Attitudes of carers and the elderly occupants of residential homes to antimicrobial chewing gum as an aid to oral health.
The aim of this study was to investigate the attitudes of elderly residents to using an antimicrobial chewing gum as an aid to oral health, and the opinion of their carers on such a procedure. A cross-sectional, multi-centre survey using a structured interview/questionnaire conducted with elderly residents and their carers. In January 1998, 9 residential/nursing homes were chosen at random from all the homes in West Hertfordshire, 207 residents were asked to chew two pieces of gum twice daily for 7 days. The participants, 148 women and 59 men, were aged between 53-100 years (mean age 82.23 +/- 9.62 years). 47 carers, all female, were involved in distributing and collecting the gum. 122 residents (58.9%) were edentulous and 85 (41%) of the participants were partially dentate. Of those with teeth 23 (27%) had 21 teeth or more. 73 (35.2%) residents found that chewing the gum was difficult with 37 (17.9%) of this group being unable to chew (P < 0.0001 for those residents with no teeth/dentures or dentures unopposed by teeth or other dentures). 32 (18.6%) subjects disliked the flavour of the gum. Of the 170 residents who chewed the gum 99 (57.2%) found it reduced oral dryness and 78 (45.1%) reported it made their mouth feel healthy. 34 (53.6%) of the dentate and 47 (40.9%) of the edentate residents wished to keep using the gum (P < 0.05). 35 (74.5%) of the carers found it easy to distribute the gum and 29 (61.7%) thought that chewing gum was an acceptable method of maintaining oral health for residents. The antimicrobial gum investigated in this study was acceptable to many elderly occupants and their carers, significantly improving perceived oral health and oral dryness of residents.


Spectroelectrochemistry of P700 in native photosystem I particles and diethyl ether-treated thylakoid membranes from spinach and Thermosynechococcus elongatus.
The redox potentials (E(composite function')) of P700 in intact and diethyl ether-treated thylakoid membranes as well as native photosystem (PS) I particles from spinach and Thermosynechococcus elongatus have been measured by a spectroelectrochemistry with an error range of +/-2-3 mV. Stepwise removal of antenna pigments by ether treatment caused distinct shifts of the E( composite function') value with increasing degree of water saturation in ether; negatively from +471 to +428 mV for spinach, but positively from +423 to +436 mV for T. elongatus. Such a contrasting behavior is discussed by invoking the mode of action of ether on the microenvironments around P700.


Role of intravascular ultrasound in endovascular management of nutcracker syndrome: A case report.
Here, we describe nutcracker syndrome management using intravascular ultrasound (IVUS) during endovascular stent placement of the renal vein. A 60-year-old woman with a known Factor V Leiden mutation, long-standing smoking history, and family history of pancreatic cancer presented with 2 years of intermittent left upper quadrant pain (LUQ) and a 15 lb unintentional weight loss. Work-up included abdominal ultrasound (US) and abdominal computerized tomography (CT) scan. Abdominal US and Chest CT scan were negative while the abdominal CT scan revealed severe compression of the left renal vein by the superior mesenteric artery, consistent with nutcracker syndrome. Renal venogram and endovascular stent placement performed under IVUS guidance. IVUS was used to determine stent size and measure flow and assess patency after stent placement. Post-renal vein stent placement, the patient had resolution of her symptoms with follow-up duplex renal ultrasound exam demonstrating restored blood flow in the left renal vein with improved patency.


Cost-effective one-spot hydrothermal synthesis of graphene oxide nanoparticles for wastewater remediation: AI-enhanced approach for transition metal oxides.
Outer ear infections (OEs) affect millions of people each year and are associated with significant medical costs.The usage of multiple antibiotics to treat ear contamination is a concern because it can have an environmental impact, especially on soil and water.The increased use of antibiotics has exposed bacterial ecosystems to high concentrations of antibiotic residues.Although there have been efforts to minimize the impact of antibiotics, adsorption methods have yielded better and more viable results, and carbon-based materials are effective for environmental remediation.Graphene oxide (GO) is a versatile material used in various applications such as nanocomposites, antibacterial agents, photocatalysis, electronics, and biomedicine.GO can act as an antibiotic carrier and affect the antibacterial efficacy of antibiotics.However, the processes responsible for the antibacterial activity of GO and antibiotics in treating ear infections are unknown.This study investigates the effect of GO on the antibacterial activity of tetracycline (TT) against Escherichia coli (E.coli)-negative bacteria.Artificial Neural Network-Genetic Algorithm (ANN-GA) was applied to analyze data on the effectiveness of different doses and combinations of graphene oxide and antibiotics in treating ear infections.This study could help identify the most effective treatment protocols and potentially reduce the risk of antibiotic resistance.The R-squared (R2) value, RMSE, and MSE all fall within the proper levels for fitting criteria, with R2 ≥ 0.97 (97%), RMSE ≤ 0.036064, and MSE ≤ 0.00199 (6% variance).The outcomes showed high antimicrobial activity, resulting in a 5-log decline of E.coli.In experiments, GO was shown to coat the bacteria, interfere with their cell membranes, and aid in the prevention of bacterial growth, although this effect was somewhat weaker for E.coli.The concentration and duration at which bare GO can kill E.coli are both important factors.The antibacterial activity of antibiotics can be either boosted or reduced by the presence of GO, depending on the GO's interaction with the antibiotic, the GO's contact with the microbe, and the sensitivity of the bacteria to the antibiotic.The antibacterial efficiency of the combination of GO and antibiotics varies depending on the specific antibiotic and microorganism being targeted.


Worry, rumination and negative metacognitive beliefs as moderators of outcomes of Transdiagnostic group cognitive-behavioural therapy in emotional disorders.
Despite the relevance of cognitive processes such as rumination, worry, negative metacognitive beliefs in emotional disorders, the existing literature about how these cognitive processes moderate the effect of treatment in treatment outcomes is limited. The aim of the present study was to explore the potential moderator effect of baseline cognitive processes-worry, rumination and negative metacognitive beliefs-on the relationship between treatment allocation (transdiagnostic cognitive-behavioural therapy -TD-CBT plus treatment as usual-TAU vs. TAU alone) and treatment outcomes (anxiety and depressive symptoms, quality of life [QoL], and functioning) in primary care patients with emotional disorders. A total of 631 participants completed scales to evaluate worry, rumination, negative metacognitive beliefs, QoL, functioning, and anxiety and depressive symptoms. Worry and rumination acted as moderators on the effect of treatment for anxiety (b = -1.25, p = .003; b = -0.98, p = .048 respectively) and depressive symptoms (b = -1.21, p = .017; b = -1.34, p = .024 respectively). Individuals with higher baseline levels of worry and rumination obtained a greater reduction in emotional symptoms from the addition TD-CBT to TAU. Negative metacognitive beliefs were not a significant moderator of any treatment outcome. The study assesses cognitive processes over a relatively short period of time and uses self-reported instruments. In addition, it only includes individuals with mild or moderate anxiety or depressive disorders, which limits generalization to other populations. These results underscore the generalization of the TD-CBT to individuals with emotional disorders in primary care with different cognitive profiles, especially those with high levels of worry and rumination.


Longitudinal trajectories of depression and anxiety among adolescents during COVID-19 lockdown in China.
This study examines the patterns and predictors of depression and anxiety trajectories among adolescents during COVID-19 lockdown in China. A total of 35,516 college students were followed from the pandemic outbreak period, initial remission period, and control period. Participants completed the Patient Heath Questionnaire, Generalized Anxiety Disorder Scale, Perceived Social Support Scale, the Simplified Coping Style Questionnaire, and APGAR-family scale. Distinct patterns of depression and anxiety trajectories were established through grouping participants based on time-varying changes of the cut-off score. Multivariate logistic regressions were used to examine predictors for trajectory membership. Depression and anxiety prevalence during the COVID-19 outbreak were 21.3% and 11.5% respectively, and symptoms worsened as the lockdown time increased. Five depression/anxiety trajectories were observed: resistance, recovery, relapsing/remitting, delayed-dysfunction and chronic-dysfunction. Gender, academic year, residence location, history of mental health, and COVID-19 community exposure were significant predictors of distinct trajectories for depression or anxiety. Less social support or positive coping, more negative coping, and poorer family function were also risk predictors for not developing delayed or chronic dysfunction. Although most adolescents remain euthymic or recover over time, some adolescents, especially those with the risk factors noted above, exhibit delayed or chronic symptoms. Thus, the need for individualized intervention with these adolescents is indicated.


Polytetrafluoroethylene for interim restoration of post spaces.
Bacterial recontamination of the empty space is of concern in the time between the post space preparation and cementation of a cast post-and-core. This dental technique describes a novel treatment approach with sterilized polytetrafluoroethylene tape and a reinforced zinc-oxide eugenol restorative material to maintaining asepsis of the root canal space while awaiting fabrication and delivery of a cast post-and-core. On delivery of the cast post-and-core, the material can be removed with minimal time and effort.


Hemostasis in Airway Surgery: Adult and Pediatric.
Surgical bleeding is an unlikely, but potentially devastating, event during the surgical management of pediatric and adult laryngotracheal disorders. Therefore, an intimate knowledge of the anatomy of the large vessels coursing in the vicinity of the airway is imperative. Anatomic variants in the position of the inominate artery or the superior thyroid artery can place individuals with these variations at particular risk in these cases. Delayed bleeding from an inominate artery fistula is a particularly devastating complication from open airway surgery. A high index of suspicion is necessary to allow for early identification and aggressive treatment of this potential complication.


