The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass.
Noninvasive in vivo detection of gaseous microemboli in the middle cerebral artery, by transcranial Doppler ultrasound, was used to determine the effect of filtration in the arterial catheter using 25- and 40-microns filters and bubble oxygenators in patients undergoing cardiopulmonary bypass surgery. Eighteen patients undergoing coronary artery bypass surgery were studied using a closed cardiac (unvented heart) model. Group 1 patients (no filters) had the highest incidence of gaseous microemboli, as indicated by the ultrasound microemboli index, at both high and low oxygen flow rates. Group 2 patients (40-microns filters) had a significantly lower microemboli index, particularly at low oxygen flow rates (t = 4.9, p less than 0.001). The 25-microns group patients had the lowest values of all. No microemboli were detected at low oxygen flow rates, and microemboli were detected in only 0.1% of the samples at high oxygen flow rates. Additionally, observations on vented hearts in 3 patients undergoing cardiac valve surgery indicate that the origin of gaseous microemboli may be air trapped inside the heart.


One-Year Experience with the Institution of a Critical Airway Team at an Academic Medical Center.
At our institution, there were a number of adverse patient events related to an unstable airway that led to the formation of a designated critical airway response team (CAT). It was hoped that this would improve patient outcomes in such matters. Our aim was to evaluate the impact of the creation of the CAT. A review of the activations of the CAT for 1 year was conducted. We reviewed 51 CAT activations, the majority (71%) occurred in the emergency department (ED) and the most common reasons for activation were angioedema (41%) and epiglottitis (12%). Fiber optic intubation was the most common method used to secure the airway, 22% of the cases were transported to the operating room for management. Only one surgical airway was required and no adverse outcome related to the airway occurred in the studied group. The creation of a critical airway has been considered a success in terms of patient management at our institution. It has been most commonly used in the management of life-threatening angioedema in the ED.


No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis.
To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene. Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants. Patients and controls from clinical and epidemiologic collections in the United States and Europe. A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taql site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white. Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups. We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia. No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.


Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study.
According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4). Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. Retrospectively registered.


High levels of protein carboxyl methyltransferase in well-differentiated human endometrial carcinoma.
The levels of protein carboxyl methyltransferase, an enzyme that methylates free carboxyl groups of proteins, were determined in normal human proliferative and secretory endometrium and in poorly and well-differentiated endometrial carcinoma. Protein carboxyl methyltransferase activity was 67% higher in the well-differentiated carcinoma than in the normal tissues, while similar enzyme levels were observed in the two normal tissues and in the poorly differentiated carcinoma. The results suggest that in the well-differentiated tumor there is excessive protein methylation and offer a possible biochemical probe for distinguishing between the two types of tumor.


Influence of the endothelium on the amplification by serotonin of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rabbit isolated ear artery.
The influence of the vascular endothelium on the amplifying effect of serotonin on steady-state responses to noradrenaline (NA) and sympathetic nerve stimulation (SNS) has been studied in the rabbit isolated ear artery. Removal of the endothelium abolished the dilator effect of acetylcholine (ACh, 1 microM) obtained in the presence of NA (0.3 microM). Responses to NA were increased after endothelium removal; however, responses to SNS were unaffected. Serotonin in a concentration which did not itself produce vasoconstriction (100 nM) increased responses of endothelium-intact preparations to NA and SNS and of endothelium-denuded preparations to SNS but had no effect on NA responses of endothelium-denuded preparations. If neuronal uptake was inhibited with cocaine (1 microM), serotonin markedly amplified responses to NA and SNS in both endothelium-intact and endothelium-denuded preparations. These results suggest that the endothelium influences the amplifying effect of serotonin on responses of rabbit ear artery to NA but not to SNS. Inhibition of removal of serotonin and NA by neuronal uptake may extend the facilitatory interaction between NA and serotonin to smooth muscle cells which are not subject to the inhibitory influence of an endothelium derived relaxing factor.


Effect of lipid peroxidation on the accessibility of dansyl chloride labeling to lipids and proteins of bovine myelin.
In our previous studies we have demonstrated that bovine myelin appears highly susceptible to oxidative damage to both its lipid and protein composition. In order to determine whether these alterations would affect the accessibility of myelin components to a fluorescent probe, we have performed various labeling experiments using dansyl chloride. Results from labeling of purified bovine myelin treated with or without cumene hydroperoxide show that basic protein from treated myelin incorporated more dansyl chloride than basic protein from untreated myelin. This increase of labeling could be prevented by the addition of the antioxidant agent, butylated hydroxytoluene. This evidence suggest that lipid peroxidation may play an important role in the pathogenesis of inflammatory demyelinating diseases.


Rheology-determined critical conditions for shear-induced crystallization of biosynthesized polyhydroxyalkanoates.
Shear-induced crystallization plays a crucial role in the manufacturing process of polymers. In this work, crystallization kinetics of biosynthesized polyhydroxyalkanoates (PHA) under different shear conditions were systematically investigated by rheometers. First, rheological properties of PHA melts were performed at different temperature to obtain mastercurves via the time-temperature superposition principle at 170 °C as a reference temperature. Then the stretch relaxation time and corresponding critical shear rate at different temperatures for the flow regime transition were calculated via the discrete Maxwell relaxation time spectrum and Arrhenius equation. Finally, the influence of shear temperature (Ts), shear time (ts) and shear rate (γ̇) on the crystallization process of PHA were discussed. The results showed the crystallization rate of PHA was improved significantly under high shear rate and long shear time. Interestingly, the t1/2 reached the minimum value when the γ̇ or the ts was large enough, which reached around 450 s at isothermal crystallization condition of 100 °C. Moreover, the nucleation density for PHA increased by appx.100 times than that under quiescent conditions. Therefore, this work may provide a useful theoretical guidance on the shear-induced crystallization of PHA.


A functional polymorphism within the mu-opioid receptor gene and risk for abuse of alcohol and other substances.
Genetic association studies investigating the role of the +118A allele of the human mu-opioid receptor gene in risk for alcohol dependency have produced inconsistent findings, possibly because of the failure to recognize sampling methodology difficulties inherent in association studies of polygenic disorders. We examined the frequency of the AA genotype and A allele in several groups of substance-dependent cases, unrestricted controls, and super controls screened for the use of alcohol and cigarettes. Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance. The nature of the conferred risk is likely to be in use of multiple substances, but it is not yet determined if the risk could be expressed in severity of use of any particular substance. The contribution of the gene to risk for substance dependence is small, and is detected most easily in studies that use control samples that are screened for all forms of substance dependence.


The Assembling of Poly (3-Octyl-Thiophene) on CVD Grown Single Layer Graphene.
The interface between organic semiconductor and graphene electrode, especially the structure of the first few molecular layers at the interface, is crucial for the device properties such as the charge transport in organic field effect transistors. In this work, we have used scanning tunneling microscopy to investigate the poly (3-octyl-thiophene) (P3OT)-graphene interface. Our results reveal the dynamic assembling of P3OT on single layer graphene. As on other substrates the epitaxial effect plays a role in determining the orientation of the P3OT assembling, however, the inter-thiophene distance along the backbone is consistent with that optimized in vaccum, no compression was observed. Adsorption of P3OT on ripples is weaker due to local curvature, which has been verified both by scanning tunneling microscopy and density functional theory simulation. Scanning tunneling microscopy also reveals that P3OT tends to form hairpin folds when meets a ripple.


Identification and characterization of a novel beta subunit of soluble guanylyl cyclase that is active in the absence of a second subunit and is relatively insensitive to nitric oxide.
Previously characterized soluble guanylyl cyclases form alpha-beta heterodimers that can be activated by the gaseous messenger, nitric oxide. In mammals, four subunits have been cloned, named alpha1, alpha2, beta1, and beta2. We have identified a novel soluble guanylyl cyclase isoform from the nervous system of the insect Manduca sexta that we have named M. sexta guanylyl cyclase beta3 (MsGC-beta3). It is most closely related to the mammalian beta subunits but has several features that distinguish it from previously identified soluble cyclases. Most importantly, MsGC-beta3 does not need to form heterodimers to form an active enzyme because guanylyl cyclase activity can be measured when it is expressed alone in COS-7 cells. Moreover, this activity is only weakly enhanced in the presence of the nitric oxide donor, sodium nitroprusside. Several of the amino acids in rat beta1 subunits, previously identified as being important in heme binding or necessary for nitric oxide activation, are substituted with nonsimilar amino acids in MsGC-beta3. There are also an additional 315 amino acids C-terminal to the catalytic domain of MsGC-beta3 that have no sequence similarity to any known protein. Northern blot analysis shows that MsGC-beta3 is primarily expressed in the nervous system of Manduca.


