occurred on day 1. Of the 1339 deaths, 1213 (90.6%) occurred by day 3, 1272 (95.0%) occurred by day 7 and 1299 (97.0%) occurred by day 14. Witnessed collapse (hazard ratio 0.85; 95% CI: 0.75-0.97) or the use of epinephrine (adrenaline) (1.57; 1.20-2.07), lidocaine (0.78; 0.66-0.91) or dopamine (0.75; 0.56-1.00) were independently associated with risk of death on day 1 (day of collapse). Epinephrine use (1.84; 1.23-2.78) and age (1.02; 1.01-1.03) were independently associated with risk of death after day 1. The proportional hazards assumption was satisfied. Survival after out-of-hospital cardiac was characterized by a large number of deaths on day 1. Most subsequent deaths were identified within 14 days after collapse. Prehospital factors have markedly different relationships with short- and long-term survival. Linkage between prehospital intervention and short- and long-term outcomes must consider the survival time characteristics of this population.


Perfectionism, Self-Efficacy Components, and Metacognitive Listening Strategy Use: A Multicategorical Multiple Mediation Analysis.
The present investigation examined the effect of perfectionism on metacognitive listening strategy (MLS) use through the components of self-efficacy (initiative, effort, and persistence) among a sample of 117 Iranian English as a Foreign Language university students. Cluster analysis was utilized to identify the perfectionistic clusters. The resulting analysis yielded a three-cluster solution (adaptive, maladaptive, and non-perfectionist). Multicategorical multiple mediation analysis was then used to explore the relative direct, indirect, and total effects and to test the postulated hypotheses of the study. Results indicated that adaptive perfectionism was associated with higher levels of effort and persistence, leading to greater MLS use. Regarding the initiative subscale, no significant differences were observed among the three perfectionist groups. Maladaptive perfectionists showed high levels of effort investment but not persistence. Mediation analysis did not support self-efficacy components as the mediators of the relationship between perfectionism and MLS use. Among self-efficacy components, only effort exerted a positive effect on MLS use. Results are discussed in terms of implications for future research and classroom practice.


Serum uric acid and lipid profiles in sporadic Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system. Brain lipid homeostasis and oxidative stress seem to play an important role in the disease pathogenesis. But little was known whether serum lipids and uric acid (a natural antioxidant) levels changed in patients with prion disease. Here we retrospectively reviewed and compared the serum lipids and uric acid levels of 19 probable sporadic CJD patients and 26 healthy control subjects. We found that the serum uric acid levels in sporadic CJD patients were significantly lower than that in controls (P=0.01). Serum triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and apolipoprotein A1 (ApoA1) were similar in sporadic CJD patients and controls. However, LDL/HDL ratio was lower in sporadic CJD patients (P=0.003). The low serum uric acid and LDL/HDL ratio levels in sporadic CJD indicate that dysfunction in the lipid homeostasis and oxidative stress is associated with sporadic prion disease.


A comment on the 1990 recommendations of the ICRP.
ICRP Publication 60 recommends a change relating to the numerical assessment of radiation quality in radiation protection. The quality factor, Q, is to be replaced by "radiation weighting factors," WR, and the quantity "effective dose equivalent" is to be supplanted by "effective dose." Reasons are given why it is virtually impossible to measure this quantity and why it appears unavoidable that practical measurements will continue to be based on the current system. No sensible justification was provided for the proposed change, which is likely to cause confusion.


Inter-observer variability in systematic nodal dissection: comparison of European and Japanese nodal designation.
Systematic nodal dissection is accepted as an important component of the intrathoracic staging of patients undergoing thoracotomy for lung cancer. Several lymph node maps have been proposed in an attempt to ensure uniformity in designating lymph node stations. The Japan Lung Cancer Society has published detailed definitions for each nodal station adopting the Naruke map. However, since these definitions had not been interpreted into other languages, they have not been universally accepted. The objective of this study was to assess the inter-observer variability in the interpretation of lymph node stations. A total of 424 lymph node stations were removed from 41 patients undergoing thoracotomy for non-small cell lung cancer. All nodal stations were labeled using the Naruke map. As each station was excised, it was designated in a blind fashion by one of two surgeons trained in the UK and one surgeon trained in Japan. The designation accorded to each nodal station was analyzed. The total concordance was 68.5% (right side 67.0%, left side 69.9%). The concordance rate for individual nodal stations varied from 0% to 100%. Considerable discordance existed between the Japanese and European surgeons in the designation of nodal stations 2, 4, 8 and N1 station 12. In 14 (34.1%) patients, discordance in the labeling of lymph nodes led to disease being categorized as N1 by one observer, whereas the other considered the same nodes to be N2. Considerable discordance in the designation of nodal station has been demonstrated. We would expect similar inter-observer variability elsewhere between surgeons, institutions, or countries. More detailed nodal charts and precise, easily understood definitions of nodal stations are needed for intrathoracic staging. The first English version of the Japan Lung Cancer Society staging manual goes some way to address this.


The membrane proximal disulfides of the EGF receptor extracellular domain are required for high affinity binding and signal transduction but do not play a role in the localization of the receptor to lipid rafts.
The EGF receptor is a transmembrane receptor tyrosine kinase that is enriched in lipid rafts. Subdomains I, II and III of the extracellular domain of the EGF receptor participate in ligand binding and dimer formation. However, the function of the cysteine-rich subdomain IV has not been elucidated. In this study, we analyzed the role of the membrane-proximal portion of subdomain IV in EGF binding and signal transduction. A double Cys-->Ala mutation that breaks the most membrane-proximal disulfide bond (Cys600 to Cys612), ablated high affinity ligand binding and substantially reduced signal transduction. A similar mutation that breaks the overlapping Cys596 to Cys604 disulfide had little effect on receptor function. Mutation of residues within the Cys600 to Cys612 disulfide loop did not alter the ligand binding or signal transducing activities of the receptor. Despite the fact that the C600,612A EGF receptor was significantly impaired functionally, this receptor as well as all of the other receptors with mutations in the region of residues 596 to 612 localized normally to lipid rafts. These data suggest that the disulfide-bonded structure of the membrane-proximal portion of the EGF receptor, rather than its primary sequence, is important for EGF binding and signaling but is not involved in localizing the receptor to lipid rafts.