[Investigations on the performance of calcium selective disc-electrodes with electrically charged and neutral ligands in anaerobic serum measurements (author's transl)].
Anaerobically prepared serum samples from healthy subjects were simultaneously analysed for Ca++ in a flow-through-system of three ion selective disc-electrodes (electrochemical multimeasurementsystem). Two of the sensors contained electrically charged ligands, the third contained a neutral carrier. With neutral carriers an improvement of performance was noted in that there was a large increase in selectivity toward H+- and NH+4-ions and a distinct enhancement of reproducibility.


N-(4-Meth-oxy-2-nitro-phen-yl)acetamide.
In the title compound, C9H10N2O4, the three substituents vary in the degree of lack of planarity with the central phenyl ring. The meth-oxy group is nearest to being coplanar, with a C-C-O-C torsion angle of 6.1 (5)°. The nitro group is less coplanar, with a 12.8 (5)° twist about the C-N bond and the acetamido group is considerably less coplanar with the central ring, having a 25.4 (5)° twist about the C-N bond to the ring. The NH group forms an intra-molecular N-H⋯O hydrogen bond to a nitro-group O atom.


Frequency and Characteristics of First-Time Palliative Care Referrals During the Last Day of Life.
Palliative care referrals (PCRs) improve symptom management, provide psychosocial and spiritual support, clarify goals of care, and facilitate discharge planning. However, very late PCR can result in increased clinician distress and prevent patients and families from benefiting from the full spectrum of interdisciplinary care. To determine the frequency and predictors of PCR within 24 hours of death. Consecutive first-time inpatient PCR from September 1, 2013 to August 31, 2017 was identified to determine the frequency and predictors of referrals within 24 hours of death. We compared the clinical characteristics with a random sample of patients discharged alive or died more than 24 hours after first-time PCR as a control, stratified by year of consult in a 1:1 ratio. Of 7322 first-time PCRs, 154 (2%) died within 24 hours of referral. These patients were older (P = 0.003) and had higher scores for depression (P = 0.0009), drowsiness (P = 0.02), and shortness of breath (P = 0.008) compared with a random sample of 153 patients discharged alive or died more than 24 hours after first-time PCR. Patients who received a PCR within 24 hours of death were more likely than the control group to have Eastern Cooperative Oncology Group 4 (95% vs. 25%, P < 0.0001), delirium (89% vs. 17%, P < 0.0001), do-not-resuscitate code status (81% vs. 18%, P < 0.0001), and hematologic malignancies (39% vs. 16%, P < 0.0001). In the multivariate analysis, depression (odds ratio [OR] 1.4; P = 0.005), do-not-resuscitate code status (OR 9.1; P = 0.003), and Eastern Cooperative Oncology Group 4 (OR 9.8; P = 0.003) were independently associated with first-time PCR within 24 hours of death. Although only a small proportion of first-time PCR occurred in the last 24 hours of life, the patients had a significant amount of distress, indicating a missed opportunity for timely palliative care intervention. These sentinel events call for specific guidelines to better support patients, families, and clinicians during this difficult time. Further research is needed to understand how to minimize very late PCR.


Electrophoretic heterogeneity of 5-phosphoribosyl-1-pyrophosphate synthetase within and among humans.
The product of the enzyme 5-phosphoribosyl-1-pyrophosphate (PPriboseP) synthetase is a substrate for purine, pyrimidine, and pyridine biosynthesis and may be rate limiting for purine biosynthesis. A system developed to electrophoretically separate and histochemically detect PPriboseP synthetase in crude cell extracts has facilitated the identification of electrophoretically variant enzyme forms in the erythrocytes of five patients from a patient population of 200. Additional studies of human organs obtained at autopsy revealed a unique electrophoretic mobility for nearly each organ within the same individual.


The two transcription units of the autonomous parvovirus minute virus of mice are transcribed in a temporal order.
Using quantitative RNase protection assays, we have monitored the appearance of mRNAs generated during lytic infection of tightly synchronized murine cells by the autonomous parvovirus minute virus of mice. Our results demonstrate that transcripts from the P4 promoter can be detected prior to those from the P39 promoter, providing direct evidence for a temporal order of expression between the two parvovirus promoters.


Ontology-Based and Architecture-Based Method for the Development of Interoperable Care Systems for Type 2 Diabetes Mellitus.
Processes like the care of type 2 diabetes mellitus patients require support by information systems considering the heterogeneity of the actors from different domains involved, enabling harmonization and integration of their specific methodologies and knowledge representation approaches towards interdisciplinary cooperation. Currently, the development of systems starts from the simplified information world, ignoring the aforementioned heterogeneity and specificity of real-world processes. This paper aims to demonstrate the feasibility of developing an adaptive, interoperable and intelligent system that supports the major aspects of type 2 diabetes mellitus care based on the Generic Component Model as formal methodology for modelling universal systems. The result is a deployable solution based on a formal representation of the diabetes care system, its objectives, and the intended business process. The implemented system enables reasoning over the data, inferring medical diagnosis. The effectiveness of the inference was evaluated, obtaining an F-measure of 0.89. The methods presented in this paper helps to build high quality models based on computation-independent aspects, which enable the construction of knowledge-based adaptive, intelligent and interoperable eHealth systems.


Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis.
Evaluation of costs and short-term cost-effectiveness of infliximab plus methotrexate (IFX + MTX); triple therapy of hydroxychloquine, sulphasalazine, and methotrexate (TRIPLE); or methotrexate monotherapy (MTX) in patients with new-onset polyarticular juvenile idiopathic arthritis (JIA). In a prospective multicenter study (ACUTE-JIA), costs and health outcomes of 60 randomized patients with new-onset disease-modifying anti-rheumatic drug (DMARD)-naïve polyarticular JIA were analyzed during the first year. A mapping algorithm was used to obtain utility values from Child Health Assessment Questionnaire (CHAQ). Wallace criteriae were used to assess clinically inactive disease (CID). Linear regression with non-parametric bootstrapping was used to adjust imbalances at baseline. Using prices for IFX biosimilar, adjusted annual mean (SD) costs of treatment (€) were 21,164 (4158), 12,136 (5286), and 18,300 (8635) on IFX + MTX, TRIPLE, and MTX, respectively. Incremental cost-effectiveness ratio (ICER) for IFX + MTX as compared with TRIPLE or MTX were 3442 € or 678 € per additional month spent in CID. Mean (SD) quality-adjusted life years (QALYs) for IFX + MTX, TRIPLE and MTX were 0.755 (0.065), 0.725 (0.062), and 0.686 (0.124). ICER for IFX + MTX vs TRIPLE was 294,433 €, and for IFX + MTX vs MTX 31,435 € per QALY gained. In short-term, biosimilar IFX + MTX can be considered cost-effective when compared with MTX alone. TRIPLE was cost-effective when compared with MTX and showed cost advantage when compared with IFX + MTX. Cost per time spent in CID showed similar results than ICER evaluations. This trial was primarily registered with the Ethical Board of Helsinki District University Hospital ( https://www.hus.fi ), clinical trial number 211864, and later with ClinicalTrials.gov, number NCT01015547.


A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase.
Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.


Covered metallic stents with an anti-migration design vs. uncovered stents for the palliation of malignant gastric outlet obstruction: a multicenter, randomized trial.
Previous studies reported comparable stent patency between covered self-expandable metallic stents (SEMS) and uncovered SEMS (UCS) for palliation of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the efficacy and safety of the newly developed WAVE-covered SEMS (WCS), which has an anti-migration design, compared with UCS in gastric cancer patients with symptomatic GOO. A total of 102 inoperable gastric cancer patients with symptomatic GOO were prospectively enrolled from five referral centers and randomized to undergo UCS or WCS placement. Stent patency and recurrence of obstructive symptoms were assessed at 8 weeks and 16 weeks after stent placement. At the 8-week follow-up, both stent patency rates (72.5% vs. 62.7%) and re-intervention rates (19.6% vs. 19.6%) were comparable between the WCS and the UCS groups. Both stent stenosis (2.4% vs. 8.1%) and migration rates (9.5% vs. 5.4%) were comparable between WCS and UCS groups. At the 16-week follow-up, however, the WCS group had a significantly higher stent patency rate than the UCS group (68.6% vs. 41.2%). Re-intervention rates in the WCS and UCS groups were 23.5% and 39.2%, respectively. Compared with the UCS group, the WCS group had a significantly lower stent restenosis rate (7.1% vs. 37.8%) and a comparable migration rate (9.5% vs. 5.4%). Overall stent patency was significantly longer in the WCS group than in the UCS group. No stent-associated significant adverse events occurred in either the WCS or UCS groups. In the multivariate analysis, WCS placement and chemotherapy were identified as independent predictors of 16-week stent patency. WCS group showed comparable migration rate and significantly more durable long-term stent patency compared with UCS group for the palliation of GOO in patients with inoperable gastric cancer.


Do negative affect characteristics and subjective memory concerns increase risk for late life anxiety?
To better understand the development and exacerbation of late-life anxiety, we tested a risk model positing that trait negative affect (NA) characteristics would interact with cognitive functioning, thereby increasing some older adults' risk for increased anxiety symptoms. The moderator-mediator model consisted of measures of NA, cognitive functioning, and their interaction, as predictors of later Hamilton Anxiety Rating Scale scores (HARS) via a mediational process, subjective memory concerns (SMCs). Older adults (aged 65-years and over; M(age)=76.7 years, SD=6.90 years) completed evaluations four times over approximately 18 months. A latent growth curve model including Anxiety Sensitivity Index total score (ASI), Mattis Dementia Rating Scale-2 (DRS) total raw score, the ASI×DRS interaction, a SMC measure as mediator, HARS intercept (scores at times 3 and 4), and HARS slope provided good fit. The ASI×DRS-2 interaction at Time 1 predicted HARS slope score (β=-.34, p<.05). When ASI score was high, stronger cognitive functioning was associated with fewer anxiety symptoms. The indirect effect of ASI score predicting HARS score 18-months later through the SMC mediator was statistically significant (β=.08, p<.05). Results suggest that the cognitive functioning changes associated with aging might contribute to the development of anxiety symptoms in older adults with specific NA traits. Implications for predicting and preventing late life anxiety disorders are discussed.