Consumer health information technology in an adult public health primary care clinic: a heart health education feasibility study.
To explore the feasibility and short term outcomes of using an interactive kiosk integrated into office flow to deliver health information in a primary care clinic. Fifty-one adults with BMI ≥25 were randomly assigned to use a kiosk with attached devices to receive a six-week healthy eating/weight monitoring (intervention) or general health/BP monitoring (attention-control) program. Outcomes were measured at baseline, 8 weeks (post) and three month follow-up. Participants completed an average of 2.73 weekly sessions, with transportation and time given as limiting factors. They found the kiosk easy to use (97%), liked the touchscreen (94%), and would use the kiosk again (81%). Although there were no differences between groups, the 27 completing all assessments showed reduced weight (p=.02), and decreased systolic (p=.01) and diastolic BP (p<.001) at follow-up. Although healthy eating behaviors increased, the change was not statistically significant. Using a kiosk within a clinic setting is a feasible method of providing health information and self-monitoring. Multi-session educational content can provide beneficial short-term outcomes in overweight adults. A kiosk with attached peripherals in a clinic setting is a viable adjunct to provider education, particularly in medically underserved areas.


Engineering microbial systems for the production and functionalization of biomaterials.
A new trend in biomaterials synthesis is harnessing the production of microorganisms, owing to the low cost and sustainability. Because microorganisms use DNA as a production code, it is possible for humans to reprogram these cells and thus build living factories for the production of biomaterials. Over the past decade, advances in genetic engineering have enabled the development of various intriguing biomaterials with useful properties, with commercially available biomaterials representing only a few of these. In this review, we discuss the common strategies for the production of bulk and commodity biogenic polymers, and highlight several notable approaches such as modular protein engineering and pathway optimization in achieving these goals. We finally investigate the available synthetic biology tools that allow engineering of living materials, and discuss how this emerging class of materials has expanded the application scope of biomaterials.


Primary lipid cardiomyopathy.
In this communication, we describe an isolated, apparently congenital cardiomyopathy (CMP) characterized by the accumulation of stainable lipid in mitochondria of cardiomyocytes. This lesion, which we term primary lipid cardiomyopathy, has not been reported so far. The structural alteration was associated with progressive heart failure, leading to death at the age of 3 years, and with massive hypertrophy of myocardium. Lipid storage in heart muscle cells resulted in an impressive yellow to orange color of the myocardium. We suggest that this type of primary CMP may represent a new member within the group of mitochondrial CMPs. Possible pathogenic mechanisms are discussed.


Medical therapy of chronic heart failure. Role of ACE inhibitors and beta-blockers.
Heart failure has long been considered to have a progressive downhill course leading inexorably to an early demise. This course often occurs silently, in the absence of any obvious cardiac insults. The reason for this is a combination of cell loss, myocyte dysfunction, impaired energetics, and pathologic remodeling of the chamber. Improved clinical outcome should result from strategies that reduce the biologic signals responsible for myocyte growth, dysfunction, and loss and chamber remodeling. Clinicians should no longer attempt to treat chronic heart failure with pharmacologic growth and remodeling process. In time, it may be possible for the clinician to view the treatment of heart failure largely as a matter of improving the biologic function of the myocardium.


A standardized, innovative method to characterize the structure of aquatic protein hydrolysates.
The performances of protein hydrolysates highly depend on their peptide composition (amount, size and diversity), which itself closely depends on raw material origin and the hydrolysis parameters of the manufacturing process. The current analyses that characterize protein hydrolysates provide information on the level of hydrolysis (degree of hydrolysis, DH). However, they need additional describers to better characterize peptide profiles and product standardization. To reach this objective, we developed a fast and standardized method to characterize the abundance and the diversity of low-molecular-weight peptides in protein hydrolysates. This method innovatively combines classical HPSEC and nLC-ESI-MS analytical tools to characterize any kind of hydrolysate, whether solid or liquid, in terms of peptide level and diversity, and then merge peptides into 2D diagrams to visualize comparisons between protein hydrolysates. The targeted applications of this new tool for characterizing complex protein hydrolysates are (i) verifying the standardization of the produced products across batches, and (ii) analyzing and understanding the consequences of the modifications of the hydrolysis process on the molecular profiles of the generated peptides. The sample standardization described in this study is therefore an essential prerequisite for the functional characterization of hydrolysates in vitro.


Neutralization of hemostatic disorders induced by Lachesis muta venom using Brazilian antivenoms.
We characterized the hemorrhagic, coagulant and defibrinogenant activities of Lachesis muta venom and evaluated the capacity of the Brazilian antivenoms in neutralizing these activities. The hemorrhagic activity of L. muta venom was similarly neutralized by Bothrops, Bothrops-Lachesis and Bothrops-Crotalus antivenoms. The coagulant and defibrinogenant activities were better neutralized by the Bothrops-Lachesis antivenom. Bothrops-Crotalus antivenom also neutralized these activities, indicating that it can be an alternative to treat Lachesis envenomations when Bothrops-Lachesis antivenom is unavailable.


Prevalence of type 2 diabetes and pre-diabetes in Sri Lanka: a systematic review and meta-analysis.
The purpose of this research was to determine the prevalence of diabetes and pre-diabetes in Sri Lanka. Systematic review and meta-analysis. MEDLINE (via PubMed), Web of Science, Sri Lankan Journals online and Google Scholar were searched for relevant articles published between January 1990 and June 2022 investigating the prevalence of pre-diabetes and diabetes in Sri Lanka. Random effect meta-analyses were conducted to derive the pooled prevalence of pre-diabetes and diabetes and their 95% CIs. Heterogeneity was explored by subgroup and meta-regression analyses. Sensitivity analyses were used to evaluate the impact of any single study on the pooled estimates. Two authors screened articles, extracted data and evaluated the quality of selected studies. A total of 479 articles were reviewed, and 15 studies (n=30 137 participants) were selected in the final analysis. The overall pooled prevalence of diabetes was 12.07% (95% CI, 8.71% to 15.89%; prediction interval: 1.28-31.35). The pooled pre-diabetes prevalence was 15.57% (95% CI, 9.45% to 22.88%; prediction interval: 0.02-49.87). The pooled type 2 diabetes prevalence was the highest in the latest period of 2011-2021 (17.25%) than in the period of 2000s (11.84%) and 1990s (5.62%). The growing trend of diabetes and pre-diabetes over the last 30 years is alarming in Sri Lanka. The government of Sri Lanka needs to take steps to improve diabetes education, screening, diagnosis and treatment. CRD42021288591.


Accessibility of cellulose: Structural changes and their reversibility in aqueous media.
During various processing treatments, the accessibility of cellulose in cellulosic fibers reduces, which is often interpreted as cellulose microfibril aggregation. This affects the reactivity of cellulose in further processing to novel cellulosic products such as nanocellulose. In this study, the effect of aqueous treatments at elevated temperatures and various pH on accessibility of an oxygen delignified eucalyptus kraft pulp was evaluated by using deuteration combined with Fourier-transform infrared (FT-IR) spectroscopy and water retention value (WRV) test. Acidic treatments reduced WRV and caused irreversible deuteration of the pulp. However, alkaline treatments increased WRV and caused reversible deuteration of the pulp. Both deuteration and reprotonation of the deuterated pulp followed the same slow, first-order dynamics. This led us to propose that incubation of alkaline cellulosic pulp suspensions at elevated temperatures does not only lead to reduction in accessibility but also to a dynamic interconversion between accessible and inaccessible regions.


The challenge of dissecting gene function in model organisms: Tools to characterize genetic mutants and assess transcriptional adaptation in zebrafish.
Genome editing technologies including the CRISPR/Cas9 system have greatly improved our knowledge of gene function and biological processes, however, these approaches have also brought new challenges to determining genotype-phenotype correlations. In this chapter, we briefly review gene-editing technologies used in zebrafish and discuss the differences in phenotypes that can arise when gene expression is inhibited by anti-sense or by gene editing techniques. We outline possible explanations for why knockout phenotypes are milder, tissue-restricted, or even absent, compared with severe knockdown phenotypes. One proposed explanation is transcriptional adaptation, a form of genetic robustness that is induced by deleterious mutations but not gene knockdowns. Although much is unknown about what triggers this process, its relevance in shaping genome expression has been shown in multiple animal models. We recently explored if transcriptional adaptation could explain genotype-phenotype discrepancies seen between two zebrafish models of the centrosomal protein Cep290 deficiency. We compared cilia-related phenotypes in knockdown (anti-sense) and knockout (mutation) Cep290 models and showed that only cep290 gene mutation induces the upregulation of genes encoding the cilia-associated small GTPases Arl3, Arl13b, and Unc119b. Importantly, the ectopic expression of Arl3, Arl13b, and Unc119b in cep290 morphant zebrafish embryos rescued cilia defects. Here we provide protocols and experimental approaches that can be used to explore if transcriptional adaptation may be modulating gene expression in a zebrafish ciliary mutant model.


Fluorescent staining of nuclei and amyloid substance. Two useful properties of p-phenylenediamine.
Mounting immunofluorescent slides in an oxidized solution of p-phenylenediamine in 90% glycerol, resulted in brown fluorescent staining of nuclei. This contrasts well with the fluorescence of fluorescein and rhodamine conjugates and facilitates excellent morphological localization of antigens. The antifading effect of p-phenylenediamine is maintained in this oxidized solution. In addition, amyloid substance gives a bright yellow-orange fluorescence with this medium. This method of staining is more sensitive and less time consuming than the usual methods for amyloid. Alternative techniques to keep the antifading effect without either nuclear or amyloid counterstain (for identification of nuclear antigens), or to show up amyloid deposits without nuclear counterstain (for small amyloid deposits) are described.