Fluorinated photoremovable protecting groups: the influence of fluoro substituents on the photo-Favorskii rearrangement.
To further explore the nature of the photo-Favorskii rearrangement and its commitment to substrate photorelease from p-hydroxyphenacyl (pHP), an array of ten new fluorinated pHP gamma-aminobutyric acid (GABA) derivatives was synthesized and photolyzed. The effects of fluorine substitution on the chromophore and the photophysical and photochemical properties of these new chromophores were shown to be derived primarily from the changes in the ground state pK(a) of the phenolic groups. The quantum yields and rate constants for release are clustered around Phi(dis) = 0.20 +/- 0.05 and k(r) = 8 +/- 7 x 10(7) s(-1) (H2O), respectively. The triplet lifetimes of the pHP GABA derivatives were concentrated in the range of 0.4-6.0 ns (H2O). The corresponding deprotonated conjugate bases displayed reduced efficiencies by 50% or more (one exception) and exhibited a weak fluorescence in pH 8.2 buffer. Pump-probe spectroscopy studies have further defined the rates of intersystem crossing and the lifetimes of the reactive triplet state of the fluoro pHP chromophore.


CRTAC1 enhances the chemosensitivity of non-small cell lung cancer to cisplatin by eliciting RyR-mediated calcium release and inhibiting Akt1 expression.
Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in patients with non-small cell lung cancer (NSCLC). Here, our results obtained from analyses of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca2+ levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation and, in turn, enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca2+-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.


[Peculiar features of the diagnosis and operative treatment of patients with post-infarction aneurysm of the left ventricle complicated by thrombosis].
Echocardiography and contrast ventriculography are of critical importance in diagnosing thrombi, only in 7.6% of cases echocardiography failed to diagnose thrombosis of the aneurysm cavity. The data of ventriculography thrombi were found but in 84.3% of all the patients with post-infarction aneurysm of the left ventricle (PALV) complicated by thrombosis. The preoperative preparation of patients with PALV included a regulation of the coagulating system using plasmapheresis and plasmathrombocytopheresis. During operations of patients with PALV complicated by a thrombus, following opening the aneurysm cavity, a wide turunda was laid under the thrombus to prevent embolism. These new measures reduced lethality of thromboembolic complications to 0.24%.


18F-FDG-PET metabolic metrics and International Prognostic Score for risk assessment in HIV-infected patients with Hodgkin lymphoma.
Baseline metabolic metrics on fluorine-18-fluorodeoxyglucose PET (F-FDG PET) have prognostic value in Hodgkin lymphoma. International Prognostic Score (IPS) is used in the risk stratification of Hodgkin lymphoma. We compared the metabolic indices in HIV-infected and the IPS in HIV-infected and uninfected patients with Hodgkin lymphoma. We retrospectively reviewed the data of HIV-infected and HIV-uninfected patients with classic Hodgkin lymphoma who had F-FDG PET for staging and compared the maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups. We also compared the IPS and other prognostic indicators and correlated them with the metabolic indices in the two groups. We studied 160 patients, which included 57 patients who were infected with HIV. The mean age was 33.84±11.88 years, with 38% (n=61) being female. The median cluster of differentiation 4 count and HIV viral load were 259 cells/mm and 4837.50 copies/ml, respectively. No significant difference in maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups was found. Among the seven parameters of the IPS, only male sex (HIV-uninfected group higher, P=0.005) and serum albumin less than 4 g/dl were significantly different. The other parameters were not significantly different between the two groups. Other prognostic indicators including bulky disease, extranodal involvement, and the number of nodal groups involved were not significantly different between the two groups. There was no significant difference in F-FDG metabolic parameters, IPS, and other risk indicators between HIV-infected and HIV-uninfected patients with Hodgkin lymphoma.


Inhibition of tissue repair by spironolactone: role of mineralocorticoids in fibrous tissue formation.
Mineralocorticoids have been implicated in promoting fibrous tissue formation in various organs. In the present study, we sought to address the potential contribution of mineralocorticoids to fibrous tissue formation using a skin pouch model which has proved valuable for the analysis of inflammatory and wound healing responses. Skin pouches were induced in rats by administration of a phorbol ester, croton oil (0.5 ml of a 1% solution). After 2 weeks, rats were killed and intact pouch tissue collected. Pouch weights of control and aldosterone-treated (0.75 microg/h via osmotic minipump) rats were similar (3.33 +/- 0.44 g vs. 3.70 +/- 0.28 g respectively). However, pouch weights were reduced by more than 50% in spironolactone-treated (25 mg/day powdered in food) animals (1.62 +/- 0.22 g and 1.27 +/- 0.23 g respectively in aldosterone and spironolactone alone groups). To ascertain the effects of different treatments on collagen accumulation, hydroxyproline concentration was measured. Compared with controls, hydroxyproline concentration was significantly reduced following spironolactone treatment (17.1 +/- 0.08 vs. 7.5 +/- 2.0 microg/mg dry wt, respectively, p < 0.01). This response to spironolactone was negated by coadministration of aldosterone (hydroxyproline concentration was 18.6 +/- 2.1 microg/mg dry wt). Following bilateral adrenalectomy, spironolactone reduced pouch weight and hydroxyproline concentration, which was not the case for adrenalectomy alone. Two week aldosterone administration in uninephrectomized rats on high salt diet was deemed ineffective in modulating pouch development (pouch wet wts were 3.48 +/- 0.4 g vs. 3.00 +/- 0.19 g in controls and aldosterone-treated rats, respectively). Mineralocorticoid receptor expression in pouch tissue was demonstrated by RT/PCR. Furthermore, NADP+-dependent 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity was detected in pouch tissue, together with lower levels of NAD+-dependent 11beta-HSD2. Spironolactone (p < 0.05) significantly reduced 11beta-HSD1 activity compared with controls. Thus, fibrous tissue possesses requisite components of MC action, and antagonism of mineralocorticoid receptors by spironolactone attenuates its formation. Pouch formation is under the influence of circulating MC and, we would like to propose, is also mediated through corticosteroids generated de novo at the site of tissue repair.


Associations Between Cognitive Function and Levels of Glutamatergic Metabolites and Gamma-Aminobutyric Acid in Antipsychotic-Naïve Patients With Schizophrenia or Psychosis.
Abnormal glutamate and GABA (gamma-aminobutyric acid) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naïve patients. In total, 56 antipsychotic-naïve patients with schizophrenia or psychotic disorder and 51 healthy control subjects underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (Glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and Glx levels in left thalamus. The cognitive domains of attention, working memory, and IQ were assessed. The whole group of antipsychotic-naïve patients had lower levels of GABA in dorsal ACC (p = .03), and the subgroup of patients with a schizophrenia diagnosis had higher glutamate levels in thalamus (p = .01), but Glx levels in dorsal ACC and thalamus did not differ between groups. Glx levels in dorsal ACC were positively associated with working memory (logarithmically transformed: b = -.016 [higher score indicates worse performance], p = .005) and attention (b = .056, p = .035) in both patients and healthy control subjects, although the association with attention did not survive adjustment for multiple comparisons. The findings suggest a positive association between glutamatergic metabolites and cognitive function that do not differ between patients and healthy control subjects. Moreover, our data indicate that decreased GABAergic levels in dorsal ACC are involved in schizophrenia and psychotic disorder, whereas increased glutamate levels in thalamus seem to be implicated in schizophrenia pathophysiology. The findings imply that first-episode patients with cognitive deficits may gain from glutamate-modulating compounds.