In vitro kinetic analysis of the role of the positive charge at the amino-terminal region of signal peptides in translocation of secretory protein across the cytoplasmic membrane in Escherichia coli.
By using an in vitro system for the translocation of secretory proteins in Escherichia coli, detailed and quantitative studies were performed as to the function of the positively charged amino acid residues at the amino terminus of the signal peptide. Uncleavable OmpF-Lpp, a model secretory protein carrying an uncleavable signal peptide, and mutant proteins derived from it were used as translocation substrates. When the positive charge, +2 (LysArg) for the wild-type, was changed to 0, -1, or -2, little or no translocation was observed. The number of the positive charge was altered by introducing different numbers of Lys or Arg residues into the amino terminus. The rate of translocation was roughly proportional to this number, irrespective of whether the charged amino acid residues were Lys or Arg. When the amino-terminal LysArg was replaced by His residues, translocation took place more efficiently at pH 6.5 than pH 8.0, whereas that of the wild-type was about the same as the two pH values. We conclude that the signal peptide requires a positive charge at its amino-terminal region to function in the translocation reaction and that the rate of translocation is roughly proportional to the number of the positively charged group, irrespective of the amino acid species that donates the charge. Evidence suggesting that the positive charge is involved in the binding of precursor proteins to the membrane surface to initiate translocation is also presented.


Myositis ossificans and fibroosseous pseudotumor of digits: a clinicopathological review of 64 cases with emphasis on diagnostic pitfalls.
Myositis ossificans (MO) and fibroosseous pseudotumor of digits (FP) are pseudotumoral mimics of malignancy. A review of 50 cases of MO and 14 cases of FP showed that a malignant diagnosis was suggested by referring pathologists in 23% of MO and 9% of FP. The most common misdiagnosis was osteosarcoma. Awareness of the spectrum of clinicopathological features of MO and FP will help pathologists avoid misdiagnoses. A comparison of the clinicopathological features of MO and FP showed that most features were similar, but FP involved an older age group (p<0.001). MO showed a statistically significant higher tendency to contain fibrinous material (p=0.007), edematous lymphangioma-like areas (p=0.013), and cartilage (p=0.017) and FP to contain excessive immature osteoid (p=0.029). These differences may be related to the site of occurrence.


HNF1α upregulation and promoter hypermethylation as a cause of glucose dysregulation: a case-control study of Kashmiri MODY population.
HNF1α transcription factor regulates a network of genes involved in the development of β-cells and also serves as a model for transcription defects in pancreatic β-cells; mutations in this gene cause MODY. The goal of this study was to assess the promoter methylation and expression profile of the most common MODY causing gene, HNF1α, in Kashmiri MODY patients, as factors responsible for glucose dysregulation, as no such study had been performed on MODY patients in Kashmir previously. The study included 85 Kashmiri subjects. Samples were extracted for DNA and RNA using standard protocols. The HNF1α promoter methylation profile was assessed by bisulfite conversion of the DNA followed by MSP, whereas qPCR was used for expression analysis. The expression of HNF1α was found to be upregulated (p value 0.0349*) in majority of MODY (60%) and T1D (72%) cases (p value 0.0349*). HNF1α expression was 1.33-fold higher in MODY cases with hypermethylated HNF1α promoters (p value 0.0360*). HNF1α expression was upregulated by 2.3-fold in MODY patients with HbA1c levels > 7% (p value 0.0025**). MODY cases with FBS levels > 7.7 mmol/l were upregulated by 0.646-fold than those with FBS levels ≤ 7.7 mmol/l (p value 0.0161*). In this study, we found that as glucose dysregulation progresses, blood FBS, RBS, and HbA1c levels rise, and that at higher levels, HNF1α expression rises as well. From the results obtained, we may conclude that HNF1α is strongly upregulated in MODY, thus indicating the deleterious effect of over expression of HNF1α gene on glucose regulation.


Forskolin and the release of noradrenaline in cerebrocortical slices.
The role of adenosine 3',5'-cyclic monophosphate (cAMP) in the release of noradrenaline from central neurones has been investigated by examining the effects of forskolin, 3-isobutyl-l-methylxanthine (IBMX), cis-6-(p-acetamidophenyl)-1,2,3,4,4a, 10b-hexahydro-8,9-dimethoxy-2-methyl-benzo[c] [1,6]-naphthyridine bis (+ +hydrogenmaleinate) (AH21-132; a new phosphodiesterase inhibitor) and N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphate (dibutyryl-cAMP) on the outflow of tritiated compounds from rat and rabbit cerebral cortex slices preincubated with [3H]-noradrenaline. Forskolin, IBMX, AH21-132 and dibutyryl-cAMP produced a concentration-dependent increase in both basal and electrically-evoked efflux of tritium from rat and rabbit cortex slices. The increase in basal tritium efflux from rabbit cortex slices elicited by forskolin and IBMX could be attributed mainly to an increase in [3H]-DOPEG although a small increase in [3H]-noradrenaline was also observed. Forskolin and (when combined with noradrenaline) IBMX and AH21-132 increased the cAMP content of rat cortex slices at similar or somewhat higher concentrations that they increased tritium efflux. Neither forskolin nor IBMX or AH21-132 had any effect on the cocaine-sensitive uptake of [3H]-noradrenaline into synaptosomes prepared from rat or rabbit cortex. The effects of forskolin, IBMX and dibutyryl-cAMP on electrically-evoked overflow of tritium from rat and rabbit cortex slices were reduced when cocaine (10 microM) was present in the superfusion medium, although forskolin produced a similar increase in cAMP in the absence or presence of cocaine. It is suggested that cAMP may facilitate the normal process of noradrenaline release by nerve stimulation.


Computers in anesthesia and intensive care: lack of evidence that the central unit serves as reservoir of pathogens.
Computers are becoming increasingly visible in operating rooms (OR) and intensive care units (ICU) for use in bedside documentation. Recently, they have been suspected as possibly acting as reservoirs for microorganisms and vehicles for the transfer of pathogens to patients, causing nosocomial infections. The purpose of this study was to examine the microbiological (bacteriological and mycological) contamination of the central unit of computers used in an OR, a surgical and a pediatric ICU of a tertiary teaching hospital. Sterile swab samples were taken from five sites in each of 13 computers stationed at the two ICUs and 12 computers at the OR. Sample sites within the chassis housing of the computer processing unit (CPU) included the CPU fan, ventilator, and metal casing. External sites were the ventilator and the bottom of the computer tower. Quantitative and qualitative microbiological analyses were performed according to commonly used methods. One hundred and ninety sites were cultured for bacteria and fungi. Analyses of swabs taken at five equivalent sites inside and outside the computer chassis did not find any significant-number of potentially pathogenic bacteria or fungi. This can probably be attributed to either the absence or the low number of pathogens detected on the surfaces. Microbial contamination in the CPU of OR and ICU computers is too low for designating them as a reservoir for microorganisms.


Predicting outcome of malignant external otitis.
Malignant external otitis (MEO) continues to pose a diagnostic and therapeutic challenge. The lack of a diagnostic study since 1987 combined with recent findings of quinolone-resistant MEO prompted the present analysis of MEO outcome in a major tertiary medical center. Seventy-five consecutive patients hospitalized for suspected MEO between 1990 and 2003 were divided into 2 diagnostic groups: MEO Type 1, presence of all obligatory clinical and radiologic criteria and most of the occasional criteria of Cohen and Friedman or absence of 1 obligatory criterion with failure of intensive treatment, and MEO Type 2, absence of one of the obligatory criteria with treatment response within 1 week. The groups were compared for demographic data, underlying diseases, ear parameters, culture findings, length of hospitalization, and treatment before hospitalization, obtained from the charts. Both types of MEO affected mostly diabetic patients and were characterized by granulations and discharge in the external ear, severe prolonged pain, soft tissue involvement and bone destruction on computed tomographic scan, and growth of Pseudomonas aeruginosa in culture. However, Type 1 MEO was associated with a significantly older patient age at presentation, higher rate of oral antidiabetic treatment, history of diabetic (vascular) complications, computed tomographic findings of nasopharyngeal involvement (soft tissue swelling, soft tissue asymmetry, or abscess formation), bone destruction, and temporomandibular joint involvement-all of which led to significantly longer treatment and shorter survival. The worse prognosis of Type 1 MEO compared with Type 2 should alert clinicians to establish earlier diagnosis and treatment.


High and dysregulated secretion of epidermal growth factor from immune cells of patients with relapsing-remitting multiple sclerosis.
We studied the secretion and regulation of epidermal growth factor (EGF) from immune cells of patients with relapsing remitting multiple sclerosis (RR-MS), and the relevance of these levels to neuronal morphology and survival. Our data suggest that the immune-mediated neuronal and oligodendroglial regeneration may be defective by the increased EGF secretion from immune cells of RR-MS patients. We also suggest an increased neurotoxicity of the immune response in RR-MS via high levels of EGF secretion. This is a heretofore unreported aspect of the immune response of patients with RR-MS. Our results may support the inadequate tissue repair that has been observed in MS.


