In vitro activity of meropenem compared with imipenem, metronidazole, ampicillin, and ampicillin/sulbactam against anaerobes.
The aim of the present study was to compare the in vitro activity of meropenem (ICI 194660, CAS 96036-03-2) with imipenem, metronidazole, clindamycin, ampicillin and ampicillin/sulbactam against a variety of anaerobic bacteria using an agar dilution method. 423 clinical isolates were tested belonging to 70 species of 15 anaerobic genera. They included Bacteroides fragilis (n = 62), Bacteroides thetaiotaomicron (n = 45), Prevotella bivia (n = 11), Fusobacterium nucleatum (n = 12), Clostridium perfringens (n = 15) and several rarely isolated species and genera, e.g. Selenomonas sputigena and Clostridium symbiosum. Bacteroides species were inhibited by meropenem at < or = 2.0 micrograms/ml, Clostridium species, including C. difficile, at < or = 4.0 micrograms/ml and all the other anaerobes at < or = 0.5 microgram/ml. Meropenem and imipenem were the most active substances, but often equal to, or only slightly better than, metronidazole, clindamycin or ampicillin/sulbactam, dependent on species. Meropenem was especially active against Bacteroides gracilis (MIC90 0.015 microgram/ml), Prevotella disiens (MIC90 0.03 microgram/ml), Fusobacterium nucleatum (MIC90 0.015 microgram/ml), Clostridium perfringens (MIC90 0.015 microgram/ml) and Veillonella parvula (MIC90 0.03 microgram/ml). The results obtained indicate that meropenem might be a useful adjunct to chemotherapy of anaerobic and mixed aerobic and anaerobic infections.


Prenatal Exposure to Preeclampsia and Long-Term Ophthalmic Morbidity of the Offspring.
The aim of this population-based study was to evaluate whether prenatal exposure to preeclampsia poses a risk for long-term ophthalmic morbidity. A population-based cohort analysis compared the risk of long-term ophthalmic morbidity among children who were prenatally exposed to preeclampsia and those who were not. The study population was composed of children who were born between the years 1991 and 2014 at a single tertiary medical center. Total ophthalmic hospitalization and time-to-event were both evaluated. A Kaplan-Meier survival curve was conducted to compare cumulative ophthalmic hospitalization incidence based on the severity of preeclampsia. Confounders were controlled using a Cox regression model. A total of 242,342 deliveries met the inclusion criteria, of which 7279 (3%) were diagnosed with mild preeclampsia and 2222 (0.92%) with severe preeclampsia or eclampsia. A significant association was found between severe preeclampsia or eclampsia and the risk of long-term vascular-associated ophthalmic morbidity in the offspring (no preeclampsia 0.3%, mild preeclampsia 0.2% and severe preeclampsia or eclampsia 0.5%, p = 0.008). This association persisted after controlling for maternal age and ethnicity (adjusted hazard ratio (HR) 1.861, 95% CI 1.051-3.295). In conclusion, within our population, prenatal exposure to severe preeclampsia or eclampsia was found to be a risk factor for long-term vascular-associated ophthalmic morbidity in the offspring.


Enhancing spectral shifts of plasmon-coupled noble metal nanoparticles for sensing applications.
Noble metal nanoparticles possess very large scattering cross-sections, which make them useful as tags in biosensing assays with the potential to detect even single binding events. In this study, we investigated the effects of nanoparticle size on the shift in the light scattering spectrum following formation of Au-Au, Ag-Ag or Ag-Au dimers using FDTD simulations. We discuss the use of a color camera to detect these spectral changes for application in a target-induced dimerization sensing assay. Dimerization of Au nanoparticles induced a larger shift in color compared to Ag nanoparticles. Heterodimers composed of 60 nm Ag and 40 nm Au demonstrated an even larger spectral shift and color response compared to the best homodimer pair (80-40 nm Au). The increased spectral shift of the Ag-Au heterodimer was subsequently observed experimentally for the DNA-induced dimerization of nanoparticles, showing that careful selection of nanoparticle size and composition can significantly enhance recognition of nanoparticle dimerization events for use in (color) sensing assays.


sup-9, sup-10, and unc-93 may encode components of a two-pore K+ channel that coordinates muscle contraction in Caenorhabditis elegans.
Genetic studies of sup-9, unc-93, and sup-10 strongly suggest that these genes encode components of a multi-subunit protein complex that coordinates muscle contraction in Caenorhabditis elegans. We cloned sup-9 and sup-10 and found that they encode a two-pore K+ channel and a novel transmembrane protein, respectively. We also found that UNC-93 and SUP-10 colocalize with SUP-9 within muscle cells, and that UNC-93 is a member of a novel multigene family that is conserved among C. elegans, Drosophila, and humans. Our results indicate that SUP-9 and perhaps other two-pore K+ channels function as multiprotein complexes, and that UNC-93 and SUP-10 likely define new classes of ion channel regulatory proteins.