Design and chemical synthesis of a 32 residues chimeric microprotein inhibiting both trypsin and carboxypeptidase A.
A chimeric peptide, 32 amino acids long, bearing two active sites, one inhibiting trypsin (Kd = 1.8 10(-9) M), one carboxypeptidase A (Kd = 3 10(-9) M), was designed and synthesized. It is a "squash inhibitor" (EETI II, 28 amino acids) elongated with the 4 amino acids from the C-terminus of the potato carboxypeptidase inhibitor. It has 3 disulfide bridges assembled in the particular knotted topology shared by the two inhibitors, by conotoxin omega, and possibly by E. coli enterotoxin ST1b.


Clinical observation of tear film breakup time with a novel smartphone-attachable technology.
To demonstrate the practicability of a portable instrument in assessing tear film breakup time (TFBUT): a lens attachment for smartphones (LAS). By applying LAS in combination with the iPhone 12 pro, and a recordable slit-lamp microscope, we obtained TFBUT videos from 58 volunteers. The comparison between the conventional slit-lamp microscope and LAS by an experienced ophthalmologist. Moreover, we also invited an ophthalmic postgraduate student and an undergraduate student with no clinical experience to assess TFBUT in those videos. The inter-observer reliability was assessed using intraclass correlation coefficients (ICC). The TFBUT of 116 eyes in total was recorded. Reliability indexes were adequate. The Spearman's correlation analysis and the intraclass correlation coefficient suggested a strong correlation between the 2 modalities (Right eye: Spearman's r = 0.929, 95% confidence interval (CI) = 0.847-0.963, ICC = 0.978, p < 0.001; Left eye: Spearman's r = 0.931, 95% CI = 0.866-0.964, ICC = 0.985, p < 0.001;). Between instruments, the majority of TFBUT measurements showed good agreement on Bland Altman plot. A high concordance was observed in TFBUT, when assessed by an ophthalmologist and an ophthalmic postgraduate student (Left eye: LAS ICC = 0.951, p < 0.001; Left eye: slit-lamp microscope ICC = 0.944, p < 0.001). Compared with the conventional slit-lamp microscope, the LAS has sufficient validity for evaluating TFBUT in clinics or at home.


Experience of silicone gel sheets for patients with keloid scars after median sternotomy.
It is often difficult to control hypertrophic scars and keloids with drug therapy, steroid injection, surgery, radiation therapy, laser, or wound pressing. Use of silicone gel to treat hypertrophic burn scars and fresh incisions has yielded encouraging results. We report our experience of silicone gel sheets for patients with keloids following median sternotomy. Nine patients underwent a median sternotomy and received other therapies before participating in this treatment. A silicone gel sheet was placed directly on the keloid scar and maintained at all times. Sheets were replaced every 4 weeks for a total treatment duration of 24 weeks. The scar area was measured, and subjective symptoms were determined prior to therapy and after completion of therapy. There were three men and six women, with a mean age of 45.2 years (range 22-69 years). Progression of protuberance and rub was seen in one patient. Scar redness and cramping were either diminished or unchanged in all patients. Itching progressed in two patients. After 6 months, the area of the scar relative to its initial area was 0.98 (range 0.78-1.27). Harmful events did not occur. A silicone gel sheet is effective for treating keloid scars following median sternotomy. Silicone gel sheets are safe and easy to use and do not aggravate any subjective symptoms.


Calcitonin gene-related peptide modulates calcium mobilization in synaptosomes of rat spinal dorsal horn.
Effects of synthetic human calcitonin gene-related peptide (hCGRP) on Ca2+ mobilization in crude synaptosomes prepared from rat spinal dorsal horn were studied using 45Ca2+ as a tracer. hCGRP promoted the influx of 45Ca2+ into synaptosomes of the spinal dorsal horn, in a dose dependent manner (at dose ranges from 10(-9) to 10(-6) M). The maximum effect of hCGRP on 45Ca2+ influx was achieved 5 min after addition of the peptide and was significantly inhibited by nifedipine. hCGRP did not alter the influx of 45Ca2+ into synaptosomes of the rat cerebral cortex, a brain area with reportedly few CGRP binding sites. In measurements of the 45Ca2+ efflux from synaptosomes of the spinal dorsal horn, 10(-7) M of hCGRP had no effect on the efflux of 45Ca2+ from the resting synaptosomes, but there was significant inhibitory effect on synaptosomes depolarized by 40 mM K+. The inhibitory effect of hCGRP on the efflux of 45Ca2+ was completely abolished by lowering the incubation temperature of the medium to 0 degrees C. The inhibitory effect of hCGRP on the efflux of 45Ca2+ was not observed in synaptosomes of the cerebral cortex. These findings suggest that hCGRP increases the levels of Ca2+ level in synaptosomes of the spinal dorsal horn, through interactions with its own receptors and the release of neurotransmitters from the nerve terminals is thus enhanced.


Relationships between glutamate release, blood flow and spreading depression: real-time monitoring using an electroenzymatic dialysis electrode.
Spreading depression (SD) in a flow-restricted area of the brain may be prolonged and may become potentially harmful by releasing glutamate. We induced SD in an oligemia model and examined the subsequent glutamate release. In 18 anesthetized male Fischer rats, a laser Doppler flowmeter, an electroenzymatic electrode for continuous measurement of glutamate, and a calomel electrode for measuring DC potential were placed through a cranial window positioned 3 mm away from a second window where KCl-soaked cotton was placed to initiate SD. The left carotid artery or both the common carotid arteries were ligated to suppress reactive hyperemia of SD. SD produced an increase in glutamate from 24.8 +/- 13.8 to 33.5 +/- 25.3 microM (peak value) (P < 0.0001). After ligation of both carotid arteries, the duration of SD increased from 1.5 +/- 0.6 min (before ligation) to 6.4 +/- 5.1 min (P < 0.05). Glutamate reached a peak level of 63.9 +/- 72.3 microM, then quickly returned to the control value. However, there was no positive correlation between the duration of SD and glutamate concentration. It is concluded that prolonged SD is not accompanied by a progressive increase in glutamate. Therefore, glutamate release induced by SD may not exert harmful effects on neurons.


Upregulation of the long non-coding RNA, LIPCAR promotes proliferation, migration, and metastasis of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo. The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases.


Association of Type 2 Diabetes Mellitus With Perivascular Spaces and Cerebral Amyloid Angiopathy in Alzheimer's Disease: Insights From MRI Imaging.
According to the amyloid cascade hypothesis, fibrillary amyloid-beta load in the brain causes Alzheimer's disease (AD) with toxic effects. Recently, perivascular spaces (PVSs), fluid-filled cavities around small penetrating arterioles and venules in the brain, and the glymphatic system relationship with type 2 diabetes mellitus (DM2) and AD has been an important research topic from a physiopathological point of view. There are two types of PVSs that are associated with sporadic atherosclerosis and cerebral amyloid angiopathy. In this study, we evaluated the relationship between the number and localization of enlarged PVSs in AD. A total of 254 patients with AD and 125 healthy controls were included in this study All the patients were evaluated with neurological and cognitive examinations and magnetic resonance imaging (MRI). PVSs on MRI were graded by recording their number and location. The study was a retrospective study. In our study, the number of white matter convexity-central semiovale localized PVSs was higher in patients than in the control group. In addition, the number of PVSs in this localization score was higher in patients with DM2. Cerebral PVS counts were higher in patients with AD than in the control group. These results suggest the important role of cerebral amyloid angiopathy, one of the vascular risk factors, and the glymphatic system in the pathogenesis of AD. In addition, the results of our study suggest that the evaluation of PVSs levels, especially at the (centrum semiovale), using imaging studies in AD is a potential diagnostic option.


Serum levels of matrix metalloproteinase-10 are associated with the severity of atherosclerosis in patients with chronic kidney disease.
Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). As matrix metalloproteinases have a major role in atherosclerosis, we hypothesized that alterations in metalloproteinases-8, -10 and their tissue inhibitor-1 can be associated with the severity of atherosclerosis in patients with kidney disease. This was evaluated in a cross-sectional, observational study of 111 patients with stages I-V kidney disease, 217 patients on dialysis and 50 healthy controls. The severity of atherosclerosis was estimated with the atherosclerosis score (AS), combining the results of ankle-brachial index and carotid ultrasound. Serum levels of the two metalloproteinases and tissue inhibitor-1 were measured by enzyme-linked immunosorbent assay and were significantly increased in patients with kidney disease compared with the healthy controls, and higher in patients on dialysis than in earlier stages of CKD. The severity of the AS was also more prevalent in the dialysis group, in which serum levels of both metalloproteinases and tissue inhibitor-1 were significantly higher. After multivariate analysis, metalloproteinase-10, dialysis, C-reactive protein, age, and male gender were associated with increased risk of atherosclerosis. Thus, patients with CKD exhibit elevated levels of circulating metalloproteinase-10, and this was independently associated with the severity of atherosclerosis and may represent a new biomarker of atherosclerotic diseases.