Local and Systemic Therapy of Recurrent Medulloblastomas in Children and Adolescents: Results of the P-HIT-REZ 2005 Study.
Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9-16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7-10.0) and 18.5 months (CI: 13.6-23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival.


The Coronary Artery Surgery Study (CASS). A critical appraisal.
The applicability of the Coronary Artery Surgery Study (CASS) to clinical practice is seriously hampered by the following findings. (1) The CASS randomized study applies to only a small minority of patients with coronary artery disease. Attempts to extend the conclusions of CASS to the vast majority of patients with coronary artery disease are unjustified. (2) The high percentage of crossover of the medical group made it impossible for CASS to accomplish its primary goal of contrasting medical and surgical treatment. (3) Despite the fact that crossover of medically assigned patients created a bias against surgical treatment, the observed mortality in the surgical group was still 31% lower than that in the medical group. (4) The failure of CASS to find this difference to be statistically significant must take into account the fact that the statistical power of CASS was so low that a real difference was likely to be overlooked. (5) The conclusion that patients similar to those in the study may safely defer operation is unwarranted and violates the principles of prospective study design. In addition, CASS failed to address the possibility that deferring operation may compromise long-term survival.


Endoscopic Endonasal Optic Nerve Decompression in Idiopathic Intracranial Hypertension: When to Implement Optic Nerve Sheath Fenestration.
Idiopathic intracranial hypertension (IIH) is a syndrome characterized with increased intracranial pressure and normal cerebrospinal fluid (CSF) composition. Treatment is mainly conservative, whereas CSF diversion surgery is the most frequently used surgical intervention. Endoscopic endonasal optic nerve decompression (EOND) is a newer surgical treatment of this patient group. This study presents a single clinic's case series with comparative results of unilateral an bilateral EOND with or without optic nerve fenestration. Sixteen patients with IIH syndrome who underwent 18 EOND procedures by a single neurosurgeon were evaluated with MRI and digitally subtracted angiography preoperatively. Both preoperative and postoperative visual acuity and perimetry and fundoscopy examinations were routinely performed. All patients underwent sphenoidotomy using the endoscopic binostril approach; however, unilateral or bilateral optic nerve decompression and accompanying optic sheath fenestration was determined on a case-by-case basis, after which all patients were also evaluated for the outcome of headaches. Most of the patients were female, and the mean age was 30.28 ± 9.78 years. CSF pressure was increased in all patients (406.43 ± 112.91 mm of H 2 O), and the follow-up period was 61.72 ± 21.67 months. In patients with unilateral EOND, visual fields improved in 83%, visual acuity in 70%, headache in 75%, and papilledema in 27% of cases. In patients with bilateral EOND, perimetry improved in 86%, visual acuity in 43%, headache in 50%, and papilledema in 57% of cases. EOND is an effective surgical option in the treatment of IIH. Bilateral decompression is preferable in patients with bilateral visual involvement, and optic nerve fenestration may prove to be helpful in patients with IIH whose primary complaint is headache.


Cross-reactions of anti-DNA autoantibodies with cell surface proteins.
Anti-DNA autoantibodies are thought to play a major role in the pathogenesis of systemic lupus erythematosus. However, the mechanism(s) by which they participate in tissue and organ damage is not well understood. It has been suggested that these antibodies combine with DNA or DNA-histone complexes to produce circulating immune complexes which may deposit in various tissues. Alternatively, anti-DNA autoantibodies could interact directly with tissue components by way of immunological cross-reaction. In this study we have used a panel of mouse monoclonal autoantibodies with anti-nuclear specificity and measured their binding to membrane proteins of several tissues and cell lines. We show that the anti-DNA antibodies, but not anti-RNA or anti-histone antibodies bind to membrane proteins of molecular weights 102, 80, 42, 35 and 31 kDa, which are expressed in different combinations on several cell types. The binding of anti-DNA antibodies to these cell surface proteins was not affected by DNase treatment of the target cells, was increased by DNase treatment of the antibody preparations and was completely inhibited by DNA, indicating a true cross-reaction and not an indirect interaction of antibody and membrane proteins through a DNA bridge. Our results suggest that direct binding of anti-DNA autoantibodies to cell surface membrane proteins may play an important role in the induction of the pleomorphic tissue damage in systemic lupus erythematosus.


Effect of drug dose and timing of treatment on the emergence of drug resistance in vivo in a malaria model.
There is a significant interest in identifying clinically effective drug treatment regimens that minimize the de novo evolution of antimicrobial resistance in pathogen populations. However, in vivo studies that vary treatment regimens and directly measure drug resistance evolution are rare. Here, we experimentally investigate the role of drug dose and treatment timing on resistance evolution in an animal model. In a series of experiments, we measured the emergence of atovaquone-resistant mutants of Plasmodium chabaudi in laboratory mice, as a function of dose or timing of treatment (day post-infection) with the antimalarial drug atovaquone. The likelihood of high-level resistance emergence increased with atovaquone dose. When varying the timing of treatment, treating either very early or late in infection reduced the risk of resistance. When we varied starting inoculum, resistance was more likely at intermediate inoculum sizes, which correlated with the largest population sizes at time of treatment. (i) Higher doses do not always minimize resistance emergence and can promote the emergence of high-level resistance. (ii) Altering treatment timing affects the risk of resistance emergence, likely due to the size of the population at the time of treatment, although we did not test the effect of immunity whose influence may have been important in the case of late treatment. (iii) Finding the 'right' dose and 'right' time to maximize clinical gains and limit resistance emergence can vary depending on biological context and was non-trivial even in our simplified experiments. In a mouse model of malaria, higher drug doses led to increases in drug resistance. The timing of drug treatment also impacted resistance emergence, likely due to the size of the population at the time of treatment.


Spin-engineering magnetic media.
The explosion in demand for increased data-storage density is driving the exploration of new magnetic media. Here we describe a new type of magnetic medium in which the spin configurations are engineered in chemically homogeneous magnetic films: regularly arranged in-plane and out-of-plane spin configurations are defined by altering the magnetic anisotropy. These spin-engineered media not only maintain the surface planarity but also the homogeneity of the magnetic materials, and our method is likely to find immediate application on account of its simplicity and ease of integration.


Gadd45 beta forms a homodimeric complex that binds tightly to MKK7.
Gadd45 alpha, beta, and gamma proteins, also known as growth arrest and DNA damage-inducible factors, have a number of cellular functions, including cell-cycle regulation and propagation of signals produced by a variety of cellular stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45 beta has been indicated as a major player in the endogenous NF-kappaB-mediated resistance to apoptosis in a variety of cell lines. In fibroblasts this mechanism involves the inactivation of MKK7, the upstream activator of JNK, by direct binding within the kinase ATP pocket. On the basis of a number of experimental data, the structures of Gadd45 beta and the Gadd45 beta-MKK7 complex have been predicted recently and data show that interactions are mediated by acidic loops 1 and 2, and helices 3 and 4 of Gadd45 beta. Here, we provide further evidence that Gadd45 beta is a prevailingly alpha-helical protein and that in solution it is able to form non covalent dimers but not higher-order oligomers, in contrast to what has been reported for the homologous Gadd45 alpha. We show that the contact region between the two monomers is comprised of the predicted helix 1 (residues Q17-Q33) and helix 5 (residues K131-R146) of the protein, which appear to be antiparallel and to form a large dimerisation surface not involved in MKK7 recognition. The results suggest the occurrence of a large complex containing at least an MKK7-Gadd45 beta:Gadd45 beta-MKK7 tetrameric unit whose complexity could be further increased by the dimeric nature of the isolated MKK7.


[Measurement of pupillary diameter in diabetic and non-diabetic patients: a case-control study].
To study the effect of type 2 diabetes on pupil diameter. We carried out a case-control study at the Douala Obstetrics, Gynecology and Pediatric Hospital over a 5-month period. The cases were type 2 diabetic patients, and the controls were non-diabetic patients paired for age and gender. We studied the correlation between the duration of diabetes, fasting blood sugar and the horizontal pupil diameter. We included 35 patients in each group. The mean age was 56.6±10.01 years. Both groups included 17 males and 18 females. The mean duration of diabetes was 2.72±4.31 years, and the mean fasting blood sugar was 2.02±0.69g/L. The mean pupil diameter was similar in the two groups. On the right side, it was 4.75±0.73mm for controls and 4.52±0.69mm for cases (P=0.179). On the left side, it was 4.70±0.68mm and 4.42±0.73mm respectively for each group (P=0.101). The duration of diabetes was correlated to pupil diameter in the right eye (r=-0.43; P=0.01) and left eye (r=-0.45; P<0.01). No additional risk was found to be associated with diabetes for right pupil diameters (OR=0.79; P=0.33), or for left ones (OR=0.76; P=0.24). Pupil diameter is similar in diabetic and non-diabetic patients. However, the duration of diabetes appears to affect pupil diameter.


Absence of a directly causative role for human herpesvirus 7 in human lymphoma and a review of human herpesvirus 6 in human malignancy.
In search of a (new) viral etiological agent, we screened 64 lymph node samples from Hodgkin's disease (HD) and 43 samples (32 lymph node and 11 skin biopsies) from non-Hodgkin's lymphoma (NHL) for human herpesvirus 7 (HHV-7). Twenty-nine control samples were tested as well, including 17 with benign lymphadenopathy. None of the samples tested positive by Southern blot hybridization using HHV-7-specific probes. We conclude that there is no major HHV-7 load in human lymphoma and that HHV-7 is not likely to be directly involved in its etiology. This is in contrast to a small minority of human lymphoproliferative diseases in which HHV-6 can be found at high copy number, but in which an etiological role is still uncertain.