Temperature and transmural region influence functional measurements in unloaded left ventricular cardiomyocytes.
Intact cardiomyocytes are increasingly being used to investigate the molecular mechanisms of contraction and to screen new therapeutic compounds. The function of the cardiomyocytes is often measured from the calcium transients and sarcomere length profiles. We studied the role of experimental temperature and transmural region on indices of function in freshly isolated, unloaded cardiomyocytes. Intact cardiomyocytes were isolated from the subendocardium, midmyocardium, and subepicardium of 3-month-old Sprague-Dawley rats. Myocytes from each region were studied at 25°C, 31°C, and 37°C. Cytosolic calcium transients were measured using Fura-2 fluorescence, whereas sarcomere length shortening and relengthening profiles were measured using high-speed video capture. For both the calcium transients and sarcomere length profiles, the time to peak and the time to half relaxation decreased significantly with increasing temperature. Increasing temperature also raised the minimum and maximum calcium levels of all cells. Of note, there was a reduced coefficient of variation (standard deviation divided by the mean) at higher temperatures for calcium fluorescence amplitudes, time to peak calcium, and rates of sarcomeric shortening and relengthening. The amplitudes and minimum of the calcium transients were significantly dependent on transmural region, and several sarcomere length parameters exhibited statistical interactions between temperature and transmural region. Together, these results show that biological variability can be reduced by performing experiments at 37°C rather than at room temperature, and by isolating cells from a specific transmural region. Adopting these procedures will improve the statistical power of subsequent analyses and increase the efficiency of future experiments.


[Immediate complications of endovascular interventions in chronic ischemia of the lower extremity tissues].
The results of examination and treatment of 66 patients, suffering occlusion-stenotic affection of the lower extremities arteries, to whom transcutaneous transluminal balloon angioplasty was performed, are adduced. Immediate postoperative complications after endovascular interventions have occurred in 4 (6.1%) patients. The immediate complications, causes of their occurrence, methods of treatment, ways of prophylaxis were analyzed. In 50% of patients, suffering complications of endovascular interventions in immediate postoperative period, it is possible to eliminate them, using simple prophylactic measures.


Regulation of the RhoA/ROCK/AKT/β-catenin pathway by arginine-specific ADP-ribosytransferases 1 promotes migration and epithelial-mesenchymal transition in colon carcinoma.
Arginine-specific ADP-ribosytransferases 1 (ART1) is able to modify the arginine of specific proteins by mono-ADP-ribosylation. We previously reported that the expression of ART1 in human colon adenocarcinoma tissues was higher than in adjacent tissues. Herein, we primarily revealed that ART1 could regulate the epithelial-mesenchymal transition (EMT) and, therefore, the development of colon carcinoma. In CT26 cells, which overexpressed ART1 by lentiviral transfection, the following were promoted: alterations of spindle-like non-polarization, expression of EMT inducers and mesenchymal markers, migration, invasion and adhesion. However, epithelial marker expression was decreased. Correspondingly, knockdown of ART1 in CT26 cells had the opposite effects. The effect of ART1 on EMT and carcinoma metastasis was also verified in a liver metastasis model of BALB/c mice. To further explore the molecular mechanism of ART1 in EMT, CT26 cells were treated with several specific inhibitors and gene silencing. Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/β-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma.


Molecular simulation of the rheological properties and shear thinning principles of supramolecular drilling fluids at different burial depths.
In order to investigate the rheological properties and shear thinning principles of supramolecular drilling fluids, the salt-responsive supramolecular ionomer polymers with different components were designed and the change in shear viscosity of supramolecular polymer drilling fluid system with shear rate was studied using the molecular dynamics simulation method. The result indicated that the ionic supramolecular polymer drilling fluid system exhibits better self-assembly performance than the nonionic acrylamide drilling fluid system. Moreover, the drilling fluid system exhibits the best rheological properties and self-assembly performance when the feeding ratios of the three monomers in the two polymers are m : n : o = 5 : 90 : 5 and m : n : o = 30 : 40 : 30, respectively. The shear viscosity recovery rate of the #3 ionic supramolecular polymer drilling fluid system at different burial depths (1-5 km) is >87%, where the shear viscosity is mainly determined at ambient pressure. The shear thinning phenomenon of the supramolecular polymer drilling fluid system occurs because of the combined effect of the polymer molecular orientation and entanglement structure. When the shear rate is above a critical value, the polymer molecules are oriented along the flow field direction, decreasing the shear viscosity. However, when the shear rate is very high, the entanglement structure of the molecules is opened and the mesh structure of the fluids is disrupted, decreasing the shear viscosity of the drilling fluid.


Autonomic nervous system function in Huntington's disease.
To investigate whether Huntington's disease (HD) affects autonomic nervous system (ANS) functioning. Twenty patients with HD who had positive genetic test results underwent standardised ANS function tests including sympathetic skin responses (SSRs) of the hands and feet, measurements of heart rate variability (HRV), both during five minutes of resting and deep respiration, and an orthostatic blood pressure test. Patients were classified according to the motor subscale of the unified Huntington's disease rating scale (UHDRS; mean (SD) score 26.4 (13.6)) and divided into two subgroups: UHDRS <25 points (early stages, E-HD) and UHDRS > or =25 points (mid stages, M-HD). Autonomic indices were compared with those obtained for a group of well matched healthy controls (n=60). Overall, patients showed lower HRV indices than controls. Multivariate analysis with the independent factor of "group" (controls, E-HD, M-HD) showed a significant group effect on both the high frequency power (F=4.32, p=0.017) and the coefficient of variation (F=4.23, p=0.018), indicating a significant reduction in vagal modulation in the M-HD group. There was a shift in autonomic neurocardiac balance towards sympathetic predominance in the M-HD group compared with controls (F=2.89, p=0.062). Moreover, we found an inverse correlation between the severity of clinical HD symptoms (assessed by the UHDRS) and the modulation of cardiovagal activity (p=0.028). Vagal dysregulation was present in two patients; one of them also showed a pathological blood pressure test and a latency prolongation in the SSRs of the hands. Two other patients had pathologically reduced SSR amplitudes. Only patients of the M-HD group were affected. Autonomic dysfunction is present even in the middle stages of HD and affects both the sympathetic and parasympathetic branch of the ANS.