Adsorption of small biological molecules on silica from diluted aqueous solutions: quantitative characterization and implications to the Bernal's hypothesis.
To describe quantitatively the adsorption of prebiotically important compounds of low molecular weight (amino acids, short linear peptides, cyclic dipeptides, the Krebs's cycle and other carboxylic acids, nucleosides and related phosphates) on silica surface from diluted neutral aqueous solutions, equilibrium constants (K) and free energies (-delta G) of adsorption were determined from the retention values measured by means of high-performance liquid chromatography on a silica gel column and from the isotherms measured under static conditions. For most carboxylic acids (including amino acids and linear peptides) -delta G values were negative and K < 1, thus showing very weak adsorption. Cyclic dipeptides (2,5-piperazinediones) exhibited higher adsorbability; -delta G > 0 and K > 1 were found for most of them. Influence of the structure of alpha-substituent on the adsorbability is analyzed. A linear dependence of -delta G on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the row from glycine to triglycyl glycine. The adsorption of nucleosides and their phosphates is characterized by much higher K and -delta G values (of the order of 10(2) and 10(4), respectively). The adsorption data available from our work and literature are summarized and discussed with implications to the Bernal's hypothesis on the roles of solid surfaces in the prebiotic formation of biopolymers from monomeric 'building blocks'.


Understanding the role of embarrassment in gynaecological screening: a qualitative study from the ASPIRE cervical cancer screening project in Uganda.
To define embarrassment and develop an understanding of the role of embarrassment in relation to cervical cancer screening and self-collected human papillomavirus (HPV) DNA testing in Uganda. Cross-sectional, qualitative study using semistructured one-to-one interviews and focus groups. 6 key-informant health workers and 16 local women, purposively sampled. Key informant inclusion criteria: Ugandan members of the project team. Focus group inclusion criteria: woman age 30-69 years, Luganda or Swahili speaking, living or working in the target Ugandan community. unwillingness to sign informed consent. Primary and tertiary low-resource setting in Kampala, Uganda. In Luganda, embarrassment relating to cervical cancer is described in two forms. 'Community embarrassment' describes discomfort based on how a person may be perceived by others. 'Personal embarrassment' relates to shyness or discomfort with her own genitalia. Community embarrassment was described in themes relating to place of study recruitment, amount of privacy in dwellings, personal relationship with health workers, handling of the vaginal swab and misunderstanding of HPV self-collection as HIV testing. Themes of personal embarrassment related to lack of knowledge, age and novelty of the self-collection swab. Overall, embarrassment was a barrier to screening at the outset and diminished over time through education and knowledge. Fatalism regarding cervical cancer diagnosis, worry about results and stigma associated with a cervical cancer diagnosis were other psychosocial barriers described. Overcoming psychosocial barriers to screening can include peer-to-peer education, drama and media campaigns. Embarrassment and other psychosocial barriers may play a large role at the onset of a screening programme, but over time as education and knowledge increase, and the social norms around screening evolve, its role diminishes. The role of peer-to-peer education and community authorities on healthcare cannot be overlooked and can have a major impact in overcoming psychosocial and social barriers to screening.


Predictors, prevalence, and patterns of cyberbullying among school-going children and adolescents.
Cyberbullying is a major health issue across the globe as it affects the mental health and well-being of the victims, especially children and adolescents, since there is a dearth of studies in the Indian setting. This study aimed to understand the predictors, patterns, prevalence, mental health problems, and coping of cyberbullying among adolescents. The study adopted a cross-sectional explorative design with 484 adolescents studying in 8th to 12th standards recruited through convenient sampling. The Cyberbullying Online Aggression Survey Instrument (COASI), Strength and Difficulties Questionnaire (SDQ), Coping with Cyberbullying Questionnaire (CWCBQ), and Internet usage pattern were administered to collect the data. Multinomial logistic regression was used to find the predictors of the only cyber-victim, only cyber-offending, and both cyber-victim and cyber-offending. The findings showed that 14.5% of teenagers were victims of cyberbullying, 5.8% were offenders, and 13.8% were both victims and offenders. The predictors for "cyber-victimization" were father's education and religion. The predictors of "cyber-offenders" were grade, Internet usage, and father's occupation. Adolescents identified as both cyber-victims and cyber-offenders were predicted by gender, grade, religion, and father's employment. The study indicated a high prevalence of cyber-victimization and cyber-offending among adolescents with many psychosocial risk factors. The findings highlighted the need for a school-based cyberbullying intervention program to address the issues using a whole-school approach.


Functional inhibition of MEF2 by C/EBP is a possible mechanism of leukemia development by CEBP-IGH fusion gene.
CEBPA-IGH, a fusion gene of the immunoglobulin heavy-chain locus (IGH) and the CCAAT enhancer-binding protein α (C/EBPα) gene, is recurrently found in B-ALL cases and causes aberrant expression of C/EBPα, a master regulator of granulocyte differentiation, in B cells. Forced expression of C/EBPα in B cells was reported to cause loss of B-cell identity due to the inhibition of Pax5, a master regulator of B-cell differentiation; however, it is not known whether the same mechanism is applicable for B-ALL development by CEBPA-IGH. It is known that a full-length isoform of C/EBPα, p42, promotes myeloid differentiation, whereas its N-terminal truncated isoform, p30, inhibits myeloid differentiation through the inhibition of p42; however, the differential role between p42 and p30 in ALL development has not been clarified. In the present study, we examined the effect of the expression of p42 and p30 in B cells by performing RNA-seq of mRNA from LCL stably transfected with p42 or p30. Unexpectedly, suppression of PAX5 target genes was barely observed. Instead, both isoforms suppressed the target genes of MEF2 family members (MEF2s), other regulators of B-cell differentiation. Similarly, MEF2s target genes rather than PAX5 target genes were suppressed in CEBP-IGH-positive ALL (n = 8) compared with other B-ALL (n = 315). Furthermore, binding of both isoforms to MEF2s target genes and the reduction of surrounding histone acetylation were observed in ChIP-qPCR. Our data suggest that the inhibition of MEF2s by C/EBPα plays a role in the development of CEBPA-IGH-positive ALL and that both isoforms work co-operatively to achieve it.