Quantitative Intracerebral Hemorrhage Localization.
The location of intracerebral hemorrhage (ICH) is currently described in a qualitative way; we provide a quantitative framework for estimating ICH engagement and its relevance to stroke outcomes. We analyzed 111 patients with ICH from the Minimally Invasive Surgery Plus Recombinant-Tissue Plasminogen Activator for Intracerebral Evacuation (MISTIE) II clinical trial. We estimated ICH engagement at a population level using image registration of computed tomographic scans to a template and a previously labeled atlas. Predictive regions of National Institutes of Health Stroke Scale and Glasgow Coma Scale stroke severity scores, collected at enrollment, were estimated. The percent coverage of the ICH by these regions strongly outperformed the reader-labeled locations. The adjusted R(2) almost doubled from 0.129 (reader-labeled model) to 0.254 (quantitative location model) for National Institutes of Health Stroke Scale and more than tripled from 0.069 (reader-labeled model) to 0.214 (quantitative location model). A permutation test confirmed that the new predictive regions are more predictive than chance: P<0.001 for National Institutes of Health Stroke Scale and P<0.01 for Glasgow Coma Scale. Objective measures of ICH location and engagement using advanced computed tomographic imaging processing provide finer, objective, and more quantitative anatomic information than that provided by human readers. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00224770.


Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials.
The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.


Detection of autoantibodies to recombinant human thyroid peroxidase by sensitive enzyme immunoassay.
Autoantibodies to thyroid peroxidase (TPO), the thyroid 'microsomal' antigen, are widely utilized in the diagnosis of human autoimmune thyroid disease. Crude human thyroid preparations of TPO are of differing potency, contain residual thyroglobulin (Tg) and other human membrane antigens, and are available in only limited amounts. Hence, immunoassays for anti-TPO are unstandardized and of variable sensitivity and specificity. We co-transfected the Chinese hamster ovary (CHO) cell line with a full-length human TPO cDNA expression plasmid. We selected a high expressing recombinant TPO positive cell population (CHO-TPO) by Northern blot analysis, then fluorescence laser flow cytometry using both human polyclonal and murine monoclonal anti-TPO antibodies. Solubilized 100,000 g membrane preparations from both CHO-TPO and CHO cells were used as antigens in a specific ELISA with CHO antigen serving as background control. In a selected series of known anti-TPO positive (n = 46) and negative (n = 73) sera there was a high correlation between ELISAs utilizing recombinant or natural-TPO antigen (r = 0.93). There appeared to be no difference in the affinity of high titre human anti-TPO for recombinant and natural-TPO antigen with both ELISAs able to detect 0.05 U/ml of anti-TPO activity (reference preparation NIBSC 66/387). These data predict a new era in standardized thyroid autoantibody testing utilizing recombinant antigen preparations.


Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population-based study in Italy.
To assess rates and determinants of treatment discontinuation of or changes in initial antihypertensive drug therapy in a large cohort of patients from Lombardia (Italy). The cohort included 445356 patients aged 40 -80 years who received their first antihypertensive drug prescription (monotherapy) during 1999--2002. Discontinuation was defined by the absence of any antihypertensive prescription during a 90-day period following the end of the latest prescription. If during the same period a drug of a different class was added or replaced the initial prescription, treatment modification was regarded as combination or switching, respectively. Competing risks methodology was used to estimate and compare cause-specific cumulative incidence. Cumulative incidences of discontinuation, combination and switching were respectively 33, 14 and 15% at 6 months, 41, 18 and 17% at 1 year, and 50, 25 and 19% at 5 years since initial treatment. Compared with patients starting treatment with angiotensin-converting enzyme inhibitors, the rate of discontinuation was less for patients on angiotensin receptor blockers with a hazard ratio of 0.92 (95% confidence interval =0.90-0.94), whereas increased discontinuation was observed for patients starting with other drugs, mainly beta-blockers with a hazard ratio of 1.64 (1.62-1.67); and diuretics with a hazard ratio of 1.83 (1.81-1.85). In the general population of Lombardia, discontinuation of the initial single antihypertensive drug treatment is a common phenomenon, whereas switching to another monotherapy and to combination treatment occur at similarly much lower rates. Blockers of the renin-angiotensin system are associated with the lowest incidence of treatment discontinuation.


In-depth mapping carboxylic acid metabolome reveals the potential biomarkers in colorectal cancer through characteristic fragment ions and metabolic flux.
Carboxylic acid metabolome plays vital roles in the study of pathological mechanisms about cancer. This study aimed to find potential biomarkers for colorectal cancer (CRC) using carboxylic acids profiling. However, the identification of much more carboxylic acids was limited due to poor ionization efficiency and lack of characteristic fragment ions. Derivatization-liquid chromatography-mass spectrometry, which contains characteristic MS/MS fragments ions, were performed for carboxylic acid metabolomics analysis in CRC serum samples. 1054 carboxylic acids were quickly and selectively identified after extraction using three characteristic fragment ions and elucidation using the most suitable CE at 30 eV. Among them, 605 carboxylic acids exhibit discriminating levels between healthy and CRC patients in training cohort. Furthermore, the differential metabolites were found to be mainly enriched in amino acid metabolism, fatty acid biosynthesis and TCA cycle by MetaboAnalyst and iPath analysis. Finally, serine, glycine, and methionine were determined as the potential biomarkers after further confirmation using validation cohort and in vitro metabolic flux analysis. The above results collectively demonstrated that a new set of carboxylic acids can be quickly and selectively discovered using characteristic fragment ions.


What does absence of lymph node in resected specimen mean after neoadjuvant chemoradiation for rectal cancer.
The effect of insufficient node sampling in patients with rectal cancer managed by neoadjuvant chemoradiation followed by surgery has not been clearly determined. We evalulated the impact of insufficient sampling or even abscence of lymph nodes in the specimen on survival in patients at high-risk (T3, T4 or node positive) for rectal cancer. We conducted a single institution, retrospective analysis of all patients who underwent surgical rectal resection following neoadjuvant chemoradiation for treatment of mid to lower rectal cancer between 1997 and 2009. ypNX was defined as the absence of lymph nodes retrieved in the resected specimen. A total of 132 patients underwent resection for treatment of rectal cancer following neoadjuvant chemoradiation. Ninety four patients (71.2%) were considered as having node-negative disease, including ypNx and ypN0. In 38 patients (28.8%), the primary tumor was associated with regional lymph node metastases (ypNpos). The mean number of retrieved nodes per specimen was 14.2, respectively. The five-year overall survival from initial operation for the ypNx group was 100%, respectively. The estimated five-year overall survival for ypN0 and ypNpos was 84.0% and 60.3%, respectively (P =0.001). No significant differences in overall survival were observed between the ypNx and ypN0 group (P =0.302). Absence of recovered LN in resected specimens after neoadjuvant chemoradiation was observed in 7.6% of specimens. Absence of LN should not be regarded as a risk factor for poor survival or as a sign of less radical surgery.


Rebampide enema therapy as a treatment for patients with chronic radiation proctitis: initial treatment or when other methods of conservative management have failed.
Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. There have been no formal trials of treatment for radiation proctitis and a variety of methods are currently used. We assessed the efficacy of rebamipide enema to control symptoms and proctoscopic findings from radiation proctitis. Fifteen patients with radiation proctitis were enrolled. Enemas containing 150 mg rebamipide per dosing were administered after morning bowel movement, and always prior to bedtime, twice daily for 4 weeks. The efficacy of treatment was assessed from clinical symptoms (Subjective Objective Management Analysis Scale for Rectal Toxicity) and endoscopic findings. The mean bleeding score improved from 2.67 to 0.53 (P < 0.01). The mean symptom scores improved in those patients who had pain (0.40 to 0.13), tenesmus (0.40 to 0.20), and stool frequency (0.27 to 0.13). The mean improvement in telangiectasia scores (2.13 to 0.80, P < 0.01), bleeding point scores (1.80 to 0.27, P < 0.01), and friable mucosa scores (1.33 to 0.20, P < 0.01) were all statistically significant. No side effects were noted in any patients. Rebamipide enema therapy for radiation proctitis is a safe and effective treatment of radiation proctitis. We suggest the value of rebamipide enema in the treatment of radiation proctitis when other conservative management or first treatment has failed.


Simulation of coupling between chemical reactions and ion transport in brown adipose tissue using network thermodynamics.
Several cellular events associated with energy turnover in the mitochondria and at the Na+/K+ plasma membrane pump have been formulated in terms of network thermodynamics. The calorigenic role of the Na+/K+ pump is examined in terms of the relationship between the movement of sodium and potassium ions and the chemical reactions involved. In addition, attention is centered on the potential thermogenic role of three mitochondrial pathways involving proton fluxes--namely, one in which protons are transported from the matrix to the intermembrane space; a second in which protons are transferred back into the matrix in conjunction with the synthesis of ATP; and a third wherein protons re-enter the matrix without being coupled to any chemical reaction. (This latter pathway has been delineated by studies on isolated mitochondria and may be unique to brown fat.) At both sites (plasma membrane and mitochondria) the conversion of chemical energy to heat is considered.


p53 mutation pattern and expression of c-erbB2 and c-met in gastric cancer: relation to histological subtypes, Helicobacter pylori infection, and prognosis.
The molecular mechanisms of Helicobacter pylori associated tumor development are poorly understood. The spectra of genetic alterations in neoplasms may provide clues to the molecular carcinogenesis of a tumor and may be relevant for the prognosis of the patients. We investigated the p53 mutation pattern and the protein expression of p53, c-erbB2, and c-met in 42 gastric cancers and correlated these alterations with H. pylori infection, histological subtypes and survival of the patients after curative resection. There were no differences in the incidences of the expression of p53, c-erbB2, and c-met in the tumor tissues according to H. pylori infection. Fifteen p53 mutations in 12 (29%) tumors were identified. More p53 mutations were found in patients with positive serology for H. pylori (43% vs 14%). This difference was not significant, but the small sample size may be insufficient to detect a potential statistical difference. There was neither a H. pylori-associated p53 hot-spot codon mutation nor a H. pylori characteristic mutational pattern of p53. Positive lymph nodes (P = 0.0061) and p53 mutations (P = 0.0035) were the only significant bad prognostic markers for survival after curative resection of the gastric cancers in our study. Our study does not indicate a unique molecular mechanism of p53 mutagenesis through H. pylori infection. The fact that p53 mutations were significantly correlated with poor survival of patients after potentially curative resection of gastric cancer may have clinical implications for multimodal therapies.