The origin of micronuclei induced by cytosine arabinoside and its synergistic interaction with hydroxyurea in human lymphocytes.
Using human lymphocytes and the cytokinesis-block micronucleus (CBMN) assay we have recently shown that excision-repairable DNA lesions induced by methylnitrosourea (MNU) and ultraviolet (UV) light (254 nm) can be converted to micronuclei (MNi) within one cell cycle if cytosine arabinoside (ARA-C) is added during the G1 phase of the cell cycle after mitogen stimulation. We have proposed that this conversion resulted from the inhibition by ARA-C of the gap-filling step during excision repair which results in the formation of single-stranded breaks at repair sites; these breaks are then converted to chromatid or chromosome breaks and subsequently to MNi on completion of nuclear division. To confirm this hypothesis we have examined the origin of MNi induced by ARA-C by using anti-kinetochore antibodies and found that between 77 and 86% of these MNi are kinetochore-negative which supports the idea that they originate mainly from acentric chromosome fragments. We have also demonstrated that combining ARA-C treatment with hydroxyurea (HU) during G1 provides a synergistic improvement in the conversion of spontaneous (4-fold increment) or MNU-induced (2-fold increment) excision-repairable DNA lesions to MNi when compared to the effects with ARA-C alone. HU treatment on its own did not influence micronucleus expression in untreated cells and cells treated with MNU.


[Myasthenia preceded by dysphonia. Clinical and electrophysical study].
The solely dysphonia symptom as atypical and relatively rare onset of myasthenia gravis is difficult to diagnose. We present 11 cases of myasthenia, where dysphonia was one and only one symptom of illness during several months to several years. The evidences of dysphonia were the fatigability and nasality of speech, as well as chronic hoarseness. The diagnosis of myasthenia was very difficult in this period and was often preceded by lengthy laryngological and neurological examination. In our paper we present the criteria proper for myasthenia diagnosis in which repetitive electrostimulation test and high-sensitive SFEMG method are used.


Mitogenomic phylogeny of nymphalid subfamilies confirms the basal clade position of Danainae (Insecta: Lepidoptera: Nymphalidae).
The phylogenetic relationships among the nymphalid subfamilies have largely been resolved using both morphological and molecular datasets, with the exception of a conflicting basal clade position for Libytheinae or Danainae that remains contentious between morphological and molecular studies. Several phylogenomic analyses have found that the danaine clade is sister to other nymphalid subfamilies; however, it largely depends on utilizing different molecular datasets, analysis methods, and taxon sampling. This study aimed to resolve the basal clade position and relationships among subfamilies and tribes of Nymphalinae by combining the most comprehensive available mitogenomic datasets with various analyses methods by incorporating a new Symbrenthia lilaea Hewitson sequence data. Phylogenetic relationships among 11 nymphalid subfamilies and the tribes of Nymphalinae were inferred by combining new and available mitogenomic sequence data from 80 ingroup and six outgroup species. The phylogenetic trees were reconstructed using maximum-likelihood (ML) and Bayesian inference (BI) methods based on five concatenated datasets: amino acid sequences and nucleotides from different combinations of protein-coding genes (PCGs), ribosomal RNA (rRNAs), and transfer RNA (tRNAs). Danainae is well-supported as the basal clade and sister to the remaining nymphalid subfamilies, except for the paraphyletic Libytheinae. Libytheinae was either recovered as a sister to the danaine clade followed by the satyrine clade or sister to the nymphaline + heliconiine clades, and is consistent with recent phylogenetic studies on Nymphalidae. The monophyletic Nymphalinae has been recovered in all analyses and resolves tribal-level relationships with high support values in both BI and ML analyses. We supported the monophyletic Nymphalini as a sister clade to Victorini, Melitaeini, and Kallimini + Junoniini with high supporting values in BI and ML analyses, which is consistent with previously published morphological and molecular studies.


The initiation of glycogen biosynthesis in rat heart alpha-1,4 glucans tightly associated with glycogen synthase.
A partially purified glycogen synthase from rat cardiac muscle transferred glucosyl residues from UDP-[14C]glucose to an endogenous protein acceptor in the absence of added primer. After native gel electrophoresis of the enzyme preparation, unprimed activity was detected. Primer-dependent and independent activities were found in the same position. After denaturing gel electrophoresis of the reaction products, radioactivity comigrated with protein. Pulse-chase experiments showed that the size of the reaction products increased as a function of time. These products were degraded by amyloglucosidase, thus suggesting that glycogen-like molecules had grown on the protein acceptor. The activity of the enzyme was markedly reduced upon preincubation with alpha-amylase. Therefore, preformed protein-bound alpha-1,4-glucans were acting as primers. The glucoprotein acceptor may be a protein strongly associated with glycogen synthase, or alternatively, the enzyme itself.


Influence of Pterygium on Corneal Biomechanical Properties.
To evaluate the influence of pterygium on corneal biomechanical properties as measured by the ocular response analyzer (ORA). ORA measurements of 48 eyes with primary nasal pterygium were compared with those of healthy fellow eyes. The mean age of the patients was 46.6 ± 18.9 years. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated IOP (IOPcc) were obtained for each subject by using the ORA (Reichert Ophthalmic Instruments, Depew, NY). CH and CRF were significantly lower in the eyes with pterygium than in the healthy fellow eyes (p1 = 0.011, p2 = 0.014, respectively). On the other hand, there were no significant differences between the eyes with pterygium and healthy fellow eyes concerning IOPg and IOPcc (p1 = 0.948, p2 = 0.129, respectively). The present study showed that biomechanical properties measured by ORA were affected by pterygium. The eyes with primary nasal pterygium had lower CH and CRF than healthy fellow eyes. Therefore, the effect of pterygium should be taken into account in order to make correct diagnoses by ORA.