Superoxide-independent reduction of vanadate by rat liver microsomes/NAD(P)H: vanadate reductase activity.
It has been reported that vanadate-stimulated oxidation of NAD(P)H by microsomal systems can proceed anaerobically, in contrast to the general notion that the oxidation proceeds exclusively by an O(2-)-dependent free radical chain mechanism. The current study indicates that microsomal systems are endowed with a vanadate-reductase property, involving a NAD(P)H-dependent electron transport cytochrome P450 system. Our ESR measurements demonstrated the formation of a vanadium(IV) species in a mixture containing vanadate, rat liver microsomes, and NAD(P)H. This vanadium(IV) species was identified as the vanadyl ion (VO2+) by comparison with the ESR spectrum of VOSO4. The initial rate of vanadium(IV) formation depends linearly on the concentration of microsomes. The Michaelis-Menten constants were found to be: km = 1.25 mM and Vmax = 0.066 mumol (min)-1 (mg microsomes)-1, respectively. Pretreatment of the microsomes with carbon monoxide or K3Fe(CN)6 reduced vanadium(IV) generation, suggesting that the NAD(P)H-dependent electron transport cytochrome P450 system plays a significant role in the microsomal reduction of vanadate. Measurements under argon or in the presence of superoxide dismutase caused only minor (less than 10%) reductions in vanadium(IV) generation. The VO2+ species was also detected in NAD(P)H oxidation by fructose plus vanadate, a reaction known to proceed via an O(2-)-mediated chain mechanism. However, the amount of vanadium(IV) generated by this reaction was an order of magnitude smaller than that by the microsomal system and was inhibitable by superoxide dismutase, affirming the conclusion that the microsomal/NAD(P)H system is endowed with the (O(2-)-independent) vanadium(V) reductase property.


Gastric and esophageal cancers incidence mapping in golestan province, iran: using bayesian-gibbs sampling.
Recent studies of esophageal cancer (EC) and gastric cancer (GC) have been reported to have high incidence rates of these cancers in Golestan Province of Iran. The present study describes the geographical patterns of EC and GC incidence based on cancer registry data and display statistically significant regions within this province. In order to map the distribution of upper gastrointestinal cancer, relative risk (RR) were calculated. Therefore, to estimate a more reliable RR, Poisson regression models were used. The adjusted models (adjusted to urban-rural area, sex, and grouped age proportion) were utilized. We considered two-component random effects for each observation, an unstructured (noncorrelated) and a group of "neighbor" (correlated) heterogeneities. We estimated the model parameters using Gibbs sampling and empirical Bayes method. We used EC and GC data that were registered with Golestan Research Center of Gastroenterology and Hepatology in the years 2004-2008. The EC and GC maps were drawn for 2004-2008 in the province. Kalaleh and Minoodasht counties have a high RR of EC and GC in the years of study. In almost all years, the areas with a high RR were steady. The EC and GC maps showed significant spatial patterns of risk in Golestan province of Iran. Further study is needed to multivariate clustering and mapping of cancers RRs with considering diet and socioeconomic factors.


[Evaluation of the new German measles protection act: An online survey].
The current COVID-19 pandemic reveals the dangerousness of infectious diseases and the threats we face. Often however, effective vaccinations are carried out insufficiently. In March 2020, the German measles protection law was introduced to raise the level of population (herd) immunity to over 95 %. An anonymous online survey was conducted among the population on the Measles Protection Act with self-declarations on measles vaccination/illness of participants and their children and evaluation of various sanctions. 1,594 adults participated. 19.3 % were affected by the law. Of these, only 77.5 % were immune to measles, 14.0 % wanted to be fully vaccinated when the law came into force, which would lead to 91.5 % immunity. Assuming that participants with unclear vaccination status or measles disease are immune, an immunity of>95 % can be achieved. 86.4 % of the children (aged 2 to 17 years) had developed immunity. Parents' willingness to have their children vaccinated because of the sanctions provided for in the Measles Protection Act was only 0.8 %. The level of immunity to measles in adults and children was under 95 % in our study. The sanctions of the Measles Protection Act are a greater incentive for adults to undergo measles vaccination than for parents. Strategies to increase immunity with the target group of parents should continue to be pursued.


Deep learning-enhanced radiomics for histologic classification and grade stratification of stage IA lung adenocarcinoma: a multicenter study.
Preoperative prediction models for histologic subtype and grade of stage IA lung adenocarcinoma (LUAD) according to the update of the WHO Classification of Tumors of the Lung in 2021 and the 2020 new grade system are yet to be explored. We aim to develop the noninvasive pathology and grade evaluation approach for patients with stage IA LUAD via CT-based radiomics approach and evaluate their performance in clinical practice. Chest CT scans were retrospectively collected from patients who were diagnosed with stage IA LUAD and underwent complete resection at two hospitals. A deep learning segmentation algorithm was first applied to assist lesion delineation. Expansion strategies such as bounding-box annotations were further applied. Radiomics features were then extracted and selected followed by radiomics modeling based on four classic machine learning algorithms for histologic subtype classification and grade stratification. The area under the receiver operating characteristic curve (AUC) was used to evaluate model performance. The study included 294 and 145 patients with stage IA LUAD from two hospitals for radiomics analysis, respectively. For classification of four histological subtypes, multilayer perceptron (MLP) algorithm presented no annotation strategy preference and achieved the average AUC of 0.855, 0.922, and 0.720 on internal, independent, and external test sets with 1-pixel expansion annotation. Bounding-box annotation strategy also enabled MLP an acceptable and stable accuracy among test sets. Meanwhile, logistic regression was selected for grade stratification and achieved the average AUC of 0.928, 0.837, and 0.748 on internal, independent, and external test sets with optimal annotation strategies. DL-enhanced radiomics models had great potential to predict the fine histological subtypes and grades of early-stage LUADs based on CT images, which might serve as a promising noninvasive approach for the diagnosis and management of early LUADs.