A Study on New IAP 2015 Growth References in Rural South Indian Children.
To ascertain the utility of the new pan Indian 2015 IAP references in rural South Indian children and the ability of new IAP charts to recognise children with abnormal cardiometabolic risk factors in 10 to 16 y age group. Among school health camps conducted at two centres of Tamil Nadu- rural Vellore and rural Erode- height, weight, waist circumference, blood pressure, triceps skin-fold thickness and body fat percentage were measured by trained pediatricians and Z-scores calculated. The anthropometric measures were studied as per IAP 2015 references and compared to other national and international references. Their utility in identification of malnutrition and cardiometabolic risk ascertained. A total of 420 children (210 from Erode and 210 from Vellore) in the age group of 10 to 16 y were included in the study. New IAP references recognized more short stature (4.2 vs. 3%), wasting (11 vs. 1.5%) and overweight (14.2 vs. 13.2%) children compared to old IAP charts. The Z-scores of anthropometric measures as per New IAP 2015 references had significant correlation with old IAP and other international data (p < 0.05). It was noted that new IAP charts could detect 83.3%, old IAP chart 50% and WHO 83.3% of subjects with malnutrition. New IAP charts could detect 70.3% cardiometabolic risk associated with over nutrition compared to old IAP (57.4%) and WHO (51.8%). There is a significant prevalence of both under nutrition and overweight in rural setting. IAP 2015 reference is useful to diagnose children with under nutrition and overweight including abnormal cardiometabolic risk.


Diarrhea associated with Cyanobacterialike bodies in an immunocompetent host. An unusual epidemiological source.
To describe a patient who developed diarrhea secondary to Cyanobacterialike bodies (CLBs) after exposure to contaminated water in his home. Case report. General community. Healthy, elderly man. None, self-limited illness. The patient's clinical course was consistent with illness caused by CLBs. Cyanobacterialike bodies were recovered from the patient's stool sample and the contaminated water to which he was exposed. Internists and laboratory technicians should be aware of CLBs as a cause of protracted diarrhea in the community.


Low-dose and same day use of polyethylene glycol improves image of video capsule endoscopy: A multi-center randomized clinical trial.
Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene glycol (PEG) for small bowel preparation before VCE. A total of 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into five groups: Group A (no PEG), Group B (1-L PEG, 12 h before VCE), Group C (2-L PEG, 12 h before VCE), Group D (1-L PEG, 4 h before VCE), and Group E (2-L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D, and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs 10.8%, P = 0.0035). Patient acceptance of 1-L PEG was better than of 2-L PEG (P < 0.005). Small bowel cleansing with 1-L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance (ClinicalTrials.gov, ID: NCT02486536).


Methionine synthase activities in mice following acute exposures to ethanol and nitrous oxide.
Acute or chronic exposure to nitrous oxide or chronic exposure to ethanol decreases the activity of the vitamin B12-dependent enzyme methionine synthase. To assess the combined effect of acute exposure to nitrous oxide and ethanol, mice were given an intraperitoneal injection of ethanol (3 g/kg) and exposed to an inspired mixture of 66% nitrous oxide and 34% oxygen for 4 hr. Methionine synthase activities in liver, kidney, and brain were measured immediately after exposure to nitrous oxide and at various times over a 4-day recovery period. Methionine synthase activities in liver and kidney returned to control levels 2-4 days following inactivation. In brain, a significant 16% decrease in methionine synthase activity remained after a 4-day recovery period. The acute administration of ethanol did not alter the magnitude of the inactivation induced by nitrous oxide nor the time course of recovery of methionine synthase activity following inactivation. Moreover, in mice that were not exposed to nitrous oxide, methionine synthase activity was not altered by the acute administration of ethanol alone or in combination with 0.4% atm isoflurane. Thus, in this animal model, an acute dose of ethanol does not alter methionine synthase activity nor does it enhance the inactivation produced by nitrous oxide.


Ultraviolet-light-evoked phase shifts in the locomotor activity rhythm of the field mouse Mus booduga.
The circadian rhythm of locomotor activity in the nocturnal field mouse Mus booduga has been monitored after an exposure to ultraviolet-A (UV-A; wavelength between 350 and 400 nm) radiation at various hours of the subject's cycle. The magnitude of the phase shift is used to determine the sensitivity of the circadian pacemaker underlying locomotor activity rhythm. It is observed that UV-A shifts the phase of the locomotor activity rhythm in a phase-dependent manner. A phase response curve (PRC) is constructed to depict the time course and waveform of the basic oscillator's sensitivity to UV-A radiation. The UV-A PRC qualitatively resembles the PRC constructed using diffused daylight as stimulus. Furthermore, the phase response characteristics of the circadian pacemaker for UV-A suggest a periodically varying sensitivity to UV-A similar to that to daylight.


Role of zinc and zinc transporters in the molecular pathogenesis of diabetes mellitus.
Diabetes is one of the most common chronic diseases in the United States. An estimated 18.2 million people in the US (6.3%) have diabetes; among them 2.8 million are African Americans (AAs). On average, AAs are twice as likely to have diabetes as European Americans (EAs) of similar age. AAs disproportionately suffer from various diseases in the US. Many of these diseases include hypertension, cardiovascular disease (CVD), diabetes mellitus (DM-beta predominantly Type II), and cancers of the prostate and pancreas. A number of risk factors such as smoking, a high fat diet, little physical activity, stress, and meager access to health care have been the subject of numerous investigations. However, the factor of the interaction between genetics and the environment has received very little attention in the scientific community. Of note, the content of zinc in pancreatic beta gells is among the highest in the body; however, very little is known about the uptake and storage of zinc inside these cells. We hypothesize that one of the major reason AAs disproportionally suffer from DM (as well as some other illnesses like prostate cancer, CVD and hypertension) is due to their inherent inability to transport appropriate amount of zinc in the crucial cell types that require relatively higher amount of zinc than the other cell types. In this article, we will explore in detail the possible genetic and environmental link between human zinc transporters (hZIPs) and their differential expressions in the islet beta cells from AAs as compared to other racial groups, particularly EAs, in both normal healthy individuals and diabetic patients. We hypothesize that the hZIPs play an important role in the development of diabetes, and the main reason AAs disproportionately suffer from DM (as well as other illnesses like prostate and pancreatic cancers, hypertension, and CVD) as compared to EAs may be due the low degree of expressions of the critical zinc transporters in the beta cells. Understanding the molecular events in the pathogenesis of DM with regards to regulation of zinc uptake would be critical to the evaluation of the natural history of diabetes in humans and especially in various racial groups. If a direct link between zinc transport and diabetes can be established, then a special nutritional formula, medication or other intervention might be especially designed to test the ability to decrease the incidence of this disease in DM susceptible groups, particularly in AAs.


Anatomical variants identified on chest computed tomography of 1000+ COVID-19 patients from an open-access dataset.
Chest computed tomography (CT) has been the preferred imaging modality during the pandemic owing to its sensitivity in detecting COVID-19 infections. Recently, a large number of COVID-19 imaging datasets have been deposited in public databases, leading to rapid advances in COVID-19 research. However, the application of these datasets beyond COVID-19-related research has been little explored. The authors believe that they could be used in anatomical research to elucidate the link between anatomy and disease and to study disease-related alterations to normal anatomy. Therefore, the present study was designed to investigate the prevalence of six well-known anatomical variants in the thorax using open-access CT images obtained from over 1000 Iranian COVID-19 patients aged between 6 and 89 years (60.9% male and 39.1% female). In brief, we found that the azygos lobe, tracheal bronchus, and cardiac bronchus were present in 0.8%, 0.2%, and 0% of the patients, respectively. Variations of the sternum, including sternal foramen, episternal ossicles, and sternalis muscle, were observed in 9.6%, 2.9%, and 1.5%, respectively. We believe anatomists could benefit from using open-access datasets as raw materials for research because these datasets are freely accessible and are abundant, though further research is needed to evaluate the uses of other datasets from different body regions and imaging modalities. Radiologists should also be aware of these common anatomical variants when examining lung CTs, especially since the use of this imaging modality has increased during the pandemic.