Variability in measurement of Pithomyces chartarum spore counts.
AIMS To examine the agreement between spore counts of Pithomyces chartarum measured in a single aliquot of wash water with counts from multiple aliquots from the same 60 g pasture sample, and between spore counts measured in an individual 60 g pasture sample with counts from three 60 g pasture samples selected from the same 200 g paddock sample. MATERIALS AND METHODS Four Waikato dairy farms were visited once weekly from early January to late May 2013. One paddock, with 40 sampling sites, was selected per farm. At each visit, ∼200 g of pasture was collected per site. Spore counting was undertaken using a standard method, except that three separate 60 g pasture samples per 200 g paddock sample was counted; and for each 60 g pasture sample, spores were counted in 10 aliquots of wash water. The relationship between the results of a single aliquot and 6-10 aliquots of wash water from the same 60 g grass sample were assessed by calculating 95% prediction intervals. Limits of agreement analysis was used to assess the agreement between counts from one, two or three aliquots per 60 g pasture sample compared with 10 aliquots, and between counts from one and three 60 g pasture samples from the same 200 g paddock sample. RESULTS Comparing spore counts from individual aliquots with multiple aliquots resulted in large prediction intervals and 95% limits of agreement, which increased with increasing spore count. For an individual aliquot count of 2 spores, the 95% prediction interval for the count from 10 aliquots was 3-49 spores, and for an individual count of 10 spores the 95% prediction interval was 28-222 spores. Increasing the number of aliquots counted improved agreement. For a total count of 10 spores measured in 10 aliquots, the 95% limits of agreement, based on a single aliquot, were 2-50 spores, and for three aliquots were 5-20 spores. The agreement in spore counts measured in one compared with three 60 g pasture samples was moderate and also decreased with increasing spore count; the 95% limits of agreement were 4-14.5 for a mean spore count of 10. CONCLUSIONS AND CLINICAL RELEVANCE Measuring the spore counts of three aliquots of wash water per 60 g grass sample improved repeatability, and should be used as the standard technique, particularly when determining whether to start or finish facial eczema control programmes.


Balance, Basic Anthropometrics and Performance in Young Alpine Skiers; Longitudinal Analysis of the Associations During two Competitive Seasons.
Balance is hypothesized to be important in alpine skiing, while it is known that balance depends on anthropometric indices. The aim of this investigation was to explore the association between balance, anthropometrics and skiing-results over two competitive seasons among youth alpine-skiers. Eighty-one skiers (40 females) participated in this study. The participants were tested twice over two competitive seasons: when they were 12-13 years old (U14) and when they were 14-15 years old (U16). The variables consisted of anthropometrics (body height and body mass) and three balance indexes (medio-lateral-, anterio-posterior- and overall-stability-index). Additionally, skiing results in U14 and U16 were evaluated. The balance status did not change significantly over the observed period of time regardless of the significant changes in body mass and height. The relationships between balance and skiing results were higher in the U14 (Pearson's r = 0.45-0.54) than in the U16 (Pearson's r = 0.05-0.28). The relationships between anthropometrics and competitive results were generally stronger in girls (Pearson's r = 0.39-0.88) than in boys (Pearson's r = 0.26-0.58). After clustering athletes into three achievement groups on a basis of their competitive performance, discriminant canonical analysis showed that relationships between balance and skiing results decreased, while the relationships between anthropometrics and skiing results increased over the two observed seasons. This study highlighted the importance of balance in youth alpine skiing in the age range of 11-14 years.


Temperament and Character Differences in Patients with Premature Ejaculation.
The debate on the etiology of premature ejaculation is still ongoing although there was huge amount of biological and psychological theories. We aimed to investigate the personality structure of patients with premature ejaculation via temperament and character inventory. Forty patients with premature ejaculation and a matched number of healthy people were included. Participants were asked to fill out a questionnaire booklet with separate sections for general demographic information and the temperament and character inventory. Total novelty seeking scores and subscale 1 (exploration-excitability) scores in premature ejaculation patients were significantly higher than in control groups (p<0.05). Total harm avoidance scores and harm avoidance subscale 2 (fear of uncertainty) scores in premature ejaculation patients was found significantly lower than in control group (p<0.05). Beck depression score was significantly higher in patients with premature ejaculation than in control groups. Men with premature ejaculation are more impulsive (excitant), more tempered, more excitable and less prone to harmful behavior. Current findings tend to reinforce premature ejaculation based upon combination of neurobiological and psychological reasons.


Unrelenting time and ever-crazy workloads.
The sight of Big Ben and the sound of its iconic chime hold no romance for me. Instead, they make me shudder, even after all these years.


Labda-8(17),12,14-trien-19-oic acid contained in fruits of Cupressus sempervirens suppresses benign prostatic hyperplasia in rat and in vitro human models through inhibition of androgen and STAT-3 signaling.
Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 μM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.