Conidial heat resistance of various strains of the food spoilage fungus Paecilomyces variotii correlates with mean spore size, spore shape and size distribution.
Contamination by spores is often the cause of fungal food spoilage. Some distinct strains of the food spoilage fungus Paecilomyces variotii are able to produce airborne conidia that are more heat-resistant than similar species. These ellipsoid asexual spores can vary in size between strains, but also within strains. Here, we compared four measurement techniques to measure conidia size and distribution of five heat-sensitive and five heat-resistant P. variotii strains. Light microscopy (LM), Scanning Electron Microscopy (SEM) and Coulter Counter (CC) were used to measure and compare the spherical equivalent diameter, while CC and flow cytometry were used to study spore size distributions. The flow cytometry data was useful to study spore size distributions, but only relative spore sizes were obtained. There was no statistic difference between the method used of spore size measurement between LM, SEM and CC, but spore size was significantly different between strains with a 2.4-fold volume difference between the extremes. Various size distribution and shape parameters were correlated with conidial heat resistance. We found significant correlations in mean spore size, aspect ratio, roundness and skewness in relation to heat resistance, which suggests that these parameters are indicative for the conidial heat resistance of a P. variotii strain.


Quantitative morphologic study of intimal thickening at the human carotid bifurcation: I. Axial and circumferential distribution of maximum intimal thickening in asymptomatic, uncomplicated plaques.
The spatial distribution of intimal thickening was determined for each of 42 carotid bifurcations removed at autopsy from patients with no clinical or anatomic evidence of cerebrovascular disease. Both right and left specimens were available for six of the individuals. Each bifurcation was removed intact and included a 1.5-2.9-cm length of the common carotid artery and a 1.5-2.5-cm length of the internal carotid artery. The specimens were restored to in situ length, fixed under conditions of controlled-pressure perfusion at 100 mmHg, filled with a radio-opaque mixture, radiographed and sectioned at 0.5-cm intervals. Computer assisted contour tracing of projected images of histologic sections was used to determine intimal thickness, intimal cross sectional area and lumen area within each of eight equal 45 degrees polar sectors with 0 degree indexed at the flow divider, 90 degrees at the outside wall, 180 degrees opposite the flow divider and 270 degrees at the inner side wall. Intima occupied 0.9-42% of the area encompassed by the internal elastic lamina, i.e. the potential lumen area if no intimal thickening were present, but there was no lumen narrowing on lateral X-ray projections. Intimal thickening was eccentric at each level of section but the circumferential location of maximum intimal thickness (MIT) shifted in a continuous helix from level to level. At the common carotid artery level 1.0 cm proximal to the bifurcation, MIT tended to be at the flow-divider side at 15 +/- 59 degrees. Immediately proximal to the flow divider, MIT was at the lateral side wall. In the mid-sinus region of the internal carotid artery MIT was opposite the flow divider at 179 +/- 64 degrees. At the distal internal carotid just beyond the sinus, MIT was at the inner side wall. The distal internal carotid was minimally involved or free of intimal thickening. Comparison of right and left bifurcations revealed that the helical spatial distribution of MIT was in mirror-image symmetry for the two sides. The findings correspond closely with previous demonstrations of a helical flow pattern in the region of the bifurcation. Although locations of MIT just proximal and just distal to the bifurcation are similar and tend to be at the 'far wall', individual differences in the shifts of MIT with axial location should be taken into account when sites of interrogation by non-invasive clinical methods are selected for detection of intimal thickening.


Risk factors for scholastic backwardness in children.
To identify the risk factors for scholastic backwardness in children. Children in the 6-12 year age group attending regular schools and referred to the child guidance clinic for scholastic backwardness. Tertiary care hospital in South India. Participants were compared with an age-and sex- matched group of children with good academic performance, to ascertain risk factors for scholastic backwardness. There were 75 boys and 35 girls in the study group. Among them 30 (27%) children had mental retardation, 39 (36%) had borderline intelligence and 12 (11%) had microcephaly. Undernutrition was noted in 36 (33%) children and 31 (28%) had stunted growth. 28 (26%) children had a history of chronic medical problems like epilepsy, bronchial asthma and congenital heart diseases. Visual, hearing and speech defects were present in 6 (6%), 5 (5%) and 12 (11%) children, respectively. Statistically significant differences were noted in the educational level and employment status of parents of children with scholastic backwardness and those with good academic performance. Social and family factors have a significant influence on the academic functioning of children.


Current topics in hearing research: Deafferentation and threshold independent hearing loss.
Hearing research findings in recent years have begun to change how we think about hearing loss and how we consider the risk of auditory damage from noise exposure. These findings include evidence of noise-induced cochlear damage in the absence of corresponding permanent threshold elevation or evidence of hair cell loss. Animal studies in several species have shown that noise exposures that produce robust but only temporary threshold shifts can permanently damage inner hair cell synaptic ribbons. This type of synaptic degeneration has also been shown to occur as a result of aging in animals and humans. The emergence of these data has motivated a number of clinical studies aimed at identifying the perceptual correlates associated with synaptopathy. The deficits believed to arise from synaptopathy include poorer hearing in background noise, tinnitus and hyperacusis (loudness intolerance). However, the findings from human studies have been mixed. Key questions remain as to whether synaptopathy reliably produces suprathreshold perceptual deficits or whether it serves as an early indicator of auditory damage with suprathreshold deficits emerging later as a function of further cochlear damage. Here, we provide an overview of both human and animal studies that explore the relationship among inner hair cell damage, including loss of afferent synapses, auditory thresholds, and suprathreshold measures of hearing.


A combination of liver fluke infection and traditional northeastern Thai foods associated with cholangiocarcinoma development.
Opisthorchis viverrini infection is one of the risk factors for cholangiocarcinoma (CCA) in northeast Thailand, a region with one of the highest reported incidence rates of CCA. The traditional practice of eating raw fish, repeated exposure to liver flukes, and consumption of nitrosamine-contaminated food are major risk factors for CCA. So far, there have been no reports about which northeastern traditional dishes may be involved in CCA development. The present study, thus, investigated the effects of traditional foods. It focused specifically on the consumption of fermented foods in combination with O. viverrini infection in hamsters. Syrian hamsters were divided into six groups: (i) normal hamsters, (ii) O. viverrini infection only and (iii)-(vi) O. viverrini infection plus fermented foods (pla som-fish fermented for 1 day), som wua-fermented beef, som phag-fermented vegetables, and pla ra-fish fermented for 6 months. Syrian hamster livers were used for analysis of histopathological changes through hematoxylin and eosin; Sirius Red; and immunohistostaining for cytokeratin-19, proliferating cell nuclear antigen, and CA19-9. Hamster sera were used for liver and kidney function tests. Results of all O. viverrini-infected groups and fermented food groups showed that histopathological changes consisted primarily of aggregations of inflammatory cells surrounding the hepatic bile duct, especially at the hilar region. However, there was a difference in virulence. Interestingly, aggregations of inflammatory cells, new bile duct formation, and fibrosis were observed in subcapsular hepatic tissue, which correlated to positive immunohistochemical staining and increased liver function test. The present study suggests that fermented food consumption can exacerbate cholangitis and cholangiofibrosis, which are risk factors for cholangiocarcinoma-associated opisthorchiasis.