[Vasodepressor syncopes in metastasizing laryngeal cancer. Combination therapy using an AV sequential pacemaker and ephedrine].
Syncope due to hypersensitivity of carotid sinus developed in a patient with laryngeal carcinoma. After implantation of a ventricular demand pacemaker a marked vasodepressor component became evident leading to further episodes of fainting. Only after implantation of an AV-sequential pacemaker and additional oral medication with ephedrine syncopes could be prevented.


Clinical characteristics of nosocomial norovirus outbreaks in Hong Kong.
Norovirus outbreaks occur worldwide every year and have become more frequent over the last few years. There were extensive outbreaks in Hong Kong from May to July 2006 and our aim was to describe nosocomial outbreaks from 1 May 2006 to 31 July 2006 in this retrospective observational study. A total of 38 confirmed norovirus outbreaks involving 218 patients were identified. Most of these patients were elderly with a mean age of 74.5 years (range: 3 months to 97 years); 62% of them were either totally or partially dependent for help with daily activities, 83.9% had underlying chronic medical problems and 56% had limited mobility. In all, 97.2% of individuals presented with diarrhoea and only 46.3% of them had vomiting. The median duration for diarrhoea was 3 days and the longest 24 days. The median duration of vomiting was one day and the longest 15 days. Fever occurred in one-third of all cases. Reverse transcriptase-polymerase chain reaction was positive for norovirus in 72.6% cases. We conclude that nosocomial norovirus infection often involves frail elderly patients with limited mobility and that these patients may have more prolonged symptoms.


5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder.
The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD. Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence. Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence. These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD.


Identification and dynamics of Arabidopsis adaptor protein-2 complex and its involvement in floral organ development.
The adaptor protein-2 (AP-2) complex is a heterotetramer involved in clathrin-mediated endocytosis of cargo proteins from the plasma membrane in animal cells. The homologous genes of AP-2 subunits are present in the genomes of plants; however, their identities and roles in endocytic pathways are not clearly defined in plants. Here, we reveal the molecular composition of the AP-2 complex of Arabidopsis thaliana and its dynamics on the plasma membrane. We identified all of the α-, β-, σ-, and μ-subunits of the AP-2 complex and detected a weak interaction of the AP-2 complex with clathrin heavy chain. The μ-subunit protein fused to green fluorescent protein (AP2M-GFP) was localized to the plasma membrane and to the cytoplasm. Live-cell imaging using a variable-angle epifluorescence microscope revealed that AP2M-GFP transiently forms punctate structures on the plasma membrane. Homozygous ap2m mutant plants exhibited abnormal floral structures, including reduced stamen elongation and delayed anther dehiscence, which led to a failure of pollination and a subsequent reduction of fertility. Our study provides a molecular basis for understanding AP-2-dependent endocytic pathways in plants and their roles in floral organ development and plant reproduction.


The Functional Aspects of Resting EEG Microstates: A Systematic Review.
A growing body of clinical and cognitive neuroscience studies have adapted a broadband EEG microstate approach to evaluate the electrical activity of large-scale cortical networks. However, the functional aspects of these microstates have not yet been systematically reviewed. Here, we present an overview of the existing literature and systematize the results to provide hints on the functional role of electrical brain microstates. Studies that evaluated and manipulated the temporal properties of resting-state microstates and utilized questionnaires, task-initiated thoughts, specific tasks before or between EEG session(s), pharmacological interventions, neuromodulation approaches, or localized sources of the extracted microstates were selected. Fifty studies that met the inclusion criteria were included. A new microstate labeling system has been proposed for a comprehensible comparison between the studies, where four classical microstates are referred to as A-D, and the others are labeled by the frequency of their appearance. Microstate A was associated with both auditory and visual processing and links to subjects' arousal/arousability. Microstate B showed associations with visual processing related to self, self-visualization, and autobiographical memory. Microstate C was related to processing personally significant information, self-reflection, and self-referential internal mentation rather than autonomic information processing. In contrast, microstate E was related to processing interoceptive and emotional information and to the salience network. Microstate D was associated with executive functioning. Microstate F is suggested to be a part of the Default Mode Network and plays a role in personally significant information processing, mental simulations, and theory of mind. Microstate G is potentially linked to the somatosensory network.


The normal and abnormal growth plate.
Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities.


A problem-oriented gynecology clinic for patients with sexually transmitted diseases.
A problem-oriented clinic designed to provide continuity of care for female patients with sexually transmitted diseases (STDs) is described. The primary goal of the clinic is to ensure adequate follow-up care for individuals diagnosed as having pelvic inflammatory disease. Functions of the clinic also include follow-up care for patients with positive gonorrhea cultures and consultation for individuals with other STDs. From the time of initiation of the clinic in January, 1976, until November 15, 1979, 4,305 patients were seen. A stratified random sample of 190 of these patients revealed the reasons for attending the clinic to be: (1) follow-up for PID, 85 patients (44.7%), (2) positive gonorrhea culture, 63 (36.3%), (3) unsatisfactory gonorrhea culture, 14 (7.4%), (4) gonorrhea contact, 10 (5.3%), and (5) other, 12 (6.3%). Complete follow-up has been obtained on 3,935 (91.4%) of the patients. Of the 370 patients who did not return for follow-up visits, 336 were reported to the local health department for retrieval. There were 34 patients in whom the follow-up status could not be determined. The establishment, operation, advantages, and disadvantages of the clinic are discussed.


[Nodular granuloma of the lip. An unusual manifestation of secondary syphilis].
Syphilis is a sexually transmitted disease caused by Treponema pallidum which evolves through three overlapping stages. A 50-year-old woman presented with an expanding painless granulomatous nodule on her lower lip in combination with a maculo-papular exanthem. Both serologic studies and microscopic examination indicated an infection with Treponema pallidum. This case shows an unusual granulomatous nodular presentation of syphilis on the lower lip, emphasizing the variable clinical and histological manifestations syphilis, which shows an increasing number of new infections worldwide in recent years.


Molecular epidemiology of avian bornavirus from pet birds in Japan.
Recently, Avian bornavirus (ABV) was detected in proventricular dilatation disease (PDD) affected-birds and feather picking diseases affected-birds. However, the pathogenicity of ABV has not been thoroughly investigated. In this study, we surveyed ABV in pet birds in Japan. We found four ABV-infected birds among 93 pet birds using RT-PCR, and genotypes of the ABV were determined as ABV-2 and -4. Two of the birds positive for ABV-4 showed proventricular dilatation typically found in PDD, and chronic stomach disturbance, whereas two of the birds positive for ABV-2 showed unexplained behavioral problems that are tapping, autophagia, and cloaca prolapse.


Having Infants in the Family Group Promotes Altruistic Behavior of Marmoset Monkeys.
The common marmoset (Callithrix jacchus) has attracted much attention as a useful model for studying social behaviors [1-3]. They naturally live in a monogamous family group and exhibit cooperative breeding [4], in which parents and older siblings help to carry infants less than 2 months old [5-7]. Marmoset parents also transfer foods to their offspring, a process that may help them learn the food diet [8]. Furthermore, marmosets show spontaneous altruistic behaviors, such as providing food to non-reciprocating and genetically unrelated individuals [9]. These social habits indicate that marmosets may be a useful non-human primate model for studying parenting and altruistic behaviors, as well as underlying neural mechanisms. Using a novel rescue paradigm, we found that marmoset parents and older siblings showed strong motivation to rescue trapped young infants but not juvenile marmosets beyond 2 months of age, and infant calls alone could trigger these parents' rescue behaviors. The marmoset parents showed little rescue of each other, but young infants or infant calls could also induce such parents' mutual rescue. Moreover, all these infant- and mate-rescue behaviors depended on currently having young infants in the family group. Functional MRI studies on awake adult marmosets showed that calls from young infants, but not juvenile marmosets, elicited a large-scale activation of specific brain areas including auditory and insular cortices, and such activation was absent in marmosets not living with infants. Thus, such infant-induced modification of neural activity offers a window for examining the neural basis of altruistic behaviors in marmoset monkeys.


Comparative study of the elasticity and memory of intraocular lens loops.
The elasticity and memory of intraocular lens loops was tested by manufacturing lenses with matching physical properties but with loops of either polypropylene or VS-100 polymethylmethacrylate (PMMA). After establishing the reliability of measurements, these lenses were compressed under physiologic conditions for up to three years. The rates and extent of reexpansion of the loops were then measured. Given loops of equivalent initial flexibility, VS-100 PMMA has less long-term tendency to reexpand to its initial shape than polypropylene.