A comparative study on retinal thickness of the macular region among AIDS patients with normal ocular fundus, HIV-related microvascular retinopathy patients, and cytomegalovirus retinitis patients.
The present study aims to measure the retinal thickness of the macular region of AIDS patients with normal ocular fundus, HIV-related microvascular retinopathy patients and cytomegalovirus retinitis (CMVR) patients by optical coherence tomography, and generalize the characteristics of retinal thickness of these 3 groups of patients.In this retrospective case series, the study object comprised of 111 AIDS patients who received diagnosis and treatment in the Ophthalmology Department of Beijing Youan Hospital. There are 33 patients in the AIDS normal ocular fundus group, 47 patients in the HIV-related microvascular retinopathy group, and 31 patients in the CMVR group. The retinal thickness of the macular region of these above patients was measured. The main indicators were retinal thickness of 9 macular partitions, best corrected visual acuity, CD4+ T lymphocyte count, and the start of highly active antiretroviral therapy.In the CMVR group, except for the nasal-outer and temporal-outer sectors, the thickness of the affected eye of the rest of the regions was greater than that of healthy eye (P < .05). Furthermore, there was a difference in thickness of the superior-outer and inferior-outer sectors between the AIDS normal ocular fundus group and HIV-related microvascular retinopathy group. The difference in thickness of the superior-inner sector between patients in the AIDS normal ocular fundus group and CMVR group was not statistically significant, while the difference in thickness of the rest of the regions was statistically significant. The difference in thickness of various regions between patients in the HIV-related microvascular retinopathy group and CMVR group was statistically significant.The retinal thickness of patients in the CMVR group generally increased, the retinal thickness of superior-outer and inferior-outer sections of patients in the HIV-related microvascular retinopathy group increased, when compared to the AIDS normal ocular fundus group. These optical coherence tomography (OCT) examination results present its own characteristics in different eye diseases in AIDS patients, and different stages of eye disease.


Systems approach to animal health services delivery in sub-Saharan Africa: the case of privatisation.
The theory of privatisation is first reviewed with respect to animal health care in sub-Saharan Africa. Then, using the systems approach advocated in an accompanying paper, the authors argue that the nature of animal production systems obtaining in any economy is of central importance in determining the type and mixture of animal health services delivery systems present. These are influenced, in turn, by the demand placed on the production system by consumers, the levels of consumer income and the policies enacted by governments. The authors compare the situation in sub-Saharan Africa with that in developed countries, especially the United States of America. Theory would predict that privatisation of veterinary services in sub-Saharan Africa will be evolutionary rather than revolutionary, even with deliberate policies to encourage privatisation. In regard to personnel, private services would be much easier to develop on the basis of auxiliaries and technicians, rather than self-employed veterinarians and their associates. Hasty or wholesale privatisation, involving the creation of a cadre of self-employed veterinarians will, in the face of market failure, result in a reduction in the services available to low input/low output production systems. The general level of animal health care provided to certain types of producers will thus be lower than currently available. These theoretical predictions are borne out in practice.


Adolescent girls in Denmark use oral contraceptives at an increasingly young age, and with more pauses and shifts.
Use of hormonal contraceptives for birth control is commonplace in the Western World. In Europe, there is considerable variety in the frequency of use of hormonal contraceptives and in the age at which these contraceptives are initiated. The purpose of the present study was to describe the use of hormonal contraceptives among the Danish adolescent female population, focusing on age, period and cohort effects and including types of hormonal contraceptives. All women aged 14-50 years during the 1995-2012 period were identified through the Central Person Register. Furthermore, the National Registry of Medicinal Products Statistics provided information on redeemed prescriptions for hormonal contraceptives characterised by Anatomical-Therapeutic-Chemical (ATC) classification codes. At the age of 17 years, more than 50% of the Danish adolescent population had redeemed a prescription for hormonal contraceptives. At the age of 20 years, 85% had ever used hormonal contraceptives. This amounts to a significant decrease in age at which hormonal contraceptives were initiated in the younger birth cohorts compared to the older cohorts. Additionally, adolescent girls have more pauses and shifts between types of hormonal contraceptives. Since 2010 there has been a shift toward use of second generation oral contraceptives away from third and fourth generation contraceptives. Adolescent girls tend to initiate their use of oral contraceptives at a younger age than the older cohorts do. Furthermore, they have more pauses and shift between products more frequently than older cohorts. The type of oral contraceptive used has shifted since 2010 towards older products with second generation progestins. The study was funded by salaries from North Zealand Hospital. The study was approved by the Danish Data Protection Agency (J. No. 2010-41-4778).


Prevalence of Tics Among 6- to 12-Year-Old Schoolchildren in the Itagui Municipality, Colombia, in 2010.
Tics are the most frequent movement disorder in children and they are most prevalent during the school-age years. Most tics are transitory; however, certain tics can be chronic, causing negative repercussions at school, within the family, and socially. In some cases, tics are associated with obsessive compulsive disorder, attention-deficit hyperactivity disorder (ADHD) and other conditions that require diagnosis and prompt treatment. In South America, there are no indexed studies determining the prevalence of tics in school-age children. The aim of this study was to establish the prevalence of tics in schoolchildren aged 6 to 12 years. From 16 000 students aged 6 to 12 years who were enrolled in first to fifth grade, a sample of 346 school-aged children was chosen via a multistage sampling process that randomized the educational systems in terms of proportional size and the stratification between public and private schools and adjusted for the design effect. The students were screened and those who were positive for tics underwent clinical evaluations and semistructured interviews by the researchers to determine the prevalence of the disease. The parents and teachers of 323 students returned our surveys (93.3%). One hundred thirty-eight students (42.7%) were considered positive for tics based on parents' and teachers' reports. The clinical evaluation established a 17.97% prevalence of tics (58 students), and 25 students (43.2%) also met diagnostic criteria for ADHD. Of the students with tics, 27.6% presented with transitory tics, and 72.4% presented with chronic tics. Gilles de la Tourette syndrome was detected in 11 of the children (3.4%). The average age of child with tics was 9 ± 1.5 years, and the majority of the children with tics attended third grade at a basic primary school. Children from public and private schools were equally likely to present with tics. Tics are noteworthy in our field and are associated with other neurobehavioral disorders, such as ADHD. Both tic disorders and ADHD require diagnosis and prompt treatment to promote social and school performance.