Genetic analysis of a Piezo-like protein suppressing systemic movement of plant viruses in Arabidopsis thaliana.
As obligate intracellular phytopathogens, plant viruses must take advantage of hosts plasmodesmata and phloem vasculature for their local and long-distance transports to establish systemic infection in plants. In contrast to well-studied virus local transports, molecular mechanisms and related host genes governing virus systemic trafficking are far from being understood. Here, we performed a forward genetic screening to identify Arabidopsis thaliana mutants with enhanced susceptibility to a 2b-deleted mutant of cucumber mosaic virus (CMV-2aT∆2b). We found that an uncharacterized Piezo protein (AtPiezo), an ortholog of animal Piezo proteins with mechanosensitive (MS) cation channel activities, was required for inhibiting systemic infection of CMV-2aT∆2b and turnip mosaic virus tagged a green fluorescent protein (GFP) (TuMV-GFP). AtPiezo is induced by virus infection, especially in the petioles of rosette leaves. Thus, we for the first time demonstrate the biological function of Piezo proteins in plants, which might represent a common antiviral strategy because many monocot and dicot plant species have a single Piezo ortholog.


Home nutrition survey in the UK: the patient's perspective.
A detailed survey questionnaire compiled by the executive committee of Patients on Intravenous and Nasogastric Nutrition Therapy (PINNT) was circulated in November 1991 to the postal addresses of all full (patient) members of PINNT in the UK. The objective of the survey was to identify current practices and problems of home nutrition support as seen from the patients perspective. 128 questionnaires were distributed. 87 (68%) analysable questionnaires were completed and returned. 77 were for parenteral nutrition (HPN) patients and 10 for patients on enteral nutrition (HEN). Areas of concern for patients include the practicalities of administration of lipid and additives, and problems associated with the appearance of air in infusion bags. Although most patients appeared happy with the home nutrition support services 18% commented on particular negative aspects. This survey highlights such areas which may not be identified during routine patient/clinician contact.


Juvenile and adult olfactory ensheathing cells bundle and myelinate dorsal root ganglion axons in culture.
Olfactory ensheathing cells (OEC), which normally associate closely with but do not myelinate axons in situ, myelinate axons in the adult mammalian spinal cord. They are of clinical interest as candidate cells for autologous transplantation but the ability of OEC to myelinate axons in vitro has been controversial. To clarify this issue, we isolated OEC from olfactory bulbs (OB) of juvenile and adult rats expressing GFP and analyzed their ability to myelinate axons. Using a well-defined assay for myelination of dorsal root ganglia (DRG) axons in culture, we found that OEC from juvenile pups associated with and then myelinated DRG axons. OEC assembled into bundles with the axons by 1week and required more than a week before myelination on axons was detected. In contrast, rat Schwann cells did not bundle axons and they formed P0(+) and MBP(+) myelin segments after as little as 1week. Most of the OEC in culture exhibited staining for calponin, a marker that was not found on Schwann cells in culture, whereas in both OEC and Schwann cell populations nearly all cells were positive for p75NTR and GFAP. These results confirm previous reports showing only subtle immunological differences between Schwann cells and OEC. Besides differences in the rate of myelination, we detected two additional functional differences in the interactions of OEC and Schwann cells with DRG axons. First, the diameter of OEC generated myelin was greater than for Schwann cell myelin on DRG axons. Second, OEC but not Schwann cells myelinated DRG axons in the absence of vitamin C. OEC isolated from adult OB were also found to bundle and myelinate DRG axons but the latter occurred only after incubation times of at least 3weeks. The results indicate that adult OEC require longer incubation times than juvenile OEC to myelinate axons and suggest that patterns of myelination by OEC and Schwann cells are distinguishable at least on axons in vitro. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.


[Nebulization in acute asthma. Association of an atropine and a beta2-sympathomimetic].
Nebulization is a basic treatment for the management of severe acute asthma. Three mechanisms are involved in bronchial obstruction: bronchospasms, inflammation and an increase in bronchial secretions. Combination therapy including beta 2-sympatheticomimetic and synthetic atropinic drugs is strongly synergistic. In a French multicenter trial including 45 adult patients presenting with asthma, combination of nebulized Berotec and Atrovent was studied. It proved to be efficacious in two thirds of the patients. Results were even better for younger patients whose initial peak flow rate was high. Tolerance to this combination therapy was as good as that to beta 2-sympatheticomimetic monotherapy.


Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice.
Methods for determining cost-effectiveness of different treatments are well established, unlike appraisal of non-drug interventions, including novel diagnostics and biomarkers. The authors develop and validate a new health economic model by comparing cost-effectiveness of tuberculin skin test (TST); blood test, interferon-gamma release assay (IGRA) and TST followed by IGRA in conditional sequence, in screening healthcare workers for latent or active tuberculosis (TB). The authors focus on healthy life years gained as the benefit metric, rather than quality-adjusted life years given limited data to estimate quality adjustments of life years with TB and complications of treatment, like hepatitis. Healthy life years gained refer to the number of TB or hepatitis cases avoided and the increase in life expectancy. The authors incorporate disease and test parameters informed by systematic meta-analyses and clinical practice. Health and economic outcomes of each strategy are modelled as a decision tree in Markov chains, representing different health states informed by epidemiology. Cost and effectiveness values are generated as the individual is cycled through 20 years of the model. Key parameters undergo one-way and Monte Carlo probabilistic sensitivity analyses. Screening healthcare workers in secondary and tertiary care. IGRA is the most effective strategy, with incremental costs per healthy life year gained of £10 614-£20 929, base case, £8021-£18 348, market costs TST £45, IGRA £90, IGRA specificities of 99%-97%; mean (5%, 95%), £12 060 (£4137-£38 418) by Monte Carlo analysis. Incremental costs per healthy life year gained, a conservative estimate of benefit, are comparable to the £20 000-£30 000 NICE band for IGRA alone, across wide differences in disease and test parameters. Health gains justify IGRA costs, even if IGRA tests cost three times TST. This health economic model offers a powerful tool for appraising non-drug interventions in the market and under development.