The value of practice: A critique of interactional expertise.
Collins and Evans have proposed a 'normative theory of expertise' as a way to solve the 'problem of demarcation' in public debates involving technical matters. Their argument is that all citizens have the right to participate in the 'political' phases of such debates, while only three types of experts should have a voice in the 'technical' phases. In this article, Collins and Evans' typology of expertise--in particular, the idea of 'interactional expertise'--is the focus of a detailed empirical, methodological and philosophical analysis. As a result, we reaffirm the difference between practitioners and non-practitioners, contesting the four central claims about interactional expertise--namely, that (1) the idea of interactional expertise has been proven empirically, (2) it is possible to develop interactional expertise through 'linguistic socialization alone', (3) the idea of interactional expertise supports the 'the minimal embodiment thesis' that the individual human body or, more broadly, 'embodiment' is not as relevant as linguistic socialization for acquiring a language and (4) interactional experts have the same linguistic fluency, understanding and judgemental abilities of practitioners within discursive settings. Instead, we argue, individuals' abilities and understandings vary according to the 'type of immersion' they have experienced within a given practice and whether they bring with them another 'perspective'. Acknowledging these differences helps with demarcation but does not solve the 'problem of demarcation'. Every experience is perspectival and cannot handle, alone, the intertwined and complex issues found in public debates involving technical matters. The challenge, then, concerns the ways to mediate interactions between actors with distinct perspectives, experiences and abilities.


Correlation between clinical/neurophysiological findings and quality of life in Charcot-Marie-Tooth type 1A.
Quality of life (QoL), as defined by the Short Form 36, has previously been shown to be abnormal in patients with Charcot-Marie-Tooth disease (CMT), both for Physical Composite Scores (PCS) and Mental Composite Scores (MCS). We have now extended these observations in a multicenter evaluation of 89 patients with Charcot-Marie-Tooth disease type 1A, the most common form of CMT. Both the PCS and MCS were abnormal also in this cohort, compared with the Italian population at large. In particular, the ability to ambulate independently as well as toe and heel walk correlated well with QoL measures in our patients.


Mutagenicity of 1,2-dichloroethane and 1,2-dibromoethane in two human lymphoblastoid cell lines.
1,2-Dichloroethane (DCE) and 1,2-dibromoethane (DBE) were tested for the ability to induce gene mutations in two human lymphoblastoid cell lines, designated AHH-1 and TK6. Both chemicals were 'direct-acting' mutagens in both cell lines. DBE was essentially equally mutagenic in TK6 cells and AHH-1 cells. In contrast, DCE was 25-fold more mutagenic in the AHH-1 cell line than in the TK6 cell line. This differential sensitivity between AHH-1 cells and TK6 cells was related to the levels of glutathione S-transferase activity in these two cell lines.


Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci.
Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using FAIRE-seq approach supported by transmission electron microscopy. We identified differences in T. cruzi genome compartments, putative transcriptional start regions, and virulence factors. In addition, we also detected a developmental chromatin regulation at tRNA loci (tDNA), which could be linked to the intense chromatin remodeling and/or the translation regulatory mechanism required for parasite differentiation. We further integrated the open chromatin profile with public transcriptomic and MNase-seq datasets. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.


Statistical evaluation of the medium components for the production of high biomass, α-amylase and protease enzymes by Piriformospora indica using Plackett-Burman experimental design.
Piriformospora indica, a member of basidiomycota is an axenically cultivable endophytic fungus which exerts plant growth promoting effects on its host plant. P. indica is known to produce α-amylase and protease. Since the organism exhibits beneficial role in plant growth promotion, achieving high biomass is immensely essential. Hence to enable the commercial production, screening of medium components is a necessary step. The present paper investigates the screening of medium components using Plackett-Burman experimental design wherein the parameters such as α-amylase, protease and biomass have been examined. The parameters α-amylase, protease and biomass was found to vary from 0.25 to 0.45 mg-1 ml-1 min-1, 0.1 to 0.15 mg-1 ml-1 h-1 and 0.8 to 22.6 g l-1, respectively, in 16 runs which demonstrates the strong influence of the medium components.


Difficult denture patients: observations and hypothesis.
The similarities between the HRC and the DDP have been presented. The HRC has been described by many investigators in the psychoanalytic literature. Indications are that both the HRC and the DDP are working through the same mechanism. The similarities are as follows: Both types of patients are driven by a need to seek treatment from someone they will ultimately reject. A self-fulfilling prophecy develops as a cycle leading to failure. Due to lack of trust and a desire to feel important, the patient creates an atmosphere that leads to discord, hostility, anger, and frustration. Resultant discord leads to the establishment of a relationship that demands much time and energy from the helper. The helper is ultimately manipulated into a no-win situation that ends with the helper dismissing the patient, thereby completing the patient's self-fulfilling prophecy. Recurrent stress in the patient's life recycles the drive force and the need for treatment and attention starts all over again. With greater understanding of the DDP's problems, management solutions could be formulated. Management techniques might include an initial interview with trust-building strategies, the reassurance to the patient of the uniqueness of his situation to neutralize the need to create a crisis for his own identity; and challenges to point out the hopelessness of their position to activate the patient's need to prove the helper wrong. Finally, in addition to management of the patient, techniques can be developed to identify the DDP with HRC tendencies. Proper recognition and diagnosis before treatment begins can prevent many problems associated with these patients and prevent stress and discord for both dentist and patients.


Dietary fiber and protein: nutritional therapy in chronic kidney disease and beyond.
The health benefits of dietary fiber in the general population are increasingly recognized. Krishnamurthy et al. provide compelling evidence that chronic kidney disease (CKD) further augments these benefits. CKD, besides a microinflammatory state, is a state of increased proteolytic fermentation. Both these harmful conditions are exacerbated by dietary protein and reversed by dietary fiber. Future nutrition guidelines should consider recommending a higher consumption of dietary fiber or potassium-free alternatives such as prebiotics in CKD patients.


A bedtime dose of ARB was better than a morning dose in improving baroreflex sensitivity and urinary albumin excretion--the J-TOP study.
The hypothesis that the bedtime dosing of angiotensin receptor blocker (ARB) is superior to morning dose in improving baroreflex sensitivity (BRS) and urinary albumin/creatinine ratio (UACR) was tested in this study. Baroreflex sensitivity was measured at baseline and at 6th month (N = 109) and was found to increase in the bedtime-dose group (P = .004), but not in the morning-dose group. The correlations between the change in BRS and the change in UACR were insignificant in the morning-dose group (r = 0.17, P = .26), but were significant in the bedtime-dose group (r = -0.29, P = .04). In conclusion, the improvement of BRS could be one of the mechanisms by which bedtime dosing of ARB confers renal protection.


Studies of the primary structure of the capsular polysaccharide from Klebsiella serotype K15.
The capsular polysaccharide of Klebsiella serotype K15 has been investigated mainly by methylation analysis, characterisation of the oligosaccharides obtained by partial acid hydrolysis, periodate oxidation, enzymic degradation, and 1H- and 13C-n.m.r. spectroscopy, and shown to have the hexasaccharide repeating-unit 1. The glycan does not contain any pyruvic acetal or O-acetyl substituents. (formula; see text)


A database of US state policies to mitigate COVID-19 and its economic consequences.
Since COVID-19 first appeared in the United States (US) in January 2020, US states have pursued a wide range of policies to mitigate the spread of the virus and its economic ramifications. Without unified federal guidance, states have been the front lines of the policy response. We created the COVID-19 US State Policy (CUSP) database ( https://statepolicies.com/ ) to document the dates and components of economic relief and public health measures issued at the state level in response to the COVID-19 pandemic. Documented interventions included school and business closures, face mask mandates, directives on vaccine eligibility, eviction moratoria, and expanded unemployment insurance benefits. By providing continually updated information, CUSP was designed to inform rapid-response, policy-relevant research in the context of the COVID-19 pandemic and has been widely used to investigate the impact of state policies on population health and health equity. This paper introduces the CUSP database and highlights how it is already informing the COVID-19 pandemic response in the US. CUSP is the most comprehensive publicly available policy database of health, social, and economic policies in response to the COVID-19 pandemic in the US. CUSP documents widespread variation in state policy decisions and implementation dates across the US and serves as a freely available and valuable resource to policymakers and researchers.


X-linked mental retardation with macro-orchidism and marker X chromosomes.
A family with X-linked mental retardation and a marker X chromosome was ascertained by the presence of macro-orchidism in the three institutionalized probands. Verbal evaluation revealed a generalized language disability with commonly occurring articulation errors. The heterozygous females in this family exhibited some reduction in mental ability; the marker X chromosome was demonstrated in both sexes.


Update on Management of the Oral and Maxillofacial Surgery Patient on Corticosteroids.
Corticosteroids have been the cornerstone for treatment of many inflammatory and immune disorders with these beneficial effects well recognized by the medical community. It also possesses many undesirable clinical adverse effects that can occur within 2 weeks of use. Moreover, in the past decade, chronic users of corticosteroids have been linked to skeletal (vertebral and hip) osteoporosis/osteonecrosis with some patients requiring adjunctive antiresprotive medications to counteract fracture prevention. Additionally, two case reports have implicated daily prednisone user to cause osteonecrosis of the mandible. This chapter highlights current adrenal suppression classifications, pathophysiology, drug interactions, and perioperative surgical and anesthesia management.


[Current radiologic aspects of surgical technics for resection of cancer of the rectum].
The aim of this work is to describe the current surgical rectum resection techniques for the treatment of cancer and the corresponding radiological images. The authors emphasize the mechanical, "trans-suture" anastomoses and on the colo anal anastomoses with colic container, which radiologists will have to follow up postoperatively.


Eupalinolide B attenuates lipopolysaccharide-induced acute lung injury through inhibition of NF-κB and MAPKs signaling by targeting TAK1 protein.
Acute lung injury (ALI) is a life-threatening disease characterized by severe inflammatory response, which has no pharmacological therapy in clinic. In this study, we found that eupalinolide B (EB), a sesquiterpene lactone isolated from Eupatorium lindleyanum, significantly ameliorated lipopolysaccharide (LPS)-induced ALI in mice, which manifests as reduction in lung injury score, activity of myeloperoxidase, and release of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). In RAW264.7 murine macrophages, EB effectively inhibited LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) by down-regulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), respectively. Mechanistically, EB not only blocked LPS-induced phosphorylation of inhibitor of nuclear factor kappa B kinase-α/β (IKKα/β), phosphorylation and degradation of inhibitor of nuclear factor-kappa B alpha (IκBα), and phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB) P65, but also suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in vitro or in vivo. Through cellular thermal shift assay and western blotting, EB was demonstrated to target and inactivate transforming growth factor β activated kinase-1 (TAK1), which is an important upstream kinase for the activation of NF-κB and MAPKs pathways. Additionally, EB-mediated actions were markedly abolished by dithiothreitol in LPS-exposed RAW264.7 cells, suggesting a crucial role of the α,γ-unsaturated lactone for the anti-inflammatory activity of EB. In conclusion, our findings showed that EB could effectively alleviate ALI in mice, and attenuate inflammatory response by inhibiting the activation of TAK1, and TAK1-mediated activation of NF-κB and MAPKs cascades.


Corticosteroids in Sarcoidosis.
Corticosteroids are the drug of choice for the treatment of sarcoidosis. Because the natural course of sarcoidosis may be self-limiting and/or cause no long-term harm, treatment is not mandatory. Corticosteroids are usually effective for all forms of sarcoidosis, and they work quickly. However, because of the potential toxicities of corticosteroids, alternative medications often need to be considered. Efforts should be made to minimize the corticosteroid dose while keeping the risk of toxicity as low as possible. This article outlines the indications for corticosteroid therapy for sarcoidosis, discusses various dosing regimens, and suggests when alternative corticosteroid agents should be considered.


Brown Algae (Phaeophyceae) from the Coast of Madagascar: preliminary Bioactivity Studies and Isolation of Natural Products.
Eight species of brown algae (Phaeophyceae) from the coast of Madagascar have been investigated for their chemical constituents. Fucosterol (3) was obtained as the most abundant compound. The brown alga Sargassum ilicifolium was the source for the first isolation of the terpenoid C27-alcohol 1,1',2-trinorsqualenol (1) from marine sources. From S. incisifolium we isolated the highly unsaturated glycolipid 1-O-palmitoyl-2-O-stearidonoyl-3-O-β-D-galactopyranosylglycerol (4) and we report the first full assignment of its (1)H and (13)C NMR data. Apo-9'-fucoxanthinone (8) along with 24-ketocholesterol (5), (22E)-3β-hydroxycholesta-5,22-dien-24-one (6), and saringosterol (7) were obtained from Turbinaria ornata. The crude extracts of all eight species of brown algae exhibited a pronounced antimicrobial activity against the Gram-positive bacteria Bacillus cereus, Staphylococcus aureus, and Streptococcus pneumoniae.


ILRUN, a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice.
Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated-like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. ILRUN encodes a protein that contains a ubiquitin-associated-like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun-deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated-like domain of ILRUN was found to be required for its interaction with PPARα. These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.


Changes of systemic prostacyclin and thromboxane A2 in sodium taurocholate- and cerulein-induced acute pancreatitis in rats.
Systemic prostacyclin and thromboxane A2 production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 micrograms/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2 were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A2 activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.


The initiation and function of Th2 responses during infection with Schistosoma mansoni.
Through experiments in which pro-inflammatory mediators have been neutralized in schistosomeinfected WT and IL-4 -/- mice we have been investigating the nature of the immune response that is required to allow survival during the period of acute disease that accompanies the onset of egg production by the parasitic worms. The developing picture is that of an early pro-inflammatory type-1 like response (characterized by the production of IFN-gamma and TNF-alpha and NO) which in the short term is able to control the deleterious effects on the liver associated with the arrival of the eggs, followed rapidly by a potent egg-induced Th2 response which simultaneously subsumes the role of protecting the liver and downregulates the production of the inflammatory mediators, thereby averting the serious consequence associated with the continued high level production of NO. Current research is directed towards: 1) understanding how pro-inflammatory mediators are protective during schistosomiasis, and 2) elucidating the underlying mechanisms through which the Th response is biased in a Th2 direction following exposure to schistosome eggs.


Multidrug resistance and tumor-initiating capacity of oral cancer stem cells.
Recent studies in several tumors showed that presence of cancer stem like side population (SP) cells are responsible for chemotherapeutic drugs resistance and tumor relapse. In our present study, we have analyzed the role of SP cells in oral squamous cell carcinoma cell (OSCC) line OSCC-77. The oral cancer cell line OSCC-77 was analyzed for the presence of SP cells by FACS using Hoechst 33342 dye exclusion method. Further the FACS-sorted SP and non-SP cells were subjected to drug resistance and sphere formation assays. We identified that the presence of SP cells in OSCC-77 cell line was 3.4%, which was reduced to 0.6% in the presence of verapamil, an inhibitor of ABC transporter. Furthermore, we showed that these SP cells were highly drug-resistant, had increased survival and were highly potent for self-renewal. Also, the clone formation efficiency of SP cells was significantly higher compared to non-SP cells (p<0.01). Our data suggest that cancer stem-like SP cells of OSCC-77 cell line contribute to multidrug resistance and are highly involved in tumor relapse. However, further characterization of SP cells at gene expression level and their signaling pathways might provide new insights into the development of novel anticancer drugs.


Psychosocial adjustment in adolescents with craniofacial anomalies: a comparison of parent and self-reports.
To assess rates of psychosocial adjustment problems in adolescents with craniofacial anomalies (CFAs) and to evaluate the correspondence between adolescent and parent reports of adjustment. Retrospective chart review. Reconstructive plastic surgery department in urban medical center. Sixty-four adolescents aged 14 to 18 years with CFAs and their parents. Child Behavior Checklist, Youth Self-Report. Adolescent and parent reports were compared with published norms. Adolescents with CFAs did not differ from norms on rates of self-reported problems in the clinical range. Parents of sons and daughters with CFAs reported elevations in the clinical range for deficits in social and scholastic competence; parents of daughters also reported higher clinical rates of withdrawn and somatic problems. Correlations between adolescent and parent reports were generally higher than seen in norms, especially for boys. Parents and adolescents did not differ in reported rates of problems in the clinical range. Adolescents with CFAs showed elevated risk for problems with academics and peer relationships; there was limited evidence for clinical levels of other adjustment problems. When parent and adolescent reports differed, parents reported more problems.


The heartbeat counting task largely involves non-interoceptive processes: Evidence from both the original and an adapted counting task.
The heartbeat counting task (HCT) is among the most frequently used measures of interoceptive accuracy (i.e., IAcc). Growing concerns, however, have been raised regarding the validity of this task, as well as the validity of the IAcc scores that are derived from it. In the present study, healthy participants (N = 123) performed both the original task and an adapted version of it that stressed the importance of reporting only their perceptually felt heartbeats. In the original task, we found that participants report relying on three different strategies (i.e., detection of heartbeats in a specific body location, detection of heartbeats in a diffuse way and heart rate estimation) to complete the task. In the adapted task, we found that IAcc scores are drastically reduced (about 50%) when asking participants to avoid relying on non-interoceptive signals and to only report the heartbeats they perceive. These findings confirm that the HCT task is largely contaminated by the influence of non-interoceptive processes. Implications of these findings for research on interoception are discussed.


Mitochondrial signal transduction.
The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS). In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology. This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.


Serum beta 2-microglobulin in malignant lymphoma.
Serum beta 2-microglobulin (S-beta 2m) was measured at diagnosis in 189 patients with malignant lymphoma, all with a normal serum creatinine clearance. The diagnosis was non-Hodgkin's lymphoma (NHL) in 149 patients and Hodgkin's disease (HD) in 40. Among the NHL group, S-beta 2m was raised (greater than 3.0 mg/l) in 15% of patients with Stage I and II and in 65% of those with Stage III and IV. The corresponding frequencies for HD were 11% and 83% respectively. In NHL, a high pretreatment level of S-beta 2m was found to be a poor prognostic sign in all stages. Patients in Stage I and II with an elevated pretreatment level of S-beta 2m had a higher relapse rate than those with normal S-beta 2m. In Stage III and IV patients with initial levels greater than 3.5 mg/l, the survival was significantly shorter than in those with initial values of less than 3.5 mg/l. A lower mean S-beta 2m value was found in Stage III and IV patients who achieved complete remission than in those who did not. Serial determinations of S-beta 2m in 23 patients with NHL showed that increased pretreatment levels became normal when remission was achieved and increased again in relapse. Thus the S-beta 2m provides valuable prognostic information in this group of patients.


Simple but predictive protein models.
The traditional approach to computational biophysics studies of molecular systems is brute force molecular dynamics simulations under the conditions of interest. The disadvantages of this approach are that the time and length scales that are accessible to computer simulations often do not reach biologically relevant scales. An alternative approach, which we call intuitive modeling, is hypothesis-driven and based on tailoring simplified protein models to the systems of interest. Using intuitive modeling, the length and time scales that can be achieved using simplified protein models exceed those of traditional molecular-dynamic simulations. Here, we describe several recent studies that signify the predictive power of simplified protein models within the intuitive-modeling approach.


Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions.
The effect of zinc sulfate on the mRNA expressions in Runx2, osteocalcin, alpha1(I) collagen, insulin-like growth factor-I (IGF-I), transforming growth factor-beta1 (TGF-beta1), osteoprotegerin (OPG), regucalcin, zinc transporter 1 (ZIP1), or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) in osteoblastic MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured for 48 h in a medium containing either vehicle or zinc sulfate (10(-6)-10(-4) M) without fetal bovine serum. Culture with zinc sulfate (10(-5) M) caused a significant increase in Runx2, OPG, or regucalcin mRNA expressions in the cells, while it did not have a significant effect on osteocalcin, alpha1(I) collagen, IGF-I, TGF-beta1, ZIP1, or G3PDH mRNA expressions. The effect of zinc sulfate (10(-4) M) in increasing Runx2 mRNA expression was seen at 24-72 h after culture. A significant increase in OPG mRNA expression was observed at 24 or 48 h after culture. Regucalcin mRNA expression was significantly increased at 48 or 72 h after culture with zinc sulfate (10(-4) M). The stimulatory effects of zinc sulfate on Runx2, OPG, or regucalcin mRNAs were significantly prevented in the presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (10(-6) M), an inhibitor of transcription activity. Culture with beta-alanyl-L-histidinato zinc (10(-5) M) caused a significant increase in Runx2 or regucalcin mRNA expressions, while zinc acexamate (10(-5) M) did not have a significant effect on Runx2, OPG, ZIP1, or regucalcin mRNA expressions. This study demonstrates that zinc sulfate has a role in the enhancement of Runx2, OPG, or regucalcin mRNA expression in osteoblastic cells in vitro, suggesting its role in the regulation of gene expression in the cells.


In HIV-positive patients, myeloid-derived suppressor cells induce T-cell anergy by suppressing CD3ζ expression through ELF-1 inhibition.
During HIV infection, a down-modulation of CD3ζ was found on T cells, contributing to T-cell anergy. In this work, we studied the correlation between myeloid-derived suppressor cells (MDSC) frequency and T-cell CD3ζ expression. Moreover, we investigated the mechanisms of CD3ζ decrease exploited by MDSC. CD3ζ expression and MDSC frequency were evaluated by flow cytometry on peripheral blood mononuclear cells from 105 HIV-positive (HIV+) patients. The role of MDSC in the modulation of the HIV-specific T-cell response was evaluated. The level of CD3ζ mRNA and ELF-1 protein were analysed by real-time-PCR and western blot, respectively. We found that granulocytic-MDSC (Gr-MDSC) were expanded in HIV+ patients compared with healthy donors; in particular, in cART-treated individuals a higher Gr-MDSC frequency was observed in patients with a CD4 T-cell count below 400 cells/μl. We found an inverse correlation between the percentage of Gr-MDSC and CD3ζ level. Moreover, in-vitro MDSC depletion induced the up-regulation of CD3ζ in T cells, restoring the functionality of αβ, but not γδ T cells. The in-vitro effect of isolated MDSC on CD3ζ expression was found cell contact-dependent, and was not mediated by previously described molecules. CD3ζ down-modulation corresponds to the decrease of its mRNA induced by silencing the transcription factor ELF-1. Our data provide new knowledge on mechanisms used by Gr-MDSC in immune-modulation and on their role in the immune reconstitution during antiviral treatments.


Effects of chromic acid exposure on immunological parameters among electroplating workers.
To investigate the immunological parameters of chromic acid exposure among electroplating workers. Forty-six subjects were selected from five electroplating plants in central Taiwan. Each subject was interviewed by questionnaire, and urine chromium (urine-Cr) concentration was assessed. Immunological parameters were evaluated by interleukin (IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma) and levels of lymphocyte subsets (T-cell, B-cell, T4, T8 and T4/T8). Levels of IL-6 and IL-8 significantly increased in subjects with high urine Cr concentration, but TNF-alpha levels decreased. IL-2, IL-4, IL-10 and IFN-gamma were undetected. Flow cytometry was used to determine levels of lymphocyte subsets: only B-cells percentage had a negative correlation with urine-Cr. Smoking was an important factor that influenced levels of lymphocyte subsets. Exposure to Cr has a detrimental effect on the immune system, so it is evident that worker exposure to chromic acid in the electroplating workplace must be reduced to a minimum.


In vitro antagonism between cisplatin and vinca alkaloids.
The effects of the combination of cisplatin and other cytotoxic agents were studied in vitro. When A549 lung cancer cells were treated simultaneously with cisplatin and other cytotoxic agents, cisplatin additively increased the cytotoxic effects of etoposide, mitomycin C, adriamycin, 5-fluorouracil and 1-beta-D-arabinofuranosylcytosine, but antagonised those of vincristine, vindesine, vinblastine and podophyllotoxin. The antagonism between cisplatin and vincristine was also observed with HT29 colon cancer cells. NC65 renal carcinoma cells and A431 epidermoid carcinoma cells when these cells were simultaneously exposed to both agents. When A549 cells were exposed to cisplatin and vincristine sequentially, the antagonism between them was evident when cells were pretreated with cisplatin but not when treated in the opposite sequence. Therefore, when combination chemotherapy including cisplatin and vinca alkaloids is given, possible antagonism between them should be considered, especially in determining the schedule of drug administration.


Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, modifies acute seizure burden and chronic epilepsy-related behavioral deficits following Theiler's virus infection in mice.
Temporal lobe epilepsy is the most common form of acquired epilepsy and can arise due to multiple inciting events, including central nervous system (CNS) infection. CNS infection with the Theiler's murine encephalomyelitis virus (TMEV) in male C57Bl/6J mice leads to acute, drug-resistant handling-induced seizures. Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol; the primary mechanism of cholesterol catabolism in the brain. The novel CH24H inhibitor, soticlestat (SOT; or TAK-935), demonstrates the potential to restore excitatory/inhibitory balance in multiple preclinical models of hyperexcitability. This study thus sought to characterize the anticonvulsant potential of SOT in the TMEV model. Treatment with SOT (30 mg/kg, p.o.; n = 30) 0-7 days post-infection (DPI) reduced overall seizure burden and severity. SOT administration significantly delayed onset of infection-induced Racine stage 5 seizures, from 8.6 ± 0.6 (VEH-treated) to 10.8 ± 0.8 (SOT-treated) observation sessions. Infected mice were then allowed 36 days treatment-free recovery before assessing impact of earlier drug administration on epilepsy-related cognitive and behavioral comorbidities, including a non-habituated open field (OF) task. Total OF distance traveled was significantly less in SOT-treated mice compared to VEH-treated mice, suggesting attenuated TMEV-induced spatial memory deficits, or reduced chronic hyperexcitability. Mice with history of SOT treatment also spent significantly more time and traveled farther in the OF center, indicative of reduced epilepsy-induced anxiety-like behavior. These studies suggest that SOT is a mechanistically novel agent for symptomatic seizure control. Moreover, acute SOT administration during an epileptogenic insult may attenuate the resulting long-term behavioral comorbidities of epilepsy.


Cell contact induces the synthesis of a lysosomal enzyme precursor in lymphocytes and its direct transfer to fibroblasts.
The activity of a lysosomal enzyme, alpha-D-mannosidase (EC 22.214.171.124), increased markedly in normal lymphocytes when they were cultured together with fibroblasts from a patient with an inherited deficiency of this enzyme. Cell-to-cell contact was obligatory for this increase in activity, which also required new protein synthesis. The enzyme induced in the co-cultured lymphocytes was a high molecular weight form of alpha-D-mannosidase that was not detected in lymphocytes cultured alone, which had only the low molecular weight mature enzyme. It was this precursor form alone that was directly transferred to the mannosidosis fibroblasts, where it was present initially in organelles of low density. When the culture period was extended the lymphocyte precursor enzyme was transported to the heavy lysosomes in the recipient cells, and correctly processed to the functionally effective mature enzyme.


Age and video capsule endoscopy in obscure gastrointestinal bleeding: a prospective study on hospitalized patients.
The influence of aging on video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) has never been prospectively assessed. To demonstrate if age is a risk factor for incomplete VCE examination in a setting of ongoing hospitalization for OGIB and if it affects the yield of VCE. Forty-eight consecutive patients referred to our unit for obscure-overt GI bleeding from March 2007 to September 2009 were prospectively evaluated. Patients were divided into two groups according to their age: ≤65 years (group A) and >65 years (group B). The VCE completion rate and clinically significant findings were studied. The cecum was reached in 73% of patients. There was no difference between the two groups of patients in the VCE completion rate (78% vs. 68%, P=0.4). The overall diagnostic yield was 61%. A significant difference in the diagnostic yield between group A and group B (45% vs. 75%, P=0.04) was shown. Angiodysplasia was diagnosed in 13 out of 24 (54%) patients of group B, whereas mucosal breaks, such as erosions or ulcers, accounted for over a quarter of the group A findings. Old age is not a risk factor for incomplete VCE examination and it is associated with increased VCE yield.


P3 topography in psychiatry and psychopharmacology.
Endogenous components of event related potentials are of particular interest in psychiatric diseases because of their relations to cognitive and behavioral processes. We studied the topography of these potentials in order to find out whether there are different scalp distributions in schizophrenic and depressive patients in relation to the psychopathological state and compared to normal controls. Furthermore variations of the topographical scalp distribution of P300 in normal volunteers after administration of physostigmine and biperiden was investigated. We demonstrated a clear relationship of the P300 amplitude with the negative symptom axis and found different topographical scalp distributions in different groups and experimental conditions. Topography of event related potentials is therefore a promising field of investigation for a better understanding of psychiatric disorders.


Retraction Note: Formin' a perinuclear actin cage in confined migration.
Given that the authors of 'FMN2 makes perinuclear actin to protect nuclei during confined migration and promote metastasis' (Skau et al. Cell 167, 1571-1585; 2016) have retracted their paper, I wish to retract this Research Highlight, which discussed the findings reported in that study.


Development of endocochlear potential and compound action potential in the rat.
The present study was designed to investigate the developmental changes of the endocochlear potential and compound action potential simultaneously from rat pups of various ages. Animals were anesthetized with ketamine/xylazine, and the endocochlear potential was measured with a glass microelectrode. At the same time, a wire electrode was placed on the round window to record the click-evoked compound action potential. The endocochlear potential was found to be very low during the first few days of postnatal life. A rapid increase in the value of the endocochlear potential was noted between eleven and thirteen days of age, and adult-like values were recorded by seventeen days of age. Compound action potential responses were recorded at thirteen days of age to high intensity clicks, followed by a progressive improvement of thresholds and reduction of latencies. The development of the endocochlear potential and compound action potential was found to be reciprocally related - as the magnitude of the endocochlear potential increased, the compound action potential threshold declined with increasing age. The development of the endocochlear potential was found to closely approximate the development of enzymatic activity of sodium, potassium-ATPase in the stria vascularis reported by Kuijpers (1974).


Interstitial fibrosis in obstructive nephropathy.
Interstitial fibrosis and tubular basement membrane (TBM) thickening are evident within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and resemble the changes previously reported in hydronephrotic human kidneys. The cortical interstitial volume fraction in this rabbit model at 16 days is 43.3 +/- 6.1% (+/- 1 SD) in UUO kidneys, 4.9 +/- 3.1% in contralateral kidneys (CLK), and 2.8 +/- 0.8% in kidneys from sham-operated animals (ANOVA, P < 0.0001). Immunohistochemically, UUO is associated with increased interstitial collagens I and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial nephritis antigen. Aberrant collagen expression is also evident as interstitial collagen IV becomes prominent. Focal, peritubular accumulation of collagens I and II also appear to encircle the TBM. These changes are accompanied by an early, transient increase in renal cortical mRNA encoding the alpha 1 monomers of collagens I, III and IV, implicating increased matrix synthesis in the pathogenesis of obstructive nephropathy. In situ hybridization localized increased expression of alpha 1 (I) and alpha 1 (IV) mRNA to cells in the interstitial space, with clusters of alpha 1(I) positive cells associated with dilated tubules, muscular arteries and the periglomerular interstitium.


Symptoms of eating disorders, drive for muscularity and physical activity among Norwegian adolescents.
The aim of this study was to examine symptoms of eating disorders (ED), drive for muscularity and physical activity in a Norwegian adolescent population. A total of 722 adolescents aged 12-18 years (response rate: 83%) filled out a questionnaire containing the Drive for Muscularity Scale, Eating Disorders Inventory subscales Drive for Thinness (EDI-DT), Body Dissatisfaction (EDI-BD) and Bulimia (EDI-B), and questions about amount of and motives for physical activity. Eating Disorders Inventory subscale scores were higher, and Drive for Muscularity Scale Score (DMS) scores were lower among girls compared with boys. EDI and DMS were correlated with motives for, but not amount of, physical activity. EDI and DMS were associated in boys, not girls. The associations between EDI and DMS among boys call for a wider approach when examining ED among boys.


Ceramic inlays and onlays: clinical procedures for predictable results.
The use of ceramics as restorative materials has increased substantially in the past two decades. This trend can be attributed to the greater interest of patients and dentists in this esthetic and long-lasting material, and to the ability to effectively bond metal-free ceramic restorations to tooth structure using acid-etch techniques and adhesive cements. The purpose of this article is to review the pertinent literature on ceramic systems, direct internal buildup materials, and adhesive cements. Current clinical procedures for the planning, preparation, impression, and bonding of ceramic inlays and onlays are also briefly reviewed. A representative clinical case is presented, illustrating the technique. When posterior teeth are weakened owing to the need for wide cavity preparations, the success of direct resin-based composites is compromised. In these clinical situations, ceramic inlays/onlays can be used to achieve esthetic, durable, and biologically compatible posterior restorations.


The efficient removal of ibuprofen, caffeine, and bisphenol A using engineered egusi seed shells biochar: adsorption kinetics, equilibrium, thermodynamics, and mechanism.
Contaminants of emerging concern (CECs), also known as micropollutants, have been recognized in recent years as substantial water pollutants because of the potential threats they pose to the environment and human health. This study was aimed at preparing biochar (BC) based on egusi seed shells (ESS) with well-developed porosity and excellent adsorption capacity towards CECs including ibuprofen (IBP), caffeine (CAF), and bisphenol A (BPA). BC samples were prepared by pyrolysis at different temperatures (400 to 800 °C) and were characterized using nitrogen sorption, FTIR, powder X-ray diffraction (PXRD), SEM/EDS, elemental analysis, and thermal analysis. The nitrogen sorption and SEM results showed that the textural properties were more prominent as the pyrolysis temperature increased. The BC sample obtained at 800 °C which exhibited the largest specific surface area (688 m2/g) and the highest pore volume (0.320 cm3/g) was selected for the adsorption study of CECs. The kinetic study shows that the adsorption equilibrium of CAF and BPA was faster than that of IBP. The pseudo-first- and pseudo-second-order kinetic models best fitted the adsorption data. The Langmuir maximum monolayer adsorption capacities of biochar were found to be ~ 180, 121, and 73 mg/g respectively for IBP, CAF, and BPA. The thermodynamic study shows that the adsorption process was spontaneous and endothermic for the three CECs. The results of the adsorption and the analysis of BC after adsorption showed that hydrogen bonding, van der Waals, π-π, n-π interactions, and pore filling were involved in the adsorption mechanism. The prepared biochar BC from ESS displayed a large surface area and good morphology and significantly promotes adsorption of CECs and good efficiency on synthetic effluent. Finally, it offers a low-cost and cleaner production method.


No causal relationship between early motherhood and offspring adolescent offending: Empirical evidence from a genetically-informed study.
Previous studies have consistently shown that young maternal age at birth is associated with an increased risk for problematic behavior in offspring. Less is known about the mechanisms underlying this association, as it could either reflect a causal effect or a spurious relationship. This study aims to gain more insights in these underlying mechanisms by studying the relationship between early motherhood and offspring adolescent offending. The sample includes all individuals who were born in the Netherlands between 1991 and 2001 (N=2,098,815). All variables were extracted from register data of Statistics Netherlands, including police registrations to measure adolescent offending. Logistic regression analyses were used to examine the relationship between maternal age at birth and offspring adolescent offending, with and without control variables. Moreover, a children of discordant siblings model was applied to further control for unmeasured familial confounders (i.e., shared environmental and genetic confounders). In line with previous studies, the results show a significant negative relationship between early motherhood and offspring offending. However, no significant effect was found in the children of discordant siblings analysis, which suggests that this relationship is confounded by unmeasured familial factors. These results illustrate the importance of applying genetically informed research designs when studying intergenerational relationships.


Stimuli-responsive peptide nanostructures at the fluid-fluid interface.
The self-organization of peptide-based nanostructures at a confined fluid-fluid interface, for example, the air-water or oil-water interface, is important in the context of stabilizing macroscopic soft-matter foams and emulsions. The unique ability to design interfacial nanostructures by controlling the subtle cooperativity that drives peptide self-assembly, and the ability to switch molecular cooperativity by facile triggers such as pH, opens new vistas for controlling macroscopic soft matter in industries as diverse as healthcare and industrial processing. Here we describe research aimed at developing new understanding into soft-matter formation and control, through variation of peptide sequence and bulk conditions. Macroscopic foaming and microfluidic emulsification studies prove particularly useful in visualizing and hence understanding the synergistic link between molecular design, mesoscopic interfacial properties, and bulk soft-matter stability.