Appraisal and ranking of poly-aluminium chloride, ferric chloride and alum for the treatment of dairy soiled water.
Land spreading of dairy soiled water (DSW) may result in pollution of ground and surface waters. Treatment of DSW through sludge-supernatant separation using chemical coagulants is a potential option to reduce the negative environmental impacts of DSW. The aims of this study were to (1) assess the effectiveness of three chemical coagulants - poly-aluminium chloride (PACl), ferric chloride (FeCl3) and alum - in improving effluent quality, and (2) assess the properties of the sludge that is generated as by-product from the process for its suitability for land application. Taking into consideration optimum doses to minimize pollutants (turbidity, chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), and E. coli), optimum mixing times and cost, FeCl3 was the best performing coagulant. Generated sludges had higher nutrient content and fewer E. coli than raw DSW, and did not display any evidence of phytotoxicity to the growth of Lolium perenne L. using germination tests. The study discussed the results in a sustainable farm management context, and suggested that the effluent (supernatant) from the treatments may be recycled to wash farm yards, saving water. In parallel, the sludge portion can be applied to amend soil properties with no adverse impacts on the grass growth, providing an agronomic value as an organic fertilizer, and reducing the risk of nutrient losses. This management approach could minimize the overall net cost compared to land application of raw DSW.


Anionic glycerophospholipids in platelets from alcoholics.
Studies on ethanol-exposed animals have revealed changes in anionic phospholipids in brain membranes. The intention of this study was to investigate whether there was a similar effect on man. Assuming platelets to be an adequate model for CNS synaptosomes, concentration and fatty acid composition of anionic phospholipids, phosphatidylserine (PS) and phosphatidylositol (PI) in the platelet membrane from alcoholics after a debauche period were examined and compared to controls. Ethanol effects on neutral lipids were also analysed in order to obtain a comprehensive view. No quantitative difference was found in anionic phospholipids between alcoholics and controls. Fatty acid composition of individual phospholipids revealed significant changes which were more obvious in neutral phospholipids than in anionic. Oleic acid was increased and linoleic and arachidonic acids were decreased. After 1 week of detoxification, the abnormalities did not decrease, on the contrary they increased and total phospholipid concentration per platelet was significantly higher than in controls. It is concluded that the ethanol toxicity on bone marrow hampers the use of platelets as a model for synaptosomes but that the observed lipid abnormalities might play a major role in the impairment of platelet function in alcoholics.


School health promotion in South-East Asia by Japan and partners.
School health promotion in South-East Asia has developed rapidly in recent years, and Japan has been one of the significant contributors to the reinforcement of school health promotion in the region. Starting from the Hashimoto Initiative on global parasite control, Japan advocated for international partnerships with several agencies for the development of school health programs in South-East Asia. Through a strengthened collaboration with international organizations, countries such as the Lao PDR, Cambodia, the Philippines, and Thailand have created and implemented school health programs on nutrition, sanitation, and deworming, among others. In addition to school health program formulation and implementation, the expanded network in South-East Asia led to more capable school health personnel, with many workers in the education and health sectors benefitting from the training programs jointly held by collaborating organizations.


Integrated analysis of miRNA-mRNA regulatory networks of potato (Solanum tuberosum L.) in response to cadmium stress.
Cadmium (Cd) stress is a ubiquitous abiotic stress affecting plant growth worldwide and negatively impacting crop yield and food safety. Potato is the most important non-grain crop globally, but there is limited research available on the response of this crop to Cd stress. This study explored the coping mechanism for Cd stress in potato through analyses of miRNA and mRNA. Tissue culture seedlings (20-day-old) of potato variety 'Atlantic' were cultured for up to 48 h in liquid medium containing 5 mmol/L CdCl2, and phenotypic, physiological, and transcriptomic changes were observed at specific times. With the extension of Cd stress time, the potato leaves gradually wilted and curled, and root salicylic acid (SA), glutathione (GSH), and lignin contents and peroxidase (POD) activity increased, while indole-3-acetic acid (IAA) and zeatin (ZT) contents decreased. Using miRNA-seq, 161 existing miRNAs, 383 known miRNAs, and 7361 novel miRNAs were identified, and, 18 miRNAs were differentially expressed in response to Cd stress. Based on mRNA-seq, 7340 differentially expressed mRNAs (DEGs) were found. Through mRNA-miRNA integrated analysis, miRNA-target gene pairs consisting of 23 DEGs and 33 miRNAs were identified. Furthermore, "glutathione metabolism" "plant hormone signal transduction" and "phenylpropanoid biosynthesis" were established as crucial pathways in the Cd stress response of potato. Novel miRNAs novel-m3483-5p and novel-m2893-5p participate in these pathways through targeted regulation of cinnamic alcohol dehydrogenase (CAD; PG0005359) and alanine aminotransferase (POP; PG0024281), respectively. This study provides information that will help elucidate the complex mechanism of the Cd stress response in potato. Moreover, candidate miRNAs and mRNAs could yield new strategies for the development of Cd-tolerant potato breeding.