Comparison of signal detection of tumour necrosis factor-α inhibitors using the Korea Adverse Events Reporting System Database, 2005-2016.
There are no pharmacovigilance studies on adverse event (AE) data for tumour necrosis factor alpha (TNFα) inhibitors in South Korea. We analysed AEs induced by adalimumab, infliximab, and etanercept METHODS: We used data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Events Reporting System Database (KIDS-KD) collected between 2005 and 2016. We used three different signal detection methods: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The drug was compared with drug labels in the USA and Korea. Logistic regression analysis identified AEs that are more likely to occur with drug use. Of the 5594 AEs identified, 350, 452, and 71 were related to adalimumab, infliximab, and etanercept, respectively. We identified seven new signals, which were not listed on drug labels in either Korea or the USA, for AEs associated with the study drugs: two for adalimumab (medication error and drug failure), two for infliximab (palpitation and temperature sensation change), and three for etanercept (hyperkeratosis, acne, and thyroid neoplasm malignant). Injection site pain (OR 6.14, 95% CI 1.15-32.74) and alopecia (OR 4.54, 95% CI 1.16-17.77) for adalimumab, chest pain (OR 6.01, 95% CI 1.35-26.77) for infliximab, and uveitis (OR 10.11, 95% CI 1.13-90.77) for etanercept were more likely to be reported in patients with each TNFα inhibitor than in those without, respectively. Seven new signals that were not included in the current label were identified for TNFα inhibitors and should be updated and monitored.Key Points• Large-scale spontaneous AE reporting data and data mining techniques are useful for detecting signals of rare AEs as well as common AEs induced by drugs.• Drug labels should be updated to reflect signals that are newly discovered by continuous monitoring.


Highly selective separation of enantiomers using a chiral porous organic cage.
Porous solids composed of shape-persistent organic cage molecules have attracted considerable attention due to their important applications such as molecular separation, heterogeneous catalysis, and gas storage. In this study, an imine-linked porous organic cage (POC) CC10 diluted with a polysiloxane OV-1701 was explored as a novel stationary phase for high-resolution gas chromatography (GC). A wide variety of enantiomers belonging to different classes of organic compounds have been resolved on the coated capillary column, including chiral alcohols, esters, ketones, ethers, halohydrocarbons, epoxides, and organic acids. The fabricated column complements to commercial β-DEX 120 column and our recently reported CC3-R column for separating enantiomers, which indicates that the excellent chiral recognition ability of CC10 is not only interesting academically, but also has potential for practical application. In addition, CC10 also exhibits good selectivity for the separation of n-alkanes, n-alcohols, Grob mixture, and positional isomers. This work also indicates that this type of chiral POCs will become a new class of chiral selector in the near future.


Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis.
METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.


A Novel Spherical Crystallization Method Using Pickering Emulsions.
Spherical crystallization is a promising process intensification technique, where surfactant is an important ingredient in formulation but needs to be used carefully due to toxicological reasons. This work proposes to adopt colloidal particles stabilized Pickering emulsions for spherical crystallization, in order to eliminate or reduce the surfactant use. A representative system is selected for study, where silica nanoparticles are prepared to stabilize emulsions and evaporative crystallization of ibuprofen is carried out. Depletion attraction is exploited to improve the Pickering emulsion stability for better confining on crystallization with two depletants PEG and PVA tested. Crystal products from the emulsions prepared with silica nanoparticles and the non-ionic surfactant Tween 20 are compared. The results show that depletion attraction is helpful for producing stable Pickering emulsions with high dispersed phase fraction and mono-dispersed ibuprofen spherical agglomerates. Silica nanoparticles contribute to reduced induction time by boosting heterogeneous nucleation and mitigate secondary agglomeration possibly by steric effects.


A new total distal radioulnar joint prosthesis: functional outcome.
To present the evolution of design and the short-term functional outcome of our distal radioulnar joint (DRUJ) prosthesis. This total DRUJ prosthesis differs from others in that it consists of 2 parts and attains bony fixation by its hydroxyapatite coating. Nineteen patients received a DRUJ prosthesis after a failed Darrach procedure (n = 10), Sauvé-Kapandji procedure (n = 7), trauma (n = 1), or DRUJ synovitis (n = 1). Indications for the placement were decreased grip, decreased forearm motion, and pain due to ulnar impingement syndrome and instability of the distal ulna. Seven prostheses were removed, 5 due to loosening, 1 due to continuing pain, and 1 at the request of the patient. The 5 prostheses that loosened were an intermediate prototype no longer in use. In 12 remaining cases, range of motion, grip strength, and pinch strength were measured, and patients completed the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Pain was assessed with the visual analog scale (range, 0-10). A paired t-test was performed to assess the significance of the difference between preoperative and postoperative measurements. Statistically significant improvements were seen in forearm pronation, from an average of 79° to 88°; grip strength, from an average of 10 kg to an average of 16 kg; and visual analog scale score, decreased from a mean of 5.3 to a mean of 3.5. The distal ulna was clinically stable in all 12 patients who retained the prosthesis. The intermediate prototype had a high failure rate, 5 out of 5. The early results for the current prosthesis prototype show clinical improvement. Based on these results, we conclude that this prosthesis offers a new treatment option for ulnar instability after distal ulnar resection. Therapeutic IV.


Two apparent glucose-6-phosphate dehydrogenase variants in normal XY males: G6PD Alabama.
A six-year-old black boy who had transient hemolysis after a viral infection was found to have mildly decreased red cell glucose-6-phosphate dehydrogenase (G6PD) activity (1.25 IU/g hemoglobin). Two G6PD bands, both slightly faster than normal G6PD B, were seen on electrophoresis in both the propositus as well as in his maternal grandfather. This is an unexpected finding, since the G6PD gene is located on the long arm of the X chromosome that is subject to X-chromosome inactivation, and available evidence indicates that it is present as a single functional copy in the human genome. The obvious possibility of duplication of the X chromosome was eliminated by cytogenetic analysis with G-banding. G6PD duplication is unlikely, since peripheral blood granulocytes, platelets, and lymphocytes; cultured skin and bone marrow fibroblasts; and Epstein-Barr virus-stimulated lymphocytes yielded only a single electrophoretic band with mobility identical to the slower band seen in crude red blood cell hemolysate. Study of partially purified red blood cell hemolysate G6PD also yielded a single band with identical mobility. Kinetic studies of the enzyme in the propositus and in three generations of his family identified a unique, previously unpublished G6PD mutant that is herein designated G6PD Alabama. Red blood cells were separated by density gradient into a reticulocyte-enriched, an intermediate, and a dense, older portion. Two distinct enzyme bands were identified on electrophoresis of hemolysate from the reticulocyte-enriched portion, but not from the other two portions. It is postulated that two transcriptional products of the mutant G6PD gene exist; one with a short half-life and detectable only in young red blood cells, and another with a longer half-life present in all cells. The existence of two distinct mutant genes in the genome or a unique post-translational form of the mutant G6PD detected only in reticulocytes cannot be excluded.


Epidemiology of chronic inflammatory demyelinating polyradiculoneuropathy in The Netherlands.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare but disabling disorder that often requires long-term immunomodulatory treatment. Background incidence rates and prevalence and risk factors for developing CIDP are still poorly defined. In the current study, we used a longitudinal population-based cohort study in The Netherlands to assess these rates and demographic factors and comorbidity associated with CIDP. We determined the incidence rate and prevalence of CIDP between 2008 and 2017 and the occurrence of potential risk factors in a retrospective Dutch cohort study using the Integrated Primary Care Information (IPCI) database. Cases were defined as CIDP if the diagnosis of CIDP was described in the electronic medical file. In a source population of 928 030 persons with a contributing follow-up of 3 525 686 person-years, we identified 65 patients diagnosed with CIDP. The overall incidence rate was 0.68 per 100 000 person-years (95% CI 0.45-0.99). The overall prevalence was 7.00 per 100 000 individuals (95% CI 5.41-8.93). The overall incidence rate was higher in men compared to woman (IRR 3.00, 95% CI 1.27-7.11), and higher in elderly of 50 years or older compared with people <50 years of age (IRR 17 95% CI 4-73). Twenty percent of CIDP cases had DM and 9% a co-existing other auto-immune disease. These background rates are important to monitor changes in the frequency of CIDP following infectious disease outbreaks, identify potential risk factors, and to estimate the social and economic burden of CIDP.


Impaired nuclear translocation of glucocorticoid receptors: novel findings from psoriatic epidermal keratinocytes.
Psoriasis is a chronic proliferative skin disease and is usually treated with topical glucocorticoids, which act through the glucocorticoid receptor (GR), a component of the physiological systems essential for immune responses, differentiation, and homeostasis. To investigate the possible role of GR in the pathogenesis of psoriasis, normal and psoriatic lesional skin were recruited. Firstly, the immunolocalization of GR in the skin and cultured epidermal keratinocytes were determined by immunofluorescence. In normal skin and cultured human epidermal keratinocytes, intracellular GR is localized in the nuclei, while in psoriatic skin and cultured keratinocytes, GR is in the cytoplasm. Next, we investigated possible factors associated with the cytoplasmic distribution. We found that VEGF and IFN-γ led to impaired nuclear translocation of GR through p53 and microtubule-inhibitor, vincristine, and inhibited nuclear uptake of GR in normal keratinocytes. In addition to dexamethasone, interleukin (IL)-13 was also able to transfer GR into nuclei of psoriatic keratinocytes. Furthermore, discontinuation of dexamethasone induced cytoplasmic retention of GR in normal keratinocytes. In contrast, energy depletion of normal epidermal keratinocytes did not change the nuclear distribution of GR. To confirm our findings in vivo, an imiquimod-induced psoriasis-like skin mouse model was included. IL-13 ameliorated (but vincristine exacerbated) the skin lesions on the mouse. Taken together, our findings define that impaired nuclear translocation of GR is associated with VEGF, IFN-γ, p53, and microtubule. Therapeutic strategies designed to accumulate GR in the nucleus, such as IL-13, may be beneficial for the therapy of psoriasis.


Microarray methods in Drosophila neurobiology.
In the relatively short period since their development, DNA microarrays have been used increasingly in the study of genetic and cellular processes, thereby offering a genome-wide approach to gene expression studies. With the advent of genome sequencing programs for organisms from yeast to man, the number of organisms which now have ready-made commercial arrays continues to increase. Here, the principle of DNA microarrays is introduced, with particular attention being given to the role of this technology in studies of the nervous system of the fruitfly Drosophila melanogaster. The importance of experimental design and sample preparation, in line with minimum information about microarray experiment (MIAME) compliance, is emphasised. The technical platforms available to the Drosophila neurobiologist have been illustrated and a brief number of data analysis tools that are readily available reviewed.


Clinical features and natural course of pediatric longitudinal melanonychia: A retrospective cohort study in Korea.
Large studies on the clinical features and natural course of pediatric longitudinal melanonychia (LM) are lacking. To investigate the clinical features and natural course of pediatric LM. Retrospective cohort analysis of pediatric patients (age ≤ 18 years) with LM. We examined 703 LM lesions in 381 children. Single, narrow, and homogeneously pigmented fingernail lesions were most frequently observed. Our results suggested that within 3, 4.5, and 9.5 years after onset, approximately 3%, 5%, and 10% of LM lesions, respectively, will completely regress and that single, left-sided, and homogeneously pigmented lesions are more likely to disappear completely. The age of onset, sex, finger/toe position, Hutchinson's sign, and nail dystrophy were not associated with complete regression. During follow-up, most cases demonstrated no change in color or width between the first and last visit, and early darkening/widening before stabilization or lightening/narrowing was common. The lightning of pigmentation was associated with complete regression, whereas change in width was not. Retrospective study at a tertiary center. Our results suggest that clinicians ought to follow pediatric patients with LM without intervention for several years even if lesions grow darker or wider. Single, left-sided, and homogeneously colored lesions are more likely to regress.


Inhibition of RhoA Activity Does Not Rescue Synaptic Development Abnormalities and Long-Term Cognitive Impairment After Sevoflurane Exposure.
General anesthetics interfere with dendritic development and synaptogenesis, resulting in cognitive impairment in the developing animals. RhoA signal pathway plays important roles in dendritic development by regulating cytoskeleton protein such as tubulin and actin. However, it's not clear whether RhoA pathway is involved in inhaled general anesthetics sevoflurane-induced synaptic development abnormalities and long-term cognitive dysfunction. Rats at postnatal day 7 (PND7) were injected intraperitoneally with RhoA pathway inhibitor Y27632 or saline 20 min before exposed to 2.8% sevoflurane for 4 h. The apoptosis-related proteins and RhoA/CRMP2 pathway proteins in the hippocampus were measured 6 h after sevoflurane exposure. Cognitive functions were evaluated by the open field test on PND25 rats and contextual fear conditioning test on PND32-33 rats. The dendritic morphology and density of dendritic spines in the pyramidal neurons of hippocampus were determined by Golgi staining and the synaptic plasticity-related proteins were also measured on PND33 rats. Long term potentiation (LTP) from hippocampal slices was recorded on PND34-37 rats. Sevoflurane induced caspase-3 activation, decreased the ratio of Bcl-2/Bax and increased TUNEL-positive neurons in hippocampus of PND7 rats, which were attenuated by inhibition of RhoA. However, sevoflurane had no significant effects on activity of RhoA/CRMP2 pathway. Sevoflurane disturbed dendritic morphogenesis, reduced the number of dendritic spines, decreased proteins expression of PSD-95, drebrin and synaptophysin, inhibited LTP in hippocampal slices and impaired memory ability in the adolescent rats, while inhibition of RhoA activity did not rescue the changes above induced by sevoflurane. RhoA signal pathway did not participate in sevoflurane-induced dendritic and synaptic development abnormalities and cognitive dysfunction in developing rats.


Extended lymphadenectomy (D2) in patients with early gastric cancer.
To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.


Novel insights into the calcium action in cherry fruit development revealed by high-throughput mapping.
This work provides the first system-wide datasets concerning metabolic changes in calcium-treated fruits, which reveal that exogenously applied calcium may specifically reprogram sweet cherry development and ripening physiognomy. Calcium modulates a wide range of plant developmental processes; however, the regulation of fruit ripening by calcium remains largely uncharacterized. In this study, transcriptome, proteome and metabolome profiling was used to document the responses of sweet cherry fruit to external calcium application (0.5% CaCl2) at 15, 27 and 37 days after full blossom. Endogenous calcium loading in fruit across development following external calcium feeding was accompanied by a reduction in respiration rate. Calcium treatment strongly impaired water-induced fruit cracking tested by two different assays, and this effect depended on the fruit size, water temperature and light/dark conditions. Substantial changes in the levels of numerous polar/non-polar primary and secondary metabolites, including malic acid, glucose, cysteine, epicatechin and neochlorogenic acid were noticed in fruits exposed to calcium. At the onset of ripening, we identified various calcium-affected genes, including those involved in ubiquitin and cysteine signaling, that had not been associated previously with calcium function in fruit biology. Calcium specifically increased the abundance of a significant number of proteins that classified as oxidoreductases, transferases, hydrolases, lyases, and ligases. The overview of temporal changes in gene expression and corresponding protein abundance provided by interlinked analysis revealed that oxidative phosphorylation, hypersensitive response, DNA repair, stomata closure, biosynthesis of secondary metabolites, and proton-pump activity were mainly affected by calcium. This report provides the fullest characterization of expression patterns in calcium-responsive genes, proteins and metabolites currently available in fruit ripening and will serve as a blueprint for future biological endeavors.


Erythema ab igne: a case report and review of the literature.
Erythema ab igne (EAI) is a rare condition since the advent of central heating. Its incidence has been rising as heating sources are being used to treat chronic pain. Multiple activities that chronically expose patients to heating sources also have been documented with this condition. We present a case of EAI induced by the use of an electric blanket.


Oxidative degradation of pentachlorophenol by permanganate for ISCO application.
Potassium permanganate (KMnO4) has been an effective technology for the in situ chemical oxidation (ISCO) of many organic compounds including chlorinated alkanes and alkenes, but it has rarely been applied for oxidizing aromatic organochlorines. This study confirms the ability of permanganate to oxidize an aromatic chlorinated compound, pentachlorophenol (PCP), in an efficient manner at neutral pH. The rate of the reaction between KMnO4 and PCP was calculated and the results indicated that the reaction between PCP and permanganate is relatively fast with a second-order rate constant k″ ∼ 30 M-1 s-1. Besides the kinetic aspect, the authors identified the main reaction by-products, and proposed a possible reaction mechanism scheme. The general pathway shows the formation of chlorinated intermediates, and ultimately, the complete mineralization to chloride, water, and CO2 confirmed by total organic carbon and chloride measurement in solution. Flow-through column experiments, consisting of flushing a PCP-contaminated sandy or natural soil with oxidant, showed the good ability of permanganate to eliminate the pollutant. After 24 h of treatment, 77% and 56% of PCP abatement were obtained for sandy and natural soil, respectively. These findings show the high potential of permanganate for the in situ remediation of aromatic organochlorine contaminated soils.


Hemangiopericytomas in male pelvis.
All cases of hemangiopericytomas involving the male pelvis which have been reported in the English literature with clinical data have been reviewed. Their clinical features, roentgenographic findings, pathologic features, and treatment are presented with an illustrative case. The tumor is an aggressive neoplasm which characteristically produces late local recurrences or metastases. Since the clinical behavior cannot be reliably predicted from its histologic appearance, all must be regarded as malignant. Primary treatment should be en bloc excision since a high recurrence rate results when simple enucleation or excision is performed. Long-term follow-up is mandatory, and local recurrences or metastases should be resected whenever feasible. Radiation and chemotherapy may convert a nonresectable lesion into a resectable one and provide significant palliation.


Low psychosocial resources during early pregnancy are not associated with prolonged labour.
To examine if a low level of psychosocial resources in early pregnancy is associated with the occurrence of prolonged labour. A cross sectional study of 644 women expecting their first child. Participants were asked to complete a questionnaire at their first antenatal visit, measuring psychosocial resources defined as social network and support, work-related psychosocial factors, control of daily life and health characteristics. Outcome was prolonged labour at the end of the pregnancy. A low level of psychosocial resources was not associated with prolonged labour. The majority of women reported that the degree of support was high in early pregnancy. A perceived low level of psychosocial resources in early pregnancy did not increase the risk of prolonged labour at the subsequent delivery.


Assessment of regional myocardial perfusion with myocardial contrast echocardiography in a canine model of varying degrees of coronary stenosis.
Previous studies showed that myocardial contrast echocardiography can be used to detect relative regional underperfusion in a canine model of critical coronary stenoses. The aim of this study was to determine if myocardial contrast echocardiography performed with a sterile sonicated human serum albumin preparation (Albunex, Molecular Biosystems, San Diego, Calif.) could detect the presence of coronary stenoses of variable degrees of severity. The results were compared with myocardial blood flow as assessed by radiolabeled microspheres in 16 open-chest dogs during baseline, following the creation of a coronary stenosis of variable severity and at the peak of dipyridamole-induced hyperemia. When flow ratios (that is, flow in the control area/ischemic area) were examined, a good correlation was observed between the area under the time-intensity curve and radioactive microsphere blood flow (r = 0.94, p < 0.0001), which allowed distinction of mild from severe stenosis. However, a consistent underestimation of the dipyridamole-induced hyperemia by myocardial contrast echo was seen in the control zone. This could be partially explained by a simultaneous increase in coronary blood flow and blood volume with dipyridamole and by attenuation of the ultrasound signal because of the high concentration of microbubbles at high flows. Myocardial contrast echocardiography can quantitate the amount of jeopardized myocardium during various degrees of coronary stenoses.