[Binding of Volatile Organic Compounds to Edible Biopolymers].
Capillary gas chromatography was used to study the influence of the composition and structure of different edible polymers (polysaccharides, vegetable fibers, and animal protein gelatin) on the binding of essential oil components. The retention of volatile organic compounds on biopolymers was shown to depend on their molecule structure and the presence, type, and position of a functional group. The maximum extent of the binding was observed for nonpolar terpene and sesquiterpene hydrocarbons, and the minimum extent was observed for alcohols. The components of essential oils were adsorbed due mostly to hydrophobic interactions. It was shown that the composition and structure of a compound, its physico-chemical state, and the presence of functional groups influence the binding. Gum arabic and guar gum were found to bind nonpolar compounds to a maximum and minimum extent, respectively. It was demonstrated the minimum adsorption ability of locust bean gum with respect to all studied compounds.


Application of combined immunohistochemical panel of AMACR(P504S)/p63 cocktail, cytokeratin 5 and D2-40 to atypical glands in prostatic needle biopsy.
Various immunohistochemical studies using cocktail antibodies to elucidate atypical glands in prostatic biopsy specimens have been previously tried. However, there is scanty information on combined cocktail antibodies and other basal cell markers. We investigated the utility of an immunohistochemical panel of AMACR/p63, cytokeratin 5(CK5) and D2-40 for atypical glands in twenty lesions of fourteen patients obtained from prostatic needle biopsy specimens. The final diagnosis of all lesions, including 13 adenocarcinoma demonstrating AMACR+/basal cell(p63, CK5 and D2-40)- pattern, 5 benign lesions noting AMACR-/basal cell+ pattern, and 2 high grade PIN with AMACR+/basal cell+ pattern, were resolved. The immunohistochemical panel of AMACR(P504S)/ p63 cocktail, CK5 and D2-40 is useful in deciding the final diagnosis for atypical gland foci in the prostatic needle biopsy specimens and is helpful in the reduction of opportunity of further followup or re-biopsy.


Delayed recovery of adrenocortical and testicular function after chemotherapy of human trypanosomiasis.
The following indicators of pituitary, adreno-cortical and testicular function were measured in 58 male African trypanosomiasis patients from Western Kenya; plasma cortisol, luteinizing hormone (LH) and testosterone levels. The measurements were carried out by specific radioimmunoassay methods in early and late stage infected patients on admission to hospital and in both groups of patients after one month of chemotherapy. Packed cell volume (PCV) and hemoglobin levels were also measured in all the patients to determine the extent of their anaemia and success of recovery. High parasitaemia, anaemia and clinical symptoms of human trypanosomiasis were found in the infected patients and were eliminated with chemotherapy in the infected/treated patients. Increased levels of cortisol and decreased concentrations of testosterone without significant changes in LH levels were evident in the infected patients; this condition remained unchanged even after one month of chemotherapy. Evidence is thus provided of persistent hormonal perturbations which probably indicate residual endocrine organ damage.


Methodological approaches for dietary intake assessment in formula-fed infants.
The estimation of dietary intake remains a challenge in human nutritional studies. In infants, the use of food diaries (FDs) is a suitable method already validated; however, this method is not exempt from error. In formula-fed infants, dilution of powdered formulas may produce errors. Our aim was to develop and validate standard operating procedures (SOPs) for the assessment of dietary intake in formula-fed infants, attending potential sources of error. We analysed sources of error in a random subsample of 3-day FDs from 100 infants enrolled in the European Childhood Obesity Project. Calculations to estimate intakes were standardised and included in a software tool (SOPsystem). An evaluation of a simulated FD was performed by 9 trained nutritionists and 23 nutrition students (n=225 and n=575 bottle evaluations, respectively) to compare the results obtained when using or not the SOPsystem. Correct answers (%), coefficients of variation, and the time spent (minutes) to assess the simulated FD were analysed. Overall, 60% of the FDs contained reports of incorrect volumes, and 37% reported incorrect formula dilutions. When the SOPsystem was used, correct answers in the simulated FD were more frequent (P<0.001) and the mean coefficient of variation and the time spent were lower (P<0.005 and P<0.01, respectively). The development and implementation of SOPs with a software tool that identifies specific sources of error in record-keeping achieved a harmonised and improved process for assessing dietary intakes in formula-fed infants, minimising errors in calculations and reducing the work time invested.


Confidence Moderates the Role of Control Beliefs in the Context of Age-Related Changes in Misinformation Susceptibility.
Background/Study Context: The present experiment investigated the role of confidence and control beliefs in susceptibility to the misinformation effect in young and older adults. Control beliefs are perceptions about one's abilities or competence and the extent to which one can influence performance outcomes. It was predicted that level of control beliefs would influence misinformation susceptibility and overall memory confidence. Fifty university students (ages 18-26) and 37 community-dwelling older adults (ages 62-86) were tested. Participants viewed a video, answered questions containing misinformation, and then completed a source-recognition test to determine whether the information presented was seen in the video, the questionnaire only, both, or neither. For each response, participants indicated their level of confidence. The relationship between control beliefs and memory performance was moderated by confidence. That is, individuals with lower control beliefs made more errors as confidence decreased. Additionally, the relationship between confidence and memory performance differed by age, with greater confidence related to more errors for young adults. Confidence is an important factor in how control beliefs and age are related to memory errors in the misinformation effect. This may have implications for the legal system, particularly with eyewitness testimony. The confidence of an individual should be considered if the eyewitness is a younger adult.


[Effects of nandrolone decanoate on bone mineral content and intestinal absorption of calcium].
To evaluate the effects of a long-term treatment with nandrolone decanoate on metabolism of the skeleton, a double-blind randomized study was carried out in women with joint diseases without metabolic bone derangement. Ten patients were treated with 50 mg of nandrolone decanoate every three weeks for two years; in six subjects a treatment with placebo was performed. As it concerns plasma calcium and phosphate, serum alkaline phosphatase, urinary excretion of calcium, phosphate, hydroxyproline and cAMP, as parathyroid index, it was not observed significant differences in the two examined groups. While in placebo group at the end of the study the intestinal radiocalcium remained unchanged and bone mineral content showed a slight decrease, on the contrary nandrolone decanoate treatment promoted a significant improvement in intestinal calcium absorption and an increase in bone mineral content.


Conceptual bases of Christian, faith-based substance abuse rehabilitation programs: qualitative analysis of staff interviews.
Faith-based substance abuse rehabilitation programs provide residential treatment for many substance abusers. To determine key governing concepts of such programs, we conducted semi-structured interviews with sample of eleven clinical and administrative staff referred to us by program directors at six, Evangelical Christian, faith-based, residential rehabilitation programs representing two large, nationwide networks. Qualitative analysis using grounded theory methods examined how spirituality is incorporated into treatment and elicited key theories of addiction and recovery. Although containing comprehensive secular components, the core activities are strongly rooted in a Christian belief system that informs their understanding of addiction and recovery and drives the treatment format. These governing conceptions, that addiction stems from attempts to fill a spiritual void through substance use and recovery through salvation and a long-term relationship with God, provide an explicit, theory-driven model upon which they base their core treatment activities. Knowledge of these core concepts and practices should be helpful to clinicians in considering referrals to faith-based recovery programs.


Intestinal ganglioneuromatosis: an unusual aetiology for occult gastrointestinal bleeding.
Intestinal ganglioneuromatosis is a rare disorder of the enteric nervous system. It is often associated with neurofibromatosis type 1 and multiple endocrine neoplasia type 2b but, more rarely, it can present in a sporadic and isolated form. A 66-year-old man presented with a 14-year history of iron deficiency anaemia, with no visible bleeding, requiring occasional blood transfusions. Haematological causes of anaemia were thoroughly excluded, and conventional endoscopic and radiological examinations showed no lesions. Capsule enteroscopy identified an ulcerated stenosis in the small bowel, but the biopsies taken at balloon enteroscopy were inconclusive. The patient underwent a laparotomy, which revealed a stiff and ulcerated stenosis in the ileum. Histological analysis demonstrated the presence of diffuse intestinal ganglioneuromatosis. Three years after surgery, the patient is asymptomatic, with normal haemoglobin levels. This case demonstrates an isolated form of intestinal ganglioneuromatosis, with an atypical presentation, difficult to diagnose despite an exhaustive evaluation.


Preanesthetic nurse communication with children and parents--an observational study.
The impact of communication within the perioperative period is an area of increasing research interest. Suggestions are phrases or actions that can lead to subconscious nonvolitional changes in patient perception, mood, and/or behavior. Statements functioning as suggestions may induce positive or negative perceptual responses and experiences. Children and anxious patients are particularly responsive to the effects of suggestion. We aimed to identify positively and negatively worded statements used during the provision of preoperative information by nursing staff in a tertiary referral center for pediatric care. Audio recordings of preoperative consultations between nurses, children, and their parents were made between February and May 2014. Two researchers independently reviewed the transcripts and identified positively and negatively worded suggestions. Examples of negative suggestions were, 'he is going to be sore for a week or two' or 'normal to feel a bit sick....', and a positive suggestion was 'so she will be feeling quite comfortable...'. There were 51 consultations transcribed and analyzed. Of the 130 suggestions independently agreed by both researchers to be either positive or negative, 40 were identified as positive (31%) and 90 negative (69%). Commonly occurring negative suggestions described: pain in 21 consultations (41%); nausea and sickness in 19 (37%); and irritability or agitation in nine (18%). Positive suggestions included a description of a return of normal activities such as eating and drinking in 14 (28%), comfort in nine (18%), and well-being in nine (18%). Twelve consultations (24%) contained only negative suggestions, while four (8%) had only positive suggestions. This is the first prospective observational study investigating the language used by nurses during the preoperative child-parent encounter. Suggestions for negative perceptual experiences were frequently used during the preoperative nurse consultations. Education of nurses regarding awareness and understanding of negative suggestions and their potential adverse effects is recommended.