Diaphanous homolog 3 (Diap3) overexpression causes progressive hearing loss and inner hair cell defects in a transgenic mouse model of human deafness.
We previously demonstrated that a mutation in the 5' untranslated region of Diaphanous homolog 3 (DIAPH3) results in 2 to 3-fold overexpression of the gene, leading to a form of delayed onset, progressive human deafness known as AUNA1 (auditory neuropathy, nonsyndromic, autosomal dominant, 1). To investigate the mechanism of deafness, we generated two lines of transgenic mice overexpressing Diap3, the murine ortholog of DIAPH3, on an FVB/NJ background. Line 771 exhibits a relatively mild 20 dB hearing loss at 12 kHz at 4 and 8 weeks of age, progressing to 40 dB and 60 dB losses at 16 and 24 weeks, respectively, at 12 and 24 kHz. Line 924 shows no hearing loss at 4 or 8 weeks, but manifests 35 and 50 dB threshold shifts at 16 and 24 weeks, respectively, at both 12 and 24 kHz. Notably, mice from the two transgenic lines retain distortion product otoacoustic emissions, indicative of normal cochlear outer hair cell (OHC) function despite elevation of auditory thresholds. Scanning electron microscopy of the organ of Corti demonstrates striking anomalies of the inner hair cell (IHC) stereocilia, while OHCs are essentially intact. Over time, IHCs of both lines develop elongated stereocilia that appear fused with neighboring stereocilia, in parallel to the time course of hearing loss in each line. Furthermore, we observe significant reduction in the number of IHC ribbon synapses over 24 weeks in both lines, although this reduction does not correlate temporally with onset and progression of hearing loss or stereociliary anomalies. In summary, overexpression of wild-type Diap3 in two lines of transgenic mice results in hearing loss that recapitulates human AUNA1 deafness. These findings suggest an essential role of Diap3 in regulating assembly and/or maintenance of actin filaments in IHC stereocilia, as well as a potential role at the IHC ribbon synapse.


Mixed state discrimination using optimal control.
We present theory and experiment for the task of discriminating two nonorthogonal states, given multiple copies. We implement several local measurement schemes, on both pure states and states mixed by depolarizing noise. We find that schemes which are optimal (or have optimal scaling) without noise perform worse with noise than simply repeating the optimal single-copy measurement. Applying optimal control theory, we derive the globally optimal local measurement strategy, which outperforms all other local schemes, and experimentally implement it for various levels of noise.


Synthesis and characterization of carbohydrate-based phospholipids.
Novel carbohydrate-based phospholipids containing two saturated C(12) (dilauroyl ribo-phosphocholine) (DLRPC), C(14) (dimyristoyl ribo-phosphocholine) (DMRPC), and C(20) (diarachadonyl ribo-phosphocholine) (DARPC) carboxylic acid chains were synthesized. The physical properties of the supramolecular structures formed by these compounds were compared to those formed by their direct glycerol analogues dilauroyl phosphocholine (DLPC), dimyristoyl phosphocholine (DMPC), and diarachadonyl phosphocholine (DAPC). Modulated differential scanning calorimetry (MDSC) and X-ray diffraction data indicated that with chain lengths < or =14 carbons, the carbohydrate backbone increased the thermal stability of the bilayer below the phase-transition temperature (T(m)) as compared to the glycerol-based lipids. With longer chains (C(20)), the bilayer structure was destabilized as compared to glycerol-based lipids. NMR studies of a DMRPC vesicle dispersion reveal split choline headgroup signals and distinct magnetization transfer effects arising from the "inner" and "outer" surfaces of the bilayer vesicle. Modulated differential scanning calorimetry also demonstrated that glycerol- and carbohydrate-based lipids mix, as evidenced by a single intermediate T(m). In addition, carbohydrate-based lipid/cholesterol mixtures exhibited a decrease in enthalpy with an increase in cholesterol concentration. Unlike glycerol phospholipids, carbohydrate lipids were resistant to enzymatic degradation by phospholipase A(2) (PLA(2)).


Determining the optimal protocol for preparing an acellular scaffold of tissue engineered small-diameter blood vessels.
Although detergent-based decellularization protocols have been widely used to obtain a natural extracellular matrix (ECM) scaffold in tissue engineering, some key challenges still exist. To achieve an optimum natural decellularized scaffold for the construction of tissue-engineered small-diameter blood vessels (TEBV), porcine carotid arteries (PCAs) were decellularized by combining sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC) and Triton X-100 (Triton) in different concentrations. Tissue samples were processed and their histological, biochemical and biomechanical characteristics were investigated. Results showed that only two methods 0.5% (SDS + SDC) and 1% (SDS + SDC) could completely remove of the cellular contents and preserve the native ECM architecture. Furthermore, 1% (SDS + SDC) based methods acquire preferable porosity and suitable mechanical strength. Residual Triton in the ECM scaffold holds intensive cytotoxity. In conclusion, 1%(SDS + SDC) based method can obtain a superior PCAs scaffold for the construction of TEBV. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 619-631, 2018.


Profile of infliximab in the treatment of pediatric Crohn's disease.
In recent years, a novel biologic therapy with monoclonal antibodies against tumor necrosis factor-alpha has revolutionized the treatment of Crohn's disease. Infliximab, the first biologic agent, has been demonstrated to considerably improve both clinical and endoscopic outcomes. In view of the growing popularity of infliximab in the management of Crohn's disease, we review the profile of the agent in the treatment of this disease in a pediatric setting.