Synaptic organisation of the pelvic ganglion in the guinea-pig.
A semi-quantitative electron-microscopic study of neuronal cell bodies, nerve profiles and synapses in the anterior pelvic ganglia of the guinea-pig has been carried out following in vivo labelling of adrenergic nerve endings with 5-hydroxydopamine. Ganglion cells of three main types have been distinguished: 1) the majority (about 70%) not containing granular vesicles, probably cholinergic elements; 2) those containing large granular vesicles of uniform size (80-110 nm), with granules of medium density and prominent halos; and 3) those containing vesicles of variable size (60-150 nm), with very dense eccentrically placed granular cores. Some non-neuronal 'granule-containing' cells were present, mainly near small blood vessels. Some 95% of the total axon profiles within the ganglia were cholinergic, the remaining 5% were adrenergic. However, 99% of synapses (i.e. axons within 50 nm of nerve cell membrane with pre- and post-synaptic specialisations) were cholinergic, and 1% were adrenergic. Only three examples of nerve cell bodies exhibiting both cholinergic and adrenergic synapses were observed. Unlike the para- and prevertebral ganglia, the pelvic ganglia contained large numbers of axo-somatic synapses. As many as 20% of the nucleated neuronal cell profiles displayed two distinct nuclei.


Cadmium toxicity on mouse pre-implantation zygotes in vitro: interactions of cadmium with manganese, zinc and calcium ions.
Simultaneous treatment with cadmium chloride (5 micrograms/ml medium) and manganese chloride (5 or 10 micrograms/ml medium) was less toxic to mouse pre-implantation zygotes in vitro than cadmium alone. Such a protective effect of manganese, resembling that of zinc, suggests that amelioration of cadmium-treated pre-embryos in vitro is not unique to zinc. The amelioration may require only the presence of another divalent metallic ion, such as zinc or manganese, which is capable of competing with cadmium for binding sites possibly involved in uptake. Under calcium-free conditions cadmium embryotoxicity is enhanced, showing a summation effect of the cadmium toxicity and the lack of calcium. This supports the notion that excessive exogenous calcium may render the effects of cadmium on compaction inconspicuous. The non-compacted pre-embryos treated with 5 micrograms/ml cadmium in a calcium-free medium had fewer blastomeres than those treated at a lower dose of 1 microgram/ml. Cadmium appeared to inhibit the cleavage from 8-cell to 16-cell stage, but not from 4-cell to 8-cell.


Integration of transcriptomic and metabolomic analyses reveal the molecular responses of the mud crab Scylla paramamosain to infection by an undescribed endoparasite Portunion sp.
Portunion is a rare endoparasitic isopod genus, recently observed inhabiting the hemocoel of the commercially important mud crab, Scylla paramamosain. For better understanding of the host-parasite interaction between S. paramamosain and Portunion sp., the metabolomic and transcriptomic changes in the hemolymph of the S. paramamosain were analyzed. We detected a total of 143 and 126 differentially accumulated metabolites in the positive and negative modes, respectively. Pathways related to amino acids and vitamin synthesis, such as Aminoacyl-tRNA biosynthesis, Tyrosine metabolism, Cysteine and methionine metabolism, Vitamin B6 metabolism, and Biotin metabolism were significantly enriched. Based on the transcriptomic data, a total of 942 differentially expressed genes were identified, of which 25 and 36 were significantly related to the immune system and metabolic pathways, respectively. Based on the metabolomic and transcriptomic data, 90 correlated metabolite-gene pairs were selected to build a regulatory network. Common significantly enriched pathways, including Starch and sucrose metabolism, Metabolism of xenobiotics by cytochrome P450, Aminoacyl-tRNA biosynthesis, Nitrogen metabolism, and Galactose metabolism were detected. On the basis of our analysis, the endoparasite Portunion sp. places a heavy metabolic burden on the host, particularly with respect to fundamental resources, such as amino acids, vitamins, carbohydrates, and lipids. In summary, these data provide an overview of the global metabolic and transcriptomic changes of the S. paramamosain resulting from Portunion sp. infection.


Incidence of childhood and adolescence epilepsy: a community-based prospective study in the province of Ferrara and in Copparo, Italy, 1996-2005.
The annual incidence of childhood and adolescence epilepsy ranges from 41 to 97 diagnoses per 100,000 people in western Countries, with a reported decline over time. We aimed at studying the incidence of epilepsy in children and adolescents (1 month to 14 years) and its temporal trend in the province of Ferrara, northern Italy. We implemented a community-based prospective multi-source registry. All children with newly diagnosed epilepsy in the period 1996-2005 were recorded. The incidence rate of newly diagnosed epilepsy in the considered age range was 57 per 100,000 person-years, (95% CI: 49.3-65.9), with a peak in the first year of life (109.4; 95% CI: 69.4-164.1), without differences between the two gender. The estimates were significantly lower than those observed previously (97.3; 95% CI: 81.9-115.7). Incidence rates for epilepsy in the Italian population aged 1 month to 14 years are in line with those of other European and Northern American Countries. The incidence of childhood epilepsy has declined over time in our area. A reduced impact of serious perinatal adverse events could partly explain the decline.


The dolichol pathway of N-linked glycosylation.
The oligosaccharide substrate for the N-linked protein glycosylation is assembled at the membrane of the endoplasmic reticulum. Dolichyl pyrophosphate serves as a carrier in this biosynthetic pathway. In this review, we discuss the function of the lipid carrier dolichol in oligosaccharide assembly and give an overview of the biosynthesis of the different sugar donors required for the building of the oligosaccharide. Yeast genetic techniques have made it possible to identify many different loci encoding specific glycosyltransferases required for the precise and ordered assembly of the dolichyl pyrophosphate-linked oligosaccharide. Based on the knowledge obtained from studying this pathway in yeast, we compare it to the process of N-linked protein glycosylation in archaea. We suggest that N-linked glycosylation in eukaryotes and in archaea share a common evolutionary origin.


Discussing care decisions at the internal medicine outpatient clinic: A conversation analysis.
Explore how often, when and how care decisions are discussed during consultations at an internal medicine outpatient clinic, and what we can learn from these observations. Qualitative analysis of 150 video-taped consultations. Consultations involving a discussion of care decisions were analyzed using conversation analysis. 1) Only 21 of the 150 consultations involved a discussion of care decisions; 2) As there is no destined phase for the introduction of the topic of care decisions, the topic is most often introduced at the end of the phase 'treatment and course of the disease'; 3) A lot of interactional effort is needed to create common ground and make relevance clear with extensive justification. Hesitation markers, repairs and hypothetical talk show the precariousness of the topic. Three dilemma's need to be addressed: 1) a slot has to be created to introduce the topic of care decisions; 2) common ground has to be created, possibly over time; 3) the paradox of framing the topic as relevant 'in the future' but 'needs to be discussed now' needs to be attended to. We recommend that physician training should address the three dilemmas. Future research should focus on how to do so.


Stabilization of total ossicular replacement prosthesis using cartilage "shoe" graft.
We aimed to determine the effect of a cartilage shoe graft placed between the foot of the TORP and the stapes footplate on hearing improvement and long-term displacement rates. Patients who underwent TORP ossiculoplasty were divided into two groups. The TORP-alone group consisted of 32 patients who underwent TORP placement without cartilage shoe graft and served as the control group. The study group consisted of 56 patients who underwent placement of cartilage shoe graft together with TORP. Pure-tone audiometry was administered to all patients before and 3, 6 and 12 months after surgery. Indications for surgery, surgical technique used, postoperative complications, and air and bone conduction thresholds at 500, 1000, 2000 and 4000 Hz were recorded for all patients. No significant difference in postoperative air-bone gaps was observed between the groups. The number of patients with air-bone gaps less than 20 dB was 14 (25%) in the study group and 8 (25%) in the control group. There was no significant difference in changes in air-bone gaps between the groups. Dislocation of the prosthesis was observed in 3 patients in the study group (5.3%) and 4 in the control group (12.5%). There was less dislocation of the prosthesis in the study group, but the difference was not statistically significant. Placement of a cartilage graft between the footplate of the stapes and the foot of the prosthesis may have positive effects on long-term hearing improvement and rates of prosthesis displacement. Further research with larger patient numbers is needed to identify the advantages of shoe graft.


Hemiplegia and the billowing mitral leaflet syndrome.
Four young patients presenting with major neurological episodes and with coexisting prolapsing mitral valve are described. An attempt at correlating the two entities is made. The neurological complications of prolapsing mitral valve are stressed.


Cytochalasin D as excitation-contraction uncoupler for optically mapping action potentials in wedges of ventricular myocardium.
Cytochalasin D in tissue bath superfusate inhibits the contraction of isolated thin trabeculae from canine right ventricle without affecting the intracellular action potential recorded with glass microelectrode. The purpose of this study was to test whether cytochalasin D could also be used to immobilize perfused wedges of ventricular muscle without affecting the action potential duration or propagation, and also to determine the optimal concentration and time duration of drug in the perfusate. Using a membrane potential sensitive dye, di-4-ANEPPS, and a high-resolution photodiode optical mapping system at a rate of 1,000 frames/sec, we recorded action potentials on the transmural surface of arterially perfused wedges of muscle from the canine left ventricular free wall. We also recorded arterial pulse pressure as a surrogate for tissue contraction. Cytochalasin D at > or = 20 micromol/L in the perfusate for > or = 6 minutes reduced the arterial pulse pressure to approximately one tenth of its initial value and significantly reduced or eliminated motion artifacts in the action potentials. A sustained concentration of 10 micromol/L cytochalasin D in the perfusate prevented contraction from recurring after the tissue was immobilized with an initial concentration of 25 micromol/L. Cytochalasin D had little effect on the action potential duration and on its transmural gradient, and did not slow the transmural velocity of excitation propagation. Cytochalasin D can be used to uncouple excitation and contraction in perfused canine cardiac muscle for the fluorescent-optical mapping of action potentials without affecting action potential duration or slowing transmural propagation.


Relationship quality, coital frequency, and condom use as predictors of incident genital Chlamydia trachomatis infection among adolescent women.
To explore associations of relationship quality, coital frequency, unprotected coitus, and chlamydia infection over time. Data came from 142 adolescent females with sexually transmitted infections attending three primary care adolescent clinics and one county STD clinic. Interview data were collected at 3 time points: enrollment, 1 month, and 3 months after enrollment. Predictor variables included relationship quality, coital frequency, unprotected coitus, and partner change. The outcome variable was infection with C. trachomatis at 3 months. Analyses were conducted using structural equation modeling. Chlamydia infection at 3 months was directly influenced by unprotected coitus during the previous 2 months (Beta = .25; p < or = .05) and partner change during the enrollment/1-month interval. Unprotected coitus was directly associated with coital frequency, both cross-sectionally and longitudinally. Increased relationship quality was associated with increased coital frequency but did not have direct effects on unprotected coitus. The data showed a protective effect of condom use for chlamydia infections. Prevention efforts should attend to the interpersonal factors behind decisions to use or not use condoms.


Laryngeal cancer survival in Zaragoza (Spain): a population-based study.
This article aims to study larynx cancer survival from the Population-Based Cancer Registry of Zaragoza, Spain, for the period 1978-2002. The survival rates were calculated using the Kaplan-Meier method. The automated calculation of the Catalan Institute of Oncology was utilised to obtain the relative survival. The observed survival rate was 84.6% in the first year and 60.9% in the fifth year. The one-year relative survival in both genders was 86.8% (CI 95%: 85.3-88.4) and 70.1% (CI 95%: 67.8-72.4) after five years. Glottic cancer presented a better survival rate than supraglottic and subglottic cancers, and a better survival rate was also observed in younger ages. There were no statistical differences when comparing survival rates by gender and between the periods 1978-1986, 1987-1994 and 1995-2002. The data suggest there were no significant changes in laryngeal cancer survival in the province of Zaragoza in the period 1978-2002 and that the tumours located in the glottis presented a better prognosis.


The effects of 1,25-dihydroxycholecalciferol on embryonic bone in vitro: a biochemical and histological study.
Explants from embryonic rat and mouse calvaria were cultivated in the presence of different concentrations of 1, 25-dihydroxycholecalciferol (1, 25-(OH)2D3). The bone resorbing effects of the vitamin D3 metabolite were evaluated by measuring the release of calcium, phosphate, lactate and citrate into the culture medium after 24 h of cultivation. The influence on bone morphology was studied using embryonic mouse radii, in which histological phenomena in the bony, cartilagenous and connective tissue compartments were observed. Both kinds of experiments show that 1, 25-(OH)2D3 has effects on embryonic bone which are typical for high concentrations of parathyroid hormone (PTH). However, the maximal effects on calcium release and on histology are 2.5 times less than those of PTH. In addition, some of the histological features such as the effects on epiphyseal cartilage and on osteoclasts were not observed. 1, 25-(OH)2D3 in concentrations up to 2 X 10(-9) M does not affect basal or PTH-stimulated cAMP levels in embryonic rat calvaria. In a concentration of 1 X 10(-8) M, however, a significant decrease in PTH-stimulated cAMP production was found. It is concluded from these in vitro experiments that (1) 1, 25-(OH)2D3 stimulates bone resorption, and (2) in 1, 25-(OH)2D3-induced bone resorption cAMP is apparently not involved as a second messenger.