Actinomyces naeslundii and Eikenella corrodens as rare causes of liver abscesses.
A 48-year-old man with an unremarkable medical history was admitted with vague conditions of fever, chills, myalgias and malaise. Physical examination was remarkable for only scleral icterus. Laboratory evaluation revealed elevated aminotransferases, alkaline phosphatase and bilirubin. Imaging demonstrated two masses in the right lobe of his liver, which were ultimately drained and cultures demonstrated Actinomyces and Eikenella. He continued to have fever on broad-spectrum antibiotics until catheter drainage of the abscesses was performed. He was eventually discharged in improved condition on amoxicillin-clavulanate. His aminotransferases, alkaline phosphatase and bilirubin continued to improve and he remained afebrile and asymptomatic. A repeat CT 2 months after discharge demonstrated resolution of the abscesses. Actinomyces and Eikenella are rare causes of liver abscesses and treatment requires drainage and an extended course of antibiotics. The polymicrobial character typical of liver abscesses makes antibiotic therapy challenging when cultures reveal rare organisms such as Actinomyces and Eikenella.


Ranibizumab in patients with dense cataract and proliferative diabetic retinopathy with rubeosis.
To evaluate the safety of ranibizumab as a surgical adjunct during cataract surgery in patients with proliferative diabetic retinopathy (PDR) with rubeosis, and to evaluate the efficacy and adverse effects of ranibizumab in treating PDR with rubeosis. Three intravitreal injections of 0.5 mg ranibizumab were administered on day-1, months-1 and -2 with cataract surgery 6-16 days after first injection. Retreatments with ranibizumab injections and pan-retinal photocoagulation (PRP) were given if recurrence or persistence of PDR was noted between months-3 and -11. Safety observation visits occurred at months-12, -18 and -24. Primary end points were incidence and severity of adverse events (AEs) that were related to both cataract surgery and treatment of PDR with rubeosis through month -12. Of six patients screened, four (mean age 61.3 years) were enrolled. No AEs were noted with either cataract surgery or treatment of PDR. Neovascularization of iris (NVI) promptly regressed by 4 days after first ranibizumab injection, prior to cataract surgery in three of four patients (one had significantly regressed NVI by post-injection day-3 visit); NVI was not noted in any patient at 2 weeks after first ranibizumab injection. Recurrence of rubeosis or NVA after 3 monthly injections was not observed in any. At month-12, PDR was not present when assessed clinically and by fluorescein angiogram (FA). Only one patient developed neovascularization of disc and neovascularization elsewhere and required retreatments at months-5 and -9. Multiple intravitreal injections of ranibizumab may be a safe, effective treatment adjunct for PDR and diabetes-related rubeosis.


A sustainability view on the EPR system of N.N. Burdenko Neurosurgical Institute.
This paper aims at the analysis of the "sustainability status" of an electronic patient record system developed at the Medical Informatics Laboratory of the N. N. Burdenko Neurosurgical Institute (EPR/NSI). It includes some of the principles that allowed a small team of developers to create a sustainable EPR system for a large medical institution with complicated diagnostic and treatment processes.


Construction of a recombinant bovine leukemia virus vector for analysis of virus infectivity.
A recombinant bovine leukemia virus (BLV) was constructed in which the X region was replaced with the bacterial neomycin resistance gene controlled by the simian virus 40 early promoter. This virus, termed BLV-SVNEO, is a self-packaging, activator-dependent retroviral vector. Introduction of the plasmid pBLV-SVNEO into mammalian cells resulted in constitutive expression of the neo gene, whereas the BLV structural genes, gag, pol, and env, were expressed only in the presence of the two regulatory proteins, Tax and Rex. The production and release of recombinant virus by cells transfected with pBLV-SVNEO were proportional to the number of G418-resistant colonies that developed after susceptible cells were exposed to the filtered culture medium. BLV-SVNEO was able to infect cell lines of human, bovine, canine, feline, and murine origin. BLV-producing cell lines were resistant to superinfection with BLV-SVNEO. This cell-virus system should facilitate molecular genetic studies of BLV and will provide a rapid, quantitative measure of BLV infectivity in a variety of cell types. These studies also demonstrate the feasibility of using activator-dependent retroviral vectors such as BLV-SVNEO to deliver foreign genes into cells and eventually animals.


Mutants of yeast sensitive to ultraviolet light.
Six uvr mutants of Saccharomyces cerevisiae with hypersensitivity to ultraviolet (UV) light were isolated after mutagen treatment with ethylmethanesulfonate. UV sensitivity ranges from moderate to extreme, and four of the mutants are also sensitive to nitrous acid. Ranking in terms of UV sensitivity does not parallel ranking in terms of nitrous acid sensitivity. Homozygous diploid mutant strains are somewhat less sensitive than the corresponding haploids. All mutations are recessive. None of the mutants is sensitive to gamma rays, and each shows photoreactivation after UV radiation. Complementation tests and tetrad analysis indicate that each strain represents mutation in a different gene. Two of the uvr genes are linked, and two others are centromere-linked.


Biallelic truncating variants in VGLL2 cause syngnathia in humans.
Syngnathia is an ultrarare craniofacial malformation characterised by an inability to open the mouth due to congenital fusion of the upper and lower jaws. The genetic causes of isolated bony syngnathia are unknown. We used whole exome and Sanger sequencing and microsatellite analysis in six patients (from four families) presenting with syngnathia. We used CRISPR/Cas9 genome editing to generate vgll2a and vgll4l germline mutant zebrafish, and performed craniofacial cartilage analysis in homozygous mutants. We identified homozygous truncating variants in vestigial-like family member 2 (VGLL2) in all six patients. Two alleles were identified: one in families of Turkish origin and the other in families of Moroccan origin, suggesting a founder effect for each. A shared haplotype was confirmed for the Turkish patients. The VGLL family of genes encode cofactors of TEAD transcriptional regulators. Vgll2 is regionally expressed in the pharyngeal arches of model vertebrate embryos, and morpholino-based knockdown of vgll2a in zebrafish has been reported to cause defects in development of pharyngeal arch cartilages. However, we did not observe craniofacial anomalies in vgll2a or vgll4l homozygous mutant zebrafish nor in fish with double knockout of vgll2a and vgll4l. In Vgll2 -/- mice, which are known to present a skeletal muscle phenotype, we did not identify defects of the craniofacial skeleton. Our results suggest that although loss of VGLL2 leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development.


Voltammetric reduction of finasteride at mercury electrode and its determination in tablets.
Finasteride in hydroalcoholic solutions (ethanol/Britton-Robinson buffer, 30/70) exhibits cathodic response in a wide range of pH (-0.5 to 12) using differential pulse (DPP) and test polarography (TP). The reduction peak of finasteride at acidic pH, is a catalytic proton peak resulting from a mechanism involving a first protonation of finasteride followed by the reduction of the protons combined with finasteride in order to regenerate finasteride and liberate hydrogen. Based on the catalytic hydrogen wave, a novel method for the determination of finasteride can be proposed. For analytical purposes we selected DPP technique in an ethanol/0.0625 mol L(-1) H(2)SO(4) (30/70) solution medium. In this condition the I(p) varied linearly with finasteride concentration between 5 x 10(-5) and 5 x 10(-4) mol L(-1). Within-day and inter-day reproducibility's were adequate with R.S.D. values lower than 2%. The selectivity of the method was checked with both accelerated degradation trials and typical excipients formulations. The developed method was applied to the assay and the uniformity content of finasteride tablets and compared with the standard HPLC method. The DPP-developed method was adequate for the finasteride determination in pharmaceutical forms as that exhibited an adequate accuracy, reproducibility and selectivity. Furthermore, treatment of the sample was not required as in HPLC; the method is not time-consuming and less expensive than the HPLC ones.


Al4- cluster anion: electronic structure, excited states, and electron detachment.
Full-valence complete-active-space self-consistent-field and coupled-cluster methods are used to investigate excitation and electron detachment energies of the Al(4)(-) cluster anion. Both, Al(4) and Al(4)(-), have electronic structures with many low-energy electron configurations and exhibit accordingly pronounced configuration mixing. The complete-active-space self-consistent-field calculations show that all low-energy states of the neutral and the cluster anion can nevertheless be characterized by a single configuration, and in contrast to Møller-Plesset perturbation theory, coupled-cluster methods are found to recover enough static correlation to describe these states accurately. Coupled-cluster methods are then used to find minimal-energy structures of four states of the anion and four states of the neutral cluster, the respective ground states are identified, and vertical and adiabatic detachment energies are computed. The computed vertical detachment energies suggest that the first peak in the experimental photoelectron spectrum consists of at least three different transitions, and the computed excitation energies corroborate the conclusions from the analysis of the recently observed delayed detachment from excited Al(4)(-) ions in an electrostatic trap.


Experimental studies on Marek's disease in Japanese quail (Coturnix coturnix japonica).
Day-old quails experimentally infected with Marek's disease (MD) virus of quail origin developed lymphoid tumors. The severity of the disease increased considerably with serial passage. Tumor transplants could be made with cells derived from gross tumors in skeletal muscles, spleen cells, and blood from MD-affected quails. After five to six serial transplants, the tumor could not be transplanted further. Marek's disease tumor-associated surface antigen (MATSA) was demonstrated in lymphoid cells of spleen and peripheral blood lymphocytes of MD-affected quails. The MATSA of quail differed from the MATSA of chicken. Chickens were susceptible to MD virus isolated and propagated in quails.


Common Immunosuppressive Monotherapy for Graves' Ophthalmopathy: A Meta-Analysis.
Several immunosuppressive therapeutic regimens are widely used to treat Graves' ophthalmopathy (GO), including oral glucocorticoids (OGC), intravenous glucocorticoids (IVGC), retrobulbar injections of glucocorticoids (ROGC) and orbital radiotherapy (OR). The priority among these is unknown. This meta-analysis investigated the efficacy and tolerability of the above regimens. The PubMed, EMBASE, and Cochrane Library databases and the Chinese Biomedicine Database were searched up to November 18, 2014. Randomized controlled trials (RCTs) comparing monotherapies (OGC, IVGC, ROGC and OR) in patients with moderate-to-severe active GO were selected. The main efficacy measures were the response rate, the standard mean difference (SMD) in the reduction in the clinical activity score (CAS) and the mean difference (MD) in proptosis from baseline to the end of treatment. The main tolerability measure was the risk ratio (RR) for adverse events. The pooled estimates and 95% confidence intervals (95% CIs) were calculated using the RevMan software, version 5.1. Seven published RCTs involving 328 participants were included in the present meta-analysis, including IVGC versus OGC (3 trials), ROGC versus OGC (3 trials) and OR versus OGC (1 trial). IVGC was more effective than OGC in response rate (RR = 1.48, 95% CI = 1.18-1.87) and had an obvious CAS reduction (SMD = 0.69, 95% CI = 0.13-1.25). IVGC caused fewer adverse events than OGC. ROGC and OGC had no statistically significant difference in response rate (RR = 1.16, 95% CI = 0.94-1.42). OR also did not differ significantly compared with OGC (RR = 0.93, 95% CI = 0.54-1.60). ROGC and OR had fewer adverse events, such as weight gain, compared with OGC. For patients with GO in the moderate-to-severe active phase, current evidence gave priority to IVGC, which had a statistically significant advantage over OGC and caused fewer adverse events. ROGC and OR did not provide greater efficacy than OGC, although better tolerability and fewer adverse events were shown.


A comparison of the clinical characteristics of intermittent exotropia in children and adults.
The purpose of this study was to compare and differentiate the clinical characteristics of intermittent exotropia (X(T)) in children and adults. This study included 398 patients with X(T): 360 children ranging in age from 1 to 14 years and 38 adults over 15 years of age. Patients with neurological abnormalities or developmental delays were excluded. Clinical characteristics of interest included sex, age on first visit, age of onset, type of onset, duration to surgery, family history, chief complaints, type of fixation, refractive errors, sensory tests, angle of deviation, fundus examination, oblique muscle dysfunction, and other associated ocular disorders. In both groups, an insidious onset was more common than a sudden onset (p=0.033). Outward deviation was the most common chief complaint in both groups, followed by photophobia in the childhood group, and diplopia in the adult group. The most common subtype of X(T) was the basic type. The mean near deviation was 23.6+/-7.9 prism diopters (PD) in the childhood group and 30.7+/-12.2 PD in the adult group (p=0.01). The mean distance deviation was 23.4+/-6.1 PD and 28.3+/-11.2 PD in the childhood and adult groups, respectively (p=0.028). The rate of fusion, measured with the Worth 4-dot test at near and distance was higher in the childhood group, as compared to the adult group (p=0.024 and p=0.048, respectively). Among X(T) patients, the chief complaints, angle of deviation, and Worth 4-dot tests showed significant differences between the childhood and adult groups. Therefore, these are important factors to consider when assessing adults and children with X(T).


Regional localisation of a non-specific X-linked mental retardation gene (MRX19) to Xp22.
A gene responsible for a non-specific form of X-linked mental retardation (MRX19) was localised by linkage analysis. Exclusions and regional localisation were made using 21 highly informative PCR-based markers along the X chromosome. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS207, DXS987 (Zmax = 3.58) and DXS999 (Zmax = 3.28) indicating that this gene is localised to the proximal portion of Xp22. Recombination between MRX19 and the flanking loci KAL and DXS989 was observed. The multipoint CEPH background map, with map distances in cM, is DXS996-1.8-KAL-19.0-DXS207-0.9-[DXS987,DXS443 ]-4.3-DXS999-3.5-DXS365-14.0-DXS989. Two other MRX disorders and two syndromal mental retardations, Coffin-Lowry syndrome and Partington syndrome, have been mapped to this region. There is a possibility that the 3 MRX disorders are the same entity. Most MRX disorders remain clustered around the pericentromeric region.


Expression of prostaglandin endoperoxide H synthase 1 and 2 in human placenta at term.
Prostaglandins play an important role in reproduction, particularly in pregnancy and parturition. We investigated the expression of prostaglandin endoperoxide H synthase (PGHS) 1 and 2, key enzymes in prostaglandin biosynthesis, in the human placenta at term. Northern blot analysis of placenta total and poly(A)+ RNA failed to detect significant levels of PGHS-1 mRNA, using a human PGHS-1 specific DNA probe. In contrast, definite PGHS-2 mRNA bands, with a calculated size of about 4.5 kb, were observed in Northern blots of placenta poly(A)+ RNA, using a PGHS-2 specific DNA probe. Moreover, PGHS-1 and PGHS-2 expression was assessed at the translational level by Western blot analysis. Thus, using three highly specific antibodies, we found a selective expression of PGHS-2 immunoreactive protein. These results indicate that PGHS-2 is the PGHS isoform prevalently expressed in the human placenta at term and support the hypothesis that PGHS-2 plays a prominent role in the maintenance of pregnancy, in line with the proposed anti-apoptotic and growth promoting properties of this enzyme.


Distinct Cleavage Properties of Cathepsin B Compared to Cysteine Cathepsins Enable the Design and Validation of a Specific Substrate for Cathepsin B over a Broad pH Range.
The biological and pathological functions of cathepsin B occur in acidic lysosomes and at the neutral pH of cytosol, nuclei, and extracellular locations. Importantly, cathepsin B displays different substrate cleavage properties at acidic pH compared to neutral pH conditions. It is, therefore, desirable to develop specific substrates for cathepsin B that measure its activity over broad pH ranges. Current substrates used to monitor cathepsin B activity consist of Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, but they lack specificity since they are cleaved by other cysteine cathepsins. Furthermore, Z-Arg-Arg-AMC monitors cathepsin B activity at neutral pH and displays minimal activity at acidic pH. Therefore, the purpose of this study was to design and validate specific fluorogenic peptide substrates that can monitor cathepsin B activity over a broad pH range from acidic to neutral pH conditions. In-depth cleavage properties of cathepsin B were compared to those of the cysteine cathepsins K, L, S, V, and X via multiplex substrate profiling by mass spectrometry at pH 4.6 and pH 7.2. Analysis of the cleavage preferences predicted the tripeptide Z-Nle-Lys-Arg-AMC as a preferred substrate for cathepsin B. Significantly, Z-Nle-Lys-Arg-AMC displayed the advantageous properties of measuring high cathepsin B specific activity over acidic to neutral pHs and was specifically cleaved by cathepsin B over the other cysteine cathepsins. Z-Nle-Lys-Arg-AMC specifically monitored cathepsin B activity in neuronal and glial cells which were consistent with relative abundances of cathepsin B protein. These findings validate Z-Nle-Lys-Arg-AMC as a novel substrate that specifically monitors cathepsin B activity over a broad pH range.


Alertness-based subject-dependent and subject-independent filter optimization for improving classification efficiency of SSVEP detection.
Mental task-based brain computer interface (BCI) systems are usually developed for neural prostheses technologies and medical rehabilitation. The mental workload was too heavy for the user to manipulate BCI effectively. Fortunately, electroencephalography (EEG) signal is not only used for BCI control but also relates to the changes of mental states. We proposed a novel method for identifying non-effective trials of Steady State Visual Evoked Potential (SSVEP)-based BCI. We used the subject-dependent and subject-independent alertness models identifying non-effective trials of SSVEP-BCI systems. The result implied that the subject-dependent alertness model was most useful for improving the classification accuracy in the task. However, the subject-independent alertness model could enhance the prediction ability of SSVEP-based BCI system. In comparison to the conventional canonical correlation analysis (CCA) method without alertness-model filtering, the raise of precision was valuable for the technical development of BCI works. It demonstrated the effectiveness of our proposed subject-dependent and subject-independent methods.


Enhanced Osseointegration of Porous Titanium Modified with Zeolitic Imidazolate Framework-8.
Nanoscale zeolitic imidazolate framework-8 (ZIF-8)-modified titanium (ZIF-8@AHT) can enhance osteogenesis in vitro. In this study, we systematically and quantitatively examined the effects of ZIF-8@AHT on osteogenesis, and investigated its ability to form bone in vivo. First, we coated various quantities of nanoscale ZIF-8 crystals on alkali- and heat-treated titanium (AHT) by controlling the concentration of the synthesis solution. We then characterized the ZIF-8@AHT materials using scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and determination of the sessile drop contact angle. To illustrate the combined effects of micro/nanotopography and ZIF-8@AHT composition on bone regeneration, we cultured MC3T3-E1 preosteoblast cells on various titanium substrates in vitro by setting pure titanium (Ti) and AHT as control groups. The ZIF-8@AHTs enhanced cell bioactivity compared with AHT and Ti, as evidenced by increased extracellular matrix (ECM) mineralization, collagen secretion and the upregulated expression of osteogenic genes (Alp, Col1, Opg, and Runx2) and osteogenesis-related proteins (ALP and OPG). ZIF-8@AHT-1/8 exhibited better osteogenic activity compared with the other ZIF-8@AHT groups investigated. We subsequently inserted Ti, AHT, and ZIF-8@AHT-1/8 implants into the healed first molars (M1s) of mice, and found that ZIF-8@AHT-1/8 also promoted osseointegration at the bone-implant interface. These results suggest that ZIF-8@AHT-1/8 has great potential for practical application in implant modification.


Analogue and digital electrocardiogram recordings in the assessment of heart rate variability.
We compared analogue and digital 24-h electrocardiogram (ECG) recordings in the assessment of heart rate variability (HRV) in 41 patients with suspected coronary artery disease. The patients underwent ambulatory ECG recordings simultaneously with analogue (A) (Marquette 8500) and digital (D) (Oxford Medilog FD-3) recorders. Digital ECG recordings were analysed with the Excel Medilog II system (DE) and analogue recordings were analysed with both Marquette (AM) and Excel Medilog II (AE) systems. SDNN, SDANN, rMSSD and pNN50 were calculated for the assessment of time domain measures of HRV, and powers of low (0.04-0.15 Hz) and high (0.15-0.40 Hz) spectral components of HRV for the assessment of frequency domain measures of HRV. Correlations between time domain measures of HRV derived from AM, AE and DE recording and analysis techniques were high (r = 0.803-0.999, P < 0.001). SDANN and pNN50 assessed with AM and DE were equal, whereas SDNN and rMSSD values differed slightly but significantly from each other (P < 0.01 for both). All time domain measures of HRV assessed with AE differed significantly from AM (P < 0.001) and from DE (P < 0.01). Correlations between frequency domain measures of HRV derived from AM, AE and DE were also high (r = 0.973-0.992, P < 0.001). Despite this, frequency domain measures of HRV assessed with AM, AE and DE differed significantly from each other (P < 0.001). In conclusion, when analysed with their own analysis systems, analogue and digital recordings provided almost identical time domain, but not frequency domain, measures of HRV. In addition, analysis of an ECG recording with an analysis system of different manufacturer should be avoided.


Delayed but successful response to noninvasive ventilation in COPD patients with acute hypercapnic respiratory failure.
We evaluated a new noninvasive ventilation (NIV) protocol that allows the pursuit of NIV in the case of persistent severe respiratory acidosis despite a first NIV challenge in COPD patients with acute hypercapnic respiratory failure (AHRF). A prospective observational multicentric pilot study was conducted in three tertiary hospitals over a 12-month study period. A total of 155 consecutive COPD patients who were admitted for AHRF and treated by NIV were enrolled. Delayed response to NIV was defined as a significant clinical improvement in the first 48 h following NIV initiation despite a persistent severe respiratory acidosis (pH <7.30) after the first 2 h of NIV trial. NIV failed in only 10 patients (6.5%). Delayed responders to NIV (n=83, 53%) exhibited similar nutritional status, comorbidities, functional status, frailty score, dyspnea score, and severity score at admission, compared with early responders (n=62, 40%). Only age (66 vs 70 years in early responders; P=0.03) and encephalopathy score (3 [2-4] vs 3 [2-4] in early responders; P=0.015) were different among the responders. Inhospital mortality did not differ between responders to NIV (n=10, 12% for delayed responders vs n=10, 16% for early responders, P=0.49). A second episode of AHRF occurred in 20 responders (14%), equally distributed among early and delayed responders to NIV (n=9, 14.5% in early responders vs n=11, 13% in delayed responders; P=0.83), with a poor survival rate (n=1, 5%). Most of the COPD patients with AHRF have a successful outcome when NIV is pursued despite a persistent severe respiratory acidosis after the first NIV trial. The outcome of delayed responders is similar to the one of the early responders. On the contrary, the second episode of AHRF during the hospital stay carries a poor prognosis.


Highly active self-immobilized FI-Zr catalysts in a PCP framework for ethylene polymerization.
A series of zirconium-based porous coordination polymers (PCPs) containing FI catalysts in the frameworks have been developed and studied as catalysts for ethylene polymerization. These PCPs exhibit good catalytic activities and long life times, producing polyethylenes with high molecular weights and bimodal molecular weight distribution in the form of particles.


STIM1 positively regulates the Ca2+ release activity of the inositol 1,4,5-trisphosphate receptor in bovine aortic endothelial cells.
The endothelium is actively involved in many functions of the cardiovascular system, such as the modulation of arterial pressure and the maintenance of blood flow. These functions require a great versatility of the intracellular Ca2+ signaling that resides in the fact that different signals can be encoded by varying the frequency and the amplitude of the Ca2+ response. Cells use both extracellular and intracellular Ca2+ pools to modulate the intracellular Ca2+ concentration. In non-excitable cells, the inositol 1,4,5-trisphosphate receptor (IP3R), located on the endoplasmic reticulum (ER), is responsible for the release of Ca2+ from the intracellular store. The proteins STIM1 and STIM2 are also located on the ER and they are involved in the activation of a store-operated Ca2+ entry (SOCE). Due to their Ca2+ sensor property and their close proximity with IP3Rs on the ER, STIMs could modulate the activity of IP3R. In this study, we showed that STIM1 and STIM2 are expressed in bovine aortic endothelial cells and they both interact with IP3R. While STIM2 appears to play a minor role, STIM1 plays an important role in the regulation of agonist-induced Ca2+ mobilization in BAECs by a positive effect on both the SOCE and the IP3R-dependent Ca2+ release.


Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis.
Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.


Boiling Transitions During Droplet Contact on Superheated Nano/Micro-Structured Surfaces.
Manipulating surface topography is one of the most promising strategies for increasing the efficiency of numerous industrial processes involving droplet contact with superheated surfaces. In such scenarios, the droplets may immediately boil upon contact, splash and boil, or could levitate on their own vapor in the Leidenfrost state. In this work, we report the outcomes of water droplets coming in gentle contact with designed nano/microtextured surfaces at a wide range of temperatures as observed using high-speed optical and X-ray imaging. We report a paradoxical increase in the Leidenfrost temperature (TLFP) as the texture spacing is reduced below a critical value (∼10 μm) that represents a minima in TLFP. Although droplets on such textured solids appear to boil upon contact, our studies suggest that their behavior is dominated by hydrodynamic instabilities implying that the increase in TLFP may not necessarily lead to enhanced heat transfer. On such surfaces, the droplets display a new regime characterized by splashing accompanied by a vapor jet penetrating through the droplets before they transition to the Leidenfrost state. We provide a comprehensive map of boiling behavior of droplets over a wide range of texture spacings that may have significant implications toward applications such as electronics cooling, spray cooling, nuclear reactor safety, and containment of fire calamities.


Depression Predicts Prolonged Length of Hospital Stay in Pediatric Inflammatory Bowel Disease.
Few studies report the impact of depression on inflammatory bowel disease (IBD)-related hospitalizations. We evaluated the association between depression and pediatric IBD-related hospitalizations. Our primary aim was to test the hypothesis that depression is associated with hospital length of stay (LOS); our secondary goal was to evaluate if patients with depression are at higher risk for undergoing additional imaging and procedures. Data were extracted from the 2012 Kids Inpatient Database (KID), the largest nationally representative publicly available all-payer pediatric inpatient cross-sectional database in the United States. Hospitalizations for patients less than 21 years with a primary diagnosis Crohn disease (CD) or ulcerative colitis (UC) by ICD-9 code were included. Multivariable logistic regression was used to predict long LOS controlling for patient- and hospital-level variables and for potential disease confounders. For primary IBD-related hospitalizations (N = 8222), depression was associated with prolonged LOS (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.19-1.90) and total parenteral nutrition use (OR 1.54; 95% CI 1.04-2.27). Depression was not associated with increased likelihood of surgery (OR 0.97; 95% CI 0.72-1.30), endoscopy (OR 0.91; 95% CI 0.74-1.14), blood transfusion (OR 0.85; 95% CI 0.58-1.23), or abdominal imaging (OR 1.15; 95% CI 0.53-2.53). Depression is associated with prolonged LOS in pediatric patients with IBD, even when controlling for gastrointestinal disease severity. Future research evaluating the efficacy of standardized depression screening and early intervention may be beneficial to improving inpatient outcomes in this population.


Inflammation and apoptosis.
Apoptosis is a highly regulated form of programmed cell death defined by distinct morphological and biochemical features; it plays an important role in embryogenesis and the maintenance of cellular and tissue homeostasis in multicellular organisms. Its perturbation has been implicated in a wide range of patho-physiological stages, including autoimmune, bacterial, and viral disease, and degenerative disorders. The critical role of apoptosis in eliminating harmful or injured cells from tissues suggests its participation in inflammatory processes and in the resolution of inflammatory reactions. In this article, we briefly review the molecular mechanism of apoptosis and the role of apoptosis in inflammation.


Haemolytic activity of copper as influenced by chelating agents, albumine and chromium.
The haemolytic activity of CuSO4 (0.3 mM) in vitro was reduced in the presence of albumine (5-20 g/l). The presence of D-penicillamine, triethylene tetramine or dimercaptosuccinic acid (0.3 mM) also reduced the copper-induced haemolysis, whereas 2,3-dimercaptopropane-1-sulphonate increased the cytolysis. N-ethylmaleimide (NEM) in appropriate concentrations (1 mM), as well as chromic chloride (0.3 mM), reduced the copper-induced haemolysis. Higher concentrations of NEM (2 mM) were ineffective. The results may provide helpful suggestions as regarding the clinical treatment of copper poisoning and Wilson's disease. The results may also be helpful for the understanding of the mechanisms of haemolysis associated with copper intoxication in vivo.


Psychological characteristics of dissatisfied denture patients.
A field study was conducted to investigate the psychological characteristics of dissatisfied denture patients using validated personality inventories. In the present study dissatisfied denture patients are patients that keep complaining about their dentures and are referred to a psychologist because it was suspected that their complaints may also be due to psychological factors. The results show that these patients feel more inhibited in their social contacts and more often have the opinion that wearing dentures is unacceptable. Also these patients are high on neuroticism, less social adequate, more rigid, have less self-esteem and are more externally oriented.


Isolated posterior capsular rupture following blunt head trauma.
Closed-globe traumatic cataract is not uncommon in males in the pediatric age group. However, there is a relative paucity of literature on isolated posterior lens capsule rupture associated with closed-globe traumatic cataract. We report a case of a 6-year-old boy who presented with white cataract 1 day after blunt trauma to the forehead associated with posterior capsular rupture that was detected by B-scan ultrasonography preoperatively. No stigmata of trauma outside the posterior capsule could be detected by slit-lamp exam, funduscopy, and optical coherence tomography. Phacoemulsification with posterior chamber intraocular lens implant was performed 24 hours after trauma, with the patient achieving 6/6 visual acuity 1 week and 6 months after surgery. Our case is unique, being the youngest (amblyogenic age) to be reported, with prompt surgical intervention, and with no signs of trauma outside the posterior capsule.


Postharvest physio-pathological disorders in table grapes as affected by UV-C light.
To gain knowledge on the influence of postharvest treatments with ultraviolet-C light upon the keeping quality of table grapes, a trail was performed employing commercially mature 'Corina', 'Dawn Seedless', 'Centennial Seedless' and 'Gran Perlon' grape cultivars (cvs). After grading, bunches were subjected to 0.0, 0.5, 1.5 or 3 kJm(-2) and then stored at 5 degrees C and 90% relative humidity (RH) for 6 weeks followed by a 2 day shelf-life at 25 degrees C and 70% RH. A weekly inspection was performed and a visual evaluation of the appearance, treatment damage, stems browning and berry shrivelling was performed. Weight loss, decay and shatter were quantified at the end of storage and shelf-life. Regardless the cv and UV-C dose, fruit appearance was acceptable until the end of storage and shelf-life. Among the cvs, the highest score was held by 'G. Perlon'. After the fourth week of storage, the berries of 'Centennial S.' turned light brown and darkened over time when treated with 3.0 kJm(-2). Stem browning was not induced by the light treatment, but resulted cv depended and was pronounced for 'Centennial S.' and 'Dawn S.'. Berry shrivelling was insignificant, while shatter was very high in 'Corina' and did not depend upon UV-C treatment. Regarding weight loss, differences could not be attributed to the light treatment and after storage it ranged from 3 up to 5%. Decay was significantly reduced by light treatment and the efficacy increased by raising the dose. Botrytis cinerea was the main cause of decay with 'Corina' being the most jeopardized, followed by 'Dawn S.' and 'Centennial S.', whereas 'G. Perlon' resulted the less affected. In conclusion, hormetic effects of postharvest light treatment on table grapes were observed in almost all cvs with 'G. Perlon' having the best performance.


[KYOTO CONSENSUS - THE NEW ETIOLOGICAL CLASSIFICATION OF CHRONIC GASTRITIS AND ITS DISCUSSION].
The main provisions and headings of the new etiological classification of chronic gastritis are discussed in the context of recent data on the true role of Helicobacter pylori infection in the development of this pathology. The methods and results of the authors ' investigations into gastric microflora are presented along with information about the frequency of detection of its different forms, concentration of microbial forms in gastric mucosa, their pathogenic properties including urease activity, and possible contribution to chronic gastritis etiology. The possibility of alcoholic and chemical chronic gastritis is discussed along with the role of these conditions in the development of stomach cancer. Special emphasis is laid on the disagreement between the adopted consensuses and principles of evidence-based medicine.


[Analysis of the articles published in Chinese Journal of Applied Physiology between 2000 and 2006].
To analyze the characteristics of publications of Chinese Journal of Applied Physiology between 2000 and 2006, evaluate the academic level and the popularity of the issues, and supplying an evidence for the journal reform. With CNKI and manpower search, by use of literature metrology, a comprehensive analysis of the publications of Chinese Journal of Applied Physiology between 2000 and 2006 was made. The number of articles published form 2000 to 2006 in Chinese Journal of Applied Physiology was 968, The average number of each issue is 34.57, the average page of each article is 3.11, in the columns, the article about original articles was top of rank (66.22% of the total). In the quotation, the quotation increase year by year (100% in 2004-2006), the number of English quotation is very more (76.52% in average). In the time lag, the longest is 510 days, the shortest if 60 days, the average is 196.51 days. In the fund support, the level is increase by fund support, the article number by fund support is increase too, It is 97 in 2005. In the authors' professional positions and academic degrees, the authors' level is more and more higher. In the authors column, Beijing's author is the top of rank, has 162 persons (16.74% of the total). The Chinese Journal of Applied Physiology has published high quality articles. It is the one of the most important information resource for the physiological research and the most important medical journal.


Effects of low-frequency biasing on spontaneous otoacoustic emissions: frequency modulation.
It was previously reported that low-frequency biasing of cochlear structures can suppress and modulate the amplitudes of spontaneous otoacoustic emissions (SOAEs) in humans [Bian, L. and Watts, K. L. (2008). "Effects of low-frequency biasing on spontaneous otoacoustic emissions: Amplitude modulation," J. Acoust. Soc. Am. 123, 887-898]. In addition to amplitude modulation, the bias tone produced an upward shift of the SOAE frequency and a frequency modulation. These frequency effects usually occurred prior to significant modifications of SOAE amplitudes and were dependent on the relative strength of the bias tone and a particular SOAE. The overall SOAE frequency shifts were usually less than 2%. A quasistatic modulation pattern showed that biasing in either positive or negative pressure direction increased SOAE frequency. The instantaneous SOAE frequency revealed a "W-shaped" modulation pattern within one biasing cycle. The SOAE frequency was maximal at the biasing extremes and minimized at the zero crossings of the bias tone. The temporal modulation of SOAE frequency occurred with a short delay. These static and dynamic effects indicate that modifications of the mechanical properties of the cochlear transducer could underlie the frequency shift and modulation. These biasing effects are consistent with the suppression and modulation of SOAE amplitude due to shifting of the cochlear transducer operating point.


The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine.
Clozapine is a unique antipsychotic, with efficacy against positive symptoms in treatment-resistant schizophrenic patients, and the ability to improve cognition and treat the negative symptoms characteristic of this disease. Despite its unique clinical actions, no specific molecular mechanism responsible for these actions has yet been described. To comprehensively profile a large library of neuropsychiatric drugs, including most antipsychotics, at human monoamine receptors using R-SAT, an in vitro functional assay. Profiling revealed that N-desmethylclozapine (NDMC), the principal metabolite of clozapine, but not clozapine itself, is a potent and efficacious muscarinic receptor agonist, a molecular property not shared by any other antipsychotic. To further explore the role of NDMC muscarinic receptor agonist properties in mediating the physiological actions of clozapine, systemically administered NDMC was found to stimulate the phosphorylation of mitogen-activated protein kinase (MAP kinase) in mouse CA1 hippocampal neurons, an effect that was blocked by scopolamine, confirming central M1 muscarinic receptor agonist activity in vivo. Lastly, an analysis of clozapine and NDMC serum levels in schizophrenic patients indicated that high NDMC/clozapine ratios better predicted improvement in cognitive functioning and quality of life than the levels of either compound alone. The muscarinic receptor agonist activities of NDMC are unique among antipsychotics, and provide a possible molecular basis for the superior clinical effects of clozapine pharmacotherapy.


Epidermal growth factor receptor abnormalities in atypical teratoid/rhabdoid tumors and an unusual case with gene amplification.
Atypical teratoid/rhabdoid tumor (AT/RT) is a rhabdoid tumor of the central nervous system comprising a mixture of small round cells and mesenchymal and/or epithelial elements, showing mutation of the SMARCB1 gene or SMARCA4 gene. The epidermal growth factor receptor (EGFR) is one of the tyrosine kinase receptors whose overexpressed protein plays important roles in the malignant characteristics of various tumors. We analyzed 8 Japanese cases of AT/RT for EGFR protein overexpression and egfr gene amplification using immunohistochemistry and fluorescence in situ hybridization. The patients included 7 boys and 1 girl (age range 13 days to 2 years), and the tumors were localized in the frontal lobe (1 case), lateral ventricle (1 case), third ventricle (1 case), fourth ventricle (3 cases), and cerebellum (2 cases). We found that all (100%) of them partially expressed a high level of EGFR protein, and that one case showed amplification of egfr, the amplified area being localized and limited to a specific area within the tumor. We speculate that AT/RT is a tumor with heterogeneous egfr amplification, and that the frequency of amplification may depend on loss of function of the specific chromatin-remodeling member.


[Anesthetic management of parturients with intracranial hemorrhage accompanied by seizure].
Two preeclamptic parturients, who presented with generalized seizure, underwent emergency cesarean section without confirmed diagnosis. They developed focal neurological signs postoperatively, and were subsequently diagnosed as subarachnoid hemorrhage due to rupture of an intracranial aneurysm and possibly of arteriovenous malformation. Diagnosis should be made at the earliest possible time for the optimal anesthetic as well as postoperative management of the mother.


Surface Chemistry of Nanoscale Mineralized Collagen Regulates Periodontal Ligament Stem Cell Fate.
The interplay between stem cells and their extracellular microenvironment is of critical importance to the stem cell-based therapeutics in regenerative medicine. Mineralized collagen is the main component of bone extracellular matrix, but the effect of interfacial properties of mineralized collagen on subsequent cellular behaviors is unclear. This study examined the role of surface chemistry of nanoscale mineralized collagen on human periodontal ligament stem cell (hPDLSC) fate decisions. The intrafibrillarly mineralized collagen (IMC), fabricated by a biomimetic bottom-up approach, showed a bonelike hierarchy with nanohydroxyapatites (HAs) periodically embedded within fibrils. The infrared spectrum of the IMC showed the presence of phosphate, carbonate, amide I and II bands; and infrared mapping displayed uniform and higher spatial distribution of mineralization in the IMC. However, the distribution of the phosphate group differed far from that of the amide I group in the extrafibrillarly mineralized collagen (EMC), in which flowerlike HA clusters randomly depositing around the surface of the fibrils. Moreover, a large quantity of extrafibrillar HAs covered up the C═O stretch and N-H in-plane bend, resulting in substantial reduction of amide I and II bands. Cell experiments demonstrated that the hPDLSCs seeded on the IMC exhibited a highly branched, osteoblast-like polygonal shape with extended pseudopodia and thick stress fiber formation; while cells on the EMC displayed a spindle shape with less branch points and thin actin fibril formation. Furthermore, the biocompatibility of EMC was much lower than that of IMC. Interestingly, even without osteogenic induction, mRNA levels of major osteogenic differentiation genes were highly expressed in the IMC during cultivation time. These data suggest that the IMC with a similar nanotopography and surface chemistry to natural mineralized collagen directs hPDLSCs toward osteoblast differentiation, providing a promising scaffold in bone tissue regeneration.


Bone and Soft Tissue Modifications in Immediate Implants Versus Delayed Implants Inserted Following Alveolar Ridge Preservation: A Randomized Controlled Clinical Trial. Part I: Esthetic Outcomes.
Soft tissue changes were evaluated over a period of 1 year in 48 patients who required extraction of a single tooth in the anterior maxillary arch (premolar to premolar) and its replacement with an implant. The patients were randomly divided into two groups: In group A, an immediate postextraction implant was placed, and the bone-to-implant gap was filled with bovine bone mineral; in group B, the alveolar ridge preservation technique was performed after extraction, and the implant was placed 4 months later. On the day of tooth extraction (T0) and 1 year after tooth extraction (T1), the soft tissue horizontal width, mesial and distal papillary levels, midfacial gingival level, and Pink Esthetic Score were evaluated in both groups. No significant differences were observed between the groups in any of the considered parameters. Statistically significant differences were found in the soft tissue horizontal width between T0 and T1. The clinical results of the two procedures were similar and comparable over time. When evaluating the stability of the soft tissue contour, and considering the specific indications of the two techniques, it is possible to choose either an immediate implant or an alveolar ridge preservation technique with staged placement.


[Stimulation Program Health Research. XI. Evaluation of the section 'Rehabilitation Medicine'].
As a part of the SGO Health Research Promotion Programme a research programme on rehabilitation medicine was realized. Aim of the programme was to strengthen clinical research in this field by training clinical researchers and improving clinical research infrastructure. Three clinical specialists have been trained to become senior clinical researchers by a 4-year training programme, concentrated within 2 clusters of a medical faculty, a university hospital and one or more centres for rehabilitation medicine. As a follow-up to the programme a 6-week educational course was developed for intending MDs in rehabilitation medicine and five intending rehabilitation medicine specialists receive a PhD research training during their clinical specialisation.


Antibody polyreactivity in health and disease: statu variabilis.
An Ab molecule or a BCR that is able to bind multiple structurally unrelated Ags is defined as polyreactive. Polyreactive Abs and BCRs constitute an important part of immune repertoires under physiological conditions and may play essential roles in immune defense and in the maintenance of immune homeostasis. In this review, we integrate and discuss different findings that reveal the indispensable role of Ag-binding polyreactivity in the immune system. First, we describe the functional and molecular characteristics of polyreactive Abs. The following part of the review concentrates on the biological roles attributed to polyreactive Abs and to polyreactive BCRs. Finally, we discuss recent studies that link Ig polyreactivity with distinct pathological conditions.


Automation in quantifying phenoxy herbicides and bentazon in surface water and groundwater using novel solid phase extraction and liquid chromatography tandem mass spectrometry.
The occurrence of phenoxy herbicides is a financial and regulatory concern for drinking water treatment plants. This paper presents a new method of quantification for nine phenoxy-acids and bentazon in different water samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). The method is based on an automated solid phase extraction (SPE) process that applied hydrophilic modified polystyrene and divinylbenzene cartridges at low pH (<2.0). Main advantages of the presented method include the reduced consumption of organic solvent in extraction and the fully automated sample pre-concentration. The method is thus more environmentally-friendly. In the quantification step, five stable isotopically labelled analogues were used as internal standards to account for the losses during sample preparation and to calibrate the ion source response under the mass spectrometric detection. The method was optimized in terms of sample preparation and subsequent LC-MS/MS separation to obtain reliable measurement of the analyte concentration during real sample analysis. The method quantification limit was between 1.5 and 10.0 ng/L for target compounds in surface water and groundwater samples. The method was validated at three fortification levels between 10.0 and 1000 ng/L, and the results showed fit-for-purpose recovery with appropriate precision at low concentration levels. The method was also utilized to analyse thirty-two actual water samples from different sources. Forty percent of the analysed samples contained detectable level of herbicides, ranging from 1.91 to 40.5 ng/L. The concentrations of targeted herbicides in our study were comparable to those found in water samples in other regions of world.


Functional comparison of the two gene products of Thogoto virus segment 6.
The sixth genomic segment of Thogoto virus (THOV) encodes two proteins, the viral matrix protein (M) and an accessory protein with an interferon (IFN)-antagonistic function named ML. M and ML are shown in this study to be structural components of the virion. Using an in vivo system based on the reconstitution of functional THOV ribonucleoprotein complexes from cloned cDNAs, it was demonstrated that M has an inhibitory effect on the viral RNA-dependent RNA polymerase (RdRP) and is essential for the formation of virus-like particles (VLPs). The functional domain responsible for the regulation of RdRP activity resides within the C-terminal half of M, while full-length M protein is required for VLP formation. The ML protein cannot complement M with respect to either RdRP downregulation or particle formation, although it is identical to M apart from a 38 aa extension at the C terminus. In contrast, ML, but not M, is able to prevent the induction of IFN-beta by double-stranded RNA. This function is contained within the C-terminal half of ML. These data suggest major structural differences between M and ML that could explain the different activities of the two proteins.


Text message reminders for timely routine MMR vaccination: A randomized controlled trial.
Measles-mumps-rubella (MMR) vaccination is important for preventing disease outbreaks, yet pockets of under-vaccination persist. Text message reminders have been employed successfully for other pediatric vaccines, but studies examining their use for MMR vaccination are limited. This study assessed the impact of text message reminders on timely MMR vaccination. Parents (n=2054) of 9.5-10.5-month-old children from four urban academically-affiliated pediatric clinics were randomized to scheduling plus appointment text message reminders, appointment text message reminder-only, or usual care. The former included up to three text reminders to schedule the one-year preventive care visit. Both text messaging arms included a text reminder sent 2 days before that visit. Outcomes included appointment scheduling, appointment attendance, and MMR vaccination by age 13 months, the standard of care at study sites. Children of parents in the scheduling plus appointment text message reminders arm were more likely to have a scheduled one-year visit than those in the other arms (71.9% vs. 67.4%, relative risk ratio (RRR) 1.07 [95% CI 1.005-1.13]), particularly if no appointment was scheduled before randomization (i.e., no baseline appointment) (62.1% vs. 54.7%, RRR 1.14 [95% CI 1.04-1.24]). One-year visit attendance and timely MMR vaccination were similar between arms. However, among children without a baseline appointment, those with parents in the scheduling plus appointment text message reminders arm were more likely to undergo timely MMR vaccination (61.1% vs. 55.1%, RRR 1.11 [95% CI 1.01-1.21]). Text message reminders improved timely MMR vaccination of high-risk children without a baseline one-year visit.


Update on angiogenesis inhibitors.
A number of therapeutic agents have been developed which have anti-angiogenic potential. Here we present the most recent data from clinical trials with some of the promising inhibitors of angiogenesis. Agents that target the vascular endothelial growth factor signaling pathway are the furthest along in clinical development. The last year has brought US Food and Drug Administration approval of bevacizumab (Avastin), a recombinant humanized anti-vascular endothelial growth factor monoclonal antibody. Bevacizumab has demonstrated a survival advantage in combination with chemotherapy for patients with metastatic colorectal cancer. Other agents with early promising results include PTK787/ZK 222584 (Vatalanib), ZD6474, and BAY 43-9006 (Sorafenib). Angiogenesis inhibitors show promise, but evaluation for optimal efficacy has been a problem, given that the mechanisms of action of these agents differ from conventional cytotoxic agents and surrogate markers for inhibition of angiogenesis are not available.


A photo-essay of the life and times of Herbert Remmer with his friends.
There are many wonderful memories one can relate about Herbert Remmer. He was a dedicated scientist, an excellent colleague, and a distinctive character in the international field of drug metabolism and toxicology. This article describes my first meeting in 1964 with Herbert Remmer. The article highlights his seminal contributions to our understanding of cytochrome P450 induction and the associated changes in the morphological contributions of the endoplasmic reticulum of the liver and the role of P450 as it relates to drug interactions as the initial step in drug metabolism. Also described are results of experiments carried out in 1964 when Herbert Remmer visited our laboratory at the Johnson Foundation of the University of Pennsylvania. It was these spectrophotometric experiments, showing spectral changes associated with the binding of drugs to liver microsomal P450 (with John Schenkman), that laid the foundation for our current understanding of the cyclic mechanism of P450 function during the metabolism of a great variety of xenobiotics. Herbert Remmer will be remembered as a frequent actor on the world stage of science. This article includes some of the many pictures I have in my files of Herbert Remmer and his friends as we traveled to exotic venues for scientific discussions of drug metabolism, toxicology, and risk assessment.


Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.
The platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. Although cisplatin shows a broad spectrum of anticancer activity, its utility is limited due to acquired drug resistance and toxicity to non-targeted tissues. Here, by integrating genome-wide high-throughput Damage-seq, XR-seq, and RNA-seq approaches, along with publicly available epigenomic data, we systematically study the genome-wide profiles of cisplatin damage formation and excision repair in mouse kidney, liver, lung and spleen. We find different DNA damage and repair spectra across mouse organs, which are associated with tissue-specific transcriptomic and epigenomic profiles. The framework and the multi-omics data we present here constitute an unbiased foundation for understanding the mechanisms of cellular response to cisplatin. Our approach should be applicable for studying drug resistance and for tailoring cancer chemotherapy regimens.


Inhibition of type I interferon induction and signalling by mosquito-borne flaviviruses.
The Flavivirus genus (Flaviviridae family) contains a number of important human pathogens, including dengue and Zika viruses, which have the potential to cause severe disease. In order to efficiently establish a productive infection in mammalian cells, flaviviruses have developed key strategies to counteract host immune defences, including the type I interferon response. They employ different mechanisms to control interferon signal transduction and effector pathways, and key research generated over the past couple of decades has uncovered new insights into their abilities to actively decrease interferon antiviral activity. Given the lack of antivirals or prophylactic treatments for many flaviviral infections, it is important to fully understand how these viruses affect cellular processes to influence pathogenesis and disease outcome. This review will discuss the strategies mosquito-borne flaviviruses have evolved to antagonise type I interferon mediated immune responses.


Two Gingival Cell Lines Response to Different Dental Implant Abutment Materials: An In Vitro Study.
Objectives: This study aimed to investigate the response of human gingival fibroblasts (HGFB) and human gingival keratinocytes (HGKC) towards different dental implant abutment materials. Methods: Five materials were investigated: (1) titanium (Ti), (2) titanium nitride (TiN), (3) cobalt-chromium (CoCr), (4) zirconia (ZrO2), and (5) modified polyether ether ketone (m-PEEK). Both cell lines were cultured, expanded, and seeded in accordance with the protocol of their supplier. Cell proliferation and cytotoxicity were evaluated at days 1, 3, 5, and 10 using colourimetric viability and cytotoxicity assays. Data were analysed via two-way ANOVA, one-way ANOVA, and Tukey's post hoc test (p < 0.05 for all tests). Results: There was a statistically significant difference in cell proliferation of HGKC and HGFB cells in contact with different abutment materials at different time points, with no significant interaction between different materials. There was a significant effect on cell proliferation and cytotoxicity with different exposure times (p < 0.0001) for each material. Cell proliferation rates were comparable for both cell lines at the beginning of the study, however, HGFB showed higher proliferation rates for all materials at day 10 with better proliferation activities with ZrO and m-PEEK (40.27%) and (48.38%) respectively. HGKC showed significant interactions (p < 0.0001) in cytotoxicity between different materials. Conclusion: The present in vitro assessment investigated the biocompatibility of different abutment materials with soft tissue cells (HGFB and HGKC). The findings suggest that m-PEEK and TiN are biologically compatible materials with human cells that represent the soft tissue and can be considered as alternative implant abutment materials to Ti and ZrO2, especially when the aesthetic is of concern.


Comparison of the Efficacy and Safety of Metformin-Based Combination Therapy Versus Metformin Alone in Children and Adolescents With Type 2 Diabetes Mellitus: A Meta-Analysis.
The aim of this meta-analysis is to synthesize and critically evaluate the available evidence on the comparison of the efficacy and safety of metformin-based combination therapy versus metformin alone in children and adolescents with type 2 diabetes mellitus (T2DM). We performed the present meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible studies were identified using electronic searches for randomized controlled trials (RCTs) using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrial.gov from inception to 31 January 2023. The outcomes examined in this meta-analysis included change from baseline in glycated hemoglobin (HbA1C) (%), fasting plasma sugar (FPG) (mg/dl), and the number of individuals experiencing adverse events. Three studies met the criteria and were included in the meta-analysis. The reduction of HbA1C was significantly higher in metformin-based combination therapy (MD: -1.19, 95% CI: -2.05, -0.33, p-value: 0.007). No significant difference was reported between patients randomized in metformin-based combination therapy and metformin alone (MD: -18.67, 95% CI: -50.17, 12.84, p-value: 0.25). In conclusion, the present meta-analysis found that the reduction in HbA1C was significantly higher in patients receiving metformin-based combination therapy compared to metformin alone. No significant difference was found between the two groups in terms of the change in fasting plasma glucose (FPG) from the baseline. In relation to safety, no significant difference was found in the incidence of adverse events and serious adverse events between the two groups.


Tobacco use, Body Mass Index, and Potentially Malignant Disorders Among petrol fillers in Pimpri-Pune (India): A descriptive study.
Since petrol is combustible and smoking is banned at the petrol pumps, it may be predicted that use of smokeless tobacco is more prevalent among the petrol fillers. Also, smokeless tobacco is a major risk factor for developing oral potentially malignant disorders. The present study was conducted to determine the tobacco use, body mass index (BMI), and potentially malignant disorders among a cohort of petrol fillers and also to evaluate the interaction of tobacco use and BMI with the presence of potentially malignant disorders. The study was conducted at 45 petrol stations located at Pimpri-Pune, India. A descriptive study design was used. Four hundred and ten petrol fillers aged 17-64 years participated in the study. General information and tobacco history was obtained by interview. Height and weight were recorded to obtain BMI. Oral examination was conducted to identify the potentially malignant disorders. Chi-square test, Z test, and logistic regression were used. The level of significance was fixed at 5%. It was found that 242 (59.02%) used tobacco in different forms. 77.68% were tobacco chewers, and 8.26% were smokers. Leukoplakia was prevalent among 68.47%, oral submucous fibrosis among 27.45%, and 5.08% had erythroplakia. Age (χ(2) = 11.46, P < 0.05), duration (χ(2) = 17.46, P < 0.05), and frequency of tobacco chewing (χ(2) = 14.16, P < 0.05) were significantly associated with potentially malignant disorders. Tobacco chewing was more prevalent as compared to smoking. It can be concluded that the petrol fillers are at a high risk for developing oral potentially malignant disorders.


Integrodifferential diffusion equation for continuous-time random walk.
In this paper, we present an integrodifferential diffusion equation for continuous-time random walk that is valid for a generic waiting time probability density function. Using this equation, we also study diffusion behaviors for a couple of specific waiting time probability density functions such as exponential and a combination of power law and generalized Mittag-Leffler function. We show that for the case of the exponential waiting time probability density function, a normal diffusion is generated and the probability density function is Gaussian distribution. In the case of the combination of a power law and generalized Mittag-Leffler waiting probability density function, we obtain the subdiffusive behavior for all the time regions from small to large times and probability density function is non-Gaussian distribution.


The nature and origins of synovium: experimental approaches to the study of synoviocyte differentiation.
Synovium is characterised by an intimal layer of cells, now recognised to be a mixture of bone marrow-derived macrophages and specialised fibroblast-like cells. The fibroblast-like cells, or synoviocytes, differ from other fibroblasts in a number of respects, including high activity of uridine diphosphoglucose dehydrogenase (UDPGD) and constitutive expression of VCAM-1. Experiments have been devised to try to establish the factors that control these specialised features. Both high UDPGD activity and VCAM-1 expression can be seen in adventitious or regenerate connective tissue linings tissue under certain circumstances. Mechanical factors may be implicated in the induction of UDPGD activity and VCAM-1 expression, but there is evidence that they are controlled independently. The factors involved in synoviocyte differentiation both in the embryo and under conditions of regeneration or generation ab initio at adventitious sites in the adult require further investigation.


Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma.
Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated. To the best of our knowledge, this study is the first to test the effects of Sdc1 loss on colorectal tumor development in inflammation-driven colon tumorigenesis. Utilizing a mouse model of colitis-related colon carcinoma induced by the carcinogen azoxymethane (AOM), followed by the inflammatory agent dextran sodium sulfate (DSS), we found that Sdc1 deficiency results in increased susceptibility to colitis-associated tumorigenesis. Importantly, colitis-associated tumors developed in Sdc1-defficient mice were characterized by increased local production of IL-6, activation of STAT3, as well as induction of several STAT3 target genes that act as important effectors of colonic tumorigenesis. Altogether, our results highlight a previously unknown effect of Sdc1 loss in progression of inflammation-associated cancer and suggest that decreased levels of Sdc1 may serve as an indicator of colon carcinoma progression in the setting of chronic inflammation.


Bone marrow necrosis. acute microcirculation failure in myelomonocytic leukemia.
We saw bone marrow necrosis in a case of acute myelomonocytic leukemia. The diagnosis was made during the patinet's life, and the bone marrow microcirculation was studied immediately postmortem. Histology and injection of the bone marrow arteries showed an acute microcirculation failure. The pathogenesis and possible relationship with soluble immune complexes was studied.


Endovascular treatment for severe cerebral venous sinus thrombosis in a patient with polycythemia vera and nephrotic syndrome: a case report.
Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease that can occur at any age and generally has a good prognosis. Polycythemia vera and nephrotic syndrome are uncommon risk factors for cerebral venous sinus thrombosis. A dilemma exists in the treatment of cerebral venous sinus thrombosis with polycythemia vera and nephrotic syndrome, as some cases are refractory to first-line therapy. Here, we report a patient with CVST who presented with a generalized seizure and was found to have bilateral frontal lobe hemorrhage and subarachnoid hemorrhage. Brain magnetic resonance venography showed extensive cerebral venous sinus thrombosis extending from the superior sagittal sinus to the left internal jugular vein. Further testing revealed that the patient had polycythemia vera and nephrotic syndrome. Anticoagulation therapy had limited effects. He underwent endovascular intervention, including stent thrombectomy, intermediate catheter aspiration, balloon dilatation, and local intravenous thrombolysis, to achieve revascularization. After 9 months of follow-up, the patient had recovered well without any sequelae. This case shows that in patients with critical cerebral venous sinus thrombosis who fail to respond to anticoagulant therapy, stent thrombectomy combined with intermediate catheter aspiration, balloon dilation, and local thrombolysis may be a viable option. This strategy can quickly resolve venous sinus obstruction and improve the prognosis of patients with critical cerebral venous sinus thrombosis.


Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes.
Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity. Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO. CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors. WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO.


Robust Gait Recognition by Integrating Inertial and RGBD Sensors.
Gait has been considered as a promising and unique biometric for person identification. Traditionally, gait data are collected using either color sensors, such as a CCD camera, depth sensors, such as a Microsoft Kinect, or inertial sensors, such as an accelerometer. However, a single type of sensors may only capture part of the dynamic gait features and make the gait recognition sensitive to complex covariate conditions, leading to fragile gait-based person identification systems. In this paper, we propose to combine all three types of sensors for gait data collection and gait recognition, which can be used for important identification applications, such as identity recognition to access a restricted building or area. We propose two new algorithms, namely EigenGait and TrajGait, to extract gait features from the inertial data and the RGBD (color and depth) data, respectively. Specifically, EigenGait extracts general gait dynamics from the accelerometer readings in the eigenspace and TrajGait extracts more detailed subdynamics by analyzing 3-D dense trajectories. Finally, both extracted features are fed into a supervised classifier for gait recognition and person identification. Experiments on 50 subjects, with comparisons to several other state-of-the-art gait-recognition approaches, show that the proposed approach can achieve higher recognition accuracy and robustness.


Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension.
Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The aim of the current study was to examine the impact of prenatal GC exposure on the postnatal regulation of the gene encoding for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the biosynthesis of the catecholamine, epinephrine. PNMT has been linked to hypertension and is elevated in animal models of hypertension. Male offspring of Wistar-Kyoto dams treated with dexamethasone (DEX) developed elevated systolic, diastolic and mean arterial blood pressure compared to saline-treated controls. Plasma epinephrine levels were also elevated in adult rats exposed to DEX in utero. RT-PCR analysis revealed adrenal PNMT mRNA was higher in DEX exposed adult rats. This was associated with increased mRNA levels of transcriptional regulators of the PNMT gene: Egr-1, AP-2, and GR. Western blot analyses showed increased expression of PNMT protein, along with increased Egr-1 and GR in adult rats exposed to DEX in utero. Furthermore, gel mobility shift assays showed increased binding of Egr-1 and GR to DNA. These results suggest that increased PNMT gene expression via altered transcriptional activity is a possible mechanism by which prenatal exposure to elevated levels of GCs may program for hypertension later in life.


Association of the circadian factor Period 2 to p53 influences p53's function in DNA-damage signaling.
Circadian period proteins influence cell division and death by associating with checkpoint components, although their mode of regulation has not been firmly established. hPer2 forms a trimeric complex with hp53 and its negative regulator Mdm2. In unstressed cells, this association leads to increased hp53 stability by blocking Mdm2-dependent ubiquitination and transcription of hp53 target genes. Because of the relevance of hp53 in checkpoint signaling, we hypothesize that hPer2 association with hp53 acts as a regulatory module that influences hp53's downstream response to genotoxic stress. Unlike the trimeric complex, whose distribution was confined to the nuclear compartment, hPer2/hp53 was identified in both cytosol and nucleus. At the transcriptional level, a reporter containing the hp21(WAF1/CIP1) promoter, a target of hp53, remained inactive in cells expressing a stable form of the hPer2/hp53 complex even when treated with γ-radiation. Finally, we established that hPer2 directly acts on the hp53 node, as checkpoint components upstream of hp53 remained active in response to DNA damage. Quantitative transcriptional analyses of hp53 target genes demonstrated that unbound hp53 was absolutely required for activation of the DNA-damage response. Our results provide evidence of the mode by which the circadian tumor suppressor hPer2 modulates hp53 signaling in response to genotoxic stress.


Effect of 3,3'-iminodiproprionitrile (IDPN) on corticosteroidogenesis of isolated adrenocortical cells.
The neurotoxic agent, 3,3'-iminodiproprionitrile (IDPN), is a disrupter of neurofilament- and intermediate filament-organelle association. In the present study, the effect of IDPN on corticosteroidogenesis was investigated using isolated rat (having few intermediate filaments) and domestic fowl (having abundant intermediate filaments) adrenocortical cells. Cells were incubated with or without steroidogenic agents and precursors and with or without various concentrations of IDPN for 2 hr. IDPN had similar inhibitory potencies (as indicated by the half-maximal inhibitor concentrations (ID50 values] with both rat and domestic fowl cells despite their grossly different intermediate filament content. However, the average ID50 values of IDPN varied with the different steroidogenic agents and precursors used. The average IDPN ID50 values for maximal ACTH- and 8-bromo-cyclic AMP (8-Br-cAMP)-induced corticosterone production were equivalent (49.7 and 45.7 mM, respectively). However, the IDPN ID50 values for maximal ACTH-induced cAMP production, maximal 25-hydroxycholesterol- and pregnenolone-supported corticosterone production, and maximal ACTH- and 8-Br-cAMP-induced protein synthesis varied from 3.7 to 5.4 times the average ID50 values for maximal ACTH- and 8-Br-cAMP-induced corticosterone production. Thus, the inhibitory action of IDPN was not closely linked to the inhibition of ACTH-transmembrane signaling via cAMP, protein synthesis, and steroidogenic enzyme activity. The data suggest that IDPN inhibited corticosteroidogenesis at at a step after cAMP but before cholesterol side-chain cleavage and that the inhibition was not dependent on the presence of intermediate filaments.


A biosensor for all D-amino acids using evolved D-amino acid oxidase.
Determination of the D-amino acid content in foods and in biological samples is a very important task. In order to achieve this goal we developed a biosensor employing the flavoenzyme D-amino acid oxidase from the yeast Rhodotorula gracilis. To produce a device in which the D-amino acid composition does not alter the results, both the wild-type and a number of mutants obtained by rational design and directed evolution approaches were used. An analysis of D-amino acid oxidase mutants activity on D-amino acid mixtures containing various ratios of neutral, acidic, and basic substrates identified the Amberzyme-immobilized T60A/Q144R/K152E and M213G mutants as the best choice: their response shows an only limited dependence on the solution composition when at least 20% of the D-amino acid is made up of D-alanine (standard error is approximately 5-9%). This is the first report, to our knowledge, demonstrating that the entire D-amino acid content can be determined by using a screen-printed electrode amperometric biosensor, with a detection limit of 0.25 mM and a mean response time of 10-15 min. The D-amino acid assay based on R. gracilis DAAO-biosensor is inexpensive, simple to perform, and rapid: the D-amino acid concentration of a variety of biological samples can be investigated using this assay.


Ultrathin sandwich-like MoS2@N-doped carbon nanosheets for anodes of lithium ion batteries.
In this work, we report on a simple and scalable process to synthesize the core-shell nanostructure of MoS2@N-doped carbon nanosheets (MoS2@C), in which polydopamine is coated on the MoS2 surface and is then carbonized. An intensive investigation using transmission electron microscopy and Raman spectroscopy reveals that the as-synthesized MoS2@C possesses a nanoscopic and ultrathin layer of MoS2 sheets with a thin and conformal coating of carbon layers (∼ 3 nm). The MoS2@C demonstrates a superior electrochemical performances as an anode material for lithium ion batteries compared to exfoliated MoS2 and bulk MoS2 samples. This unique core-shell structure is capable of delivering an excellent Li(+) ion charging-discharging process as follows: a specific capacity as high as 1239 mA h g(-1), a high rate capability even at a high current rate of 10 A g(-1) while retaining 597 mA h g(-1), and a good cycle stability over 200 cycles at a high current rate of 2 A g(-1).


[Industrial preparative chromatography purification of 10-deacetylpaclitaxel, the enzymatic product of 7-xylosyl-10-deacetylpaclitaxel].
A scheme for industrial preparative chromatography purification of 10-deacetylpaclitaxel (10-DAP), the semi-synthesized precursor of anticancer drug paclitaxel was developed. 7-Xylosyl-10-deacetylpaclitaxel (10-DAXP) is the most abundant constitute in the needles of Taxus Chinensis, a specific yew species distributed in China. 10-DAXP has been recognized as a good material to convert into 10-DAP, the most ideal precursor of paclitaxel. The partially purified extract from yew needles which mainly contains 10-DAXP (> 60%) and other two minor 7-xylosyl-10-deacetyltaxanes including 7-xylosyl-10-deacetylcephalomannine (10-DAXC) and 7-xylosyl-10-deacetylpaclitaxel C (10-DAXP C), was used as the starting material. The total scheme can be divided into four steps. Firstly, the starting material was hydrolyzed by beta-xylosidase to remove the C-7 xylosyl group completely; and then the hydrolyzed products mainly containing 10-DAP were eluted on a column packed with resin to get crude 10-DAP (with the purity of 20.5%) with high yield (96.3%). The crude 10-DAP was purified by a column packed with normal phase, and then by a reversed-phase preparative chromatography with ODS as the solid phase. After these two steps, the purity of the aim product 10-DAP was 96% with the overall yield of 79.7%. This novel scheme was suitable for large-scale purification of 10-DAP from 10-DAXP.


The safety of asthma medications during pregnancy.
This article reviews the literature on asthma or use of antiasthmatic drugs during pregnancy, the impact on pregnancy and delivery outcome, and on the infant born. Some anomalies have been demonstrated. It is unclear if these are due to asthma or are the effect of antiasthma drug use. The former explanation appears to be most likely, and the outcome appears to co-vary with the severity of the disease. Therefore, an adequate therapy of asthma is important during pregnancy, and although a small increase in certain congenital malformations may exist, this is of little significance for the individual patient. Further efforts should be made to isolate the possible specific effects of antiasthmatic drugs, notably for recent additions to the therapeutic arsenal.


Monoclonal antibodies to human macrophage and leucocyte common antigens.
Three monoclonal antibodies have been made to identify cells of the human mononuclear phagocyte system in fluids and tissues. The first, PHM 1, recognises a surface antigen common to all leucocytes. The other 2 antibodies, PHM 2 and PHM 3, bind to monocytes and macrophages but not to polymorphonuclear cells (PMN). PHM 2 labels all monocytes, macrophages and a small population of T-cells. PHM 3 labels most monocytes and macrophages but no other blood cells. The application of these monoclonal antibodies to the identification of mononuclear phagocytes in blood and liver using an unlabelled antibody immunoperoxidase (PAP) technique is demonstrated.