Neuropsychiatric and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder.
Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD. The CD + ADHD group had increased left-sided soft signs compared with the CD group. CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests. Results are discrepant with previous findings of deficient verbal functioning in delinquent populations. However, findings may not be generalizable because of sampling limitations.


Site-directed mutagenesis probing the catalytic role of arginines 165 and 166 of human cytomegalovirus protease.
Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and Epstein-Barr virus (EBV). Each member of this family encodes a serine protease that is a potential target for antiviral therapeutic intervention. We recently reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella, A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid, S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165 and Arg166 residues are involved in stabilizing the oxyanion intermediate in human herpes protease catalyzed reactions through the backbone NH and side chain, respectively. In the current study, site-directed mutagenesis was carried out to probe the catalytic function of these two amino acid residues. Substitution of Arg166 with an alanine has led to ablation of enzymatic activity without detectable change in CMV protease conformation, supporting suggestions from the crystal structure that Arg166 side chain plays a major role in catalysis. The wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was shown previously to hold a water molecule that can act as a hydrogen-bond donor to the oxyanion and was thus proposed to stabilize the oxyanion intermediate. However, kinetic characterization of the mutant R165A only reveals a 2.7-fold lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/- 0.4 min-1. These results confirm that Arg165 side chain is not involved in the stabilization of the oxyanion. It is likely that Arg165 only utilizes the backbone NH for catalysis as suggested by the crystal structure.


Developmental expression of the cellular prion protein (PrP(C) ) in bovine embryos.
The mammalian cellular prion protein (PrP(C) ) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or PrP(Sc) ), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (TSEs). Although much is known about PrP(Sc) conversion and its role in TSEs, the normal function of PrP(C) has not been elucidated. In adult mammals, PrP(C) is most abundant in the central nervous tissue, with intermediate levels in the intestine and heart, and lower levels in the pancreas and liver. PrP(C) is expressed during neurogenesis throughout development, and it has recently been proposed that PrP(C) participates in neural cell differentiation during embryogenesis. In order to establish the developmental timing and to address the cell-specific expression of PrP(C) during mammalian development, we examined PrP(C) expression in bovine gametes and embryos through gestation Day 39. Our data revealed differential levels of Prnp mRNA at Days 4 and 18 in pre-attachment embryos. PrP(C) was detected in the developing central and peripheral nervous systems in Day-27, 32-, and -39 embryos. PrP(C) was particularly expressed in differentiated neural cells located in the marginal regions of the central nervous system, but was absent from mitotically active, periventricular areas. Moreover, a PrP(C) cell-specific pattern of expression was detected in non-nervous tissues, including liver and mesonephros, during these stages. The potential participation of PrP(C) in neural cell differentiation is supported by its specific expression in differentiated states of neurogenesis.


Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo.
The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has multiple antitumor effects against a variety of human cancers. We treated several anaplastic and papillary thyroid cancer cell lines with SAHA to determine if it could inhibit the growth of these cells in vitro and in vivo. SAHA effectively inhibited 50% clonal growth of the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid cancer cell line, BHP 7-13, at 1.3x10(-7) to 5x10(-7) mol/L, doses that are achievable in patients. In concert with growth inhibition, SAHA down-regulated the expression of cyclin D1 and up-regulated levels of p21WAF1. Annexin V and cleavage of poly(ADP)ribose polymerase were both increased by exposure of the thyroid cancer cells to SAHA. Expression of the death receptor 5 (DR5) gene was also increased by SAHA, but the combination of the DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with SAHA had little effect compared with SAHA alone. Of note, the combination of paclitaxel, doxorubicin, or paraplatin with SAHA enhanced cell killing of the thyroid cancer cells. In addition, murine studies showed that SAHA administered daily by i.p. injection at 100 mg/kg inhibited the growth of human thyroid tumor cells. Our data indicate that SAHA is a plausible adjuvant therapy for thyroid cancers.


Routine computed tomography in the evaluation of vocal fold movement impairment without an apparent cause.
Routine computed tomography (CT) for vocal fold movement impairment (VFMI) without an apparent cause is common. However, given increased cancer risk associated with ionizing radiation exposure, our purpose is to evaluate the utility of routine scans for these patients. Retrospective case series. Houston, Texas. A 5-year review of patients with VFMI diagnosed at an academic institution was conducted. For patients without an apparent cause (eg, recent head, neck, or cardiothoracic surgery or known malignancy), CT head/neck and chest was performed to evaluate the recurrent laryngeal nerve course. Data included demographics, symptoms, radiography, and interventions. Statistical analyses were performed via χ(2) analysis. Of 406 patients with VFMI, 47 (11%) patients had no apparent cause clinically. Routine CT revealed abnormalities in 10 (21%) patients, of which only 3 (6%) could account for VFMI: benign thyroid adenoma (1), papillary thyroid cancer (1), and an esophageal mass (1). The most common lesion detected involved the thyroid. Demographic data and symptom type were not significantly associated with detection of a VFMI-attributable lesion on CT. Overall, routine CT did not identify a focal etiology in 94% patients with VFMI without an apparent cause. Routine pan-CT evaluation failed to reveal an etiology in 94% of patients with VFMI without an apparent cause. Patients may be subjected to health risks associated with radiation exposure without significant diagnostic benefit. Further studies should consider more judicious use of CT in the context of risk factors and safer imaging modalities as the initial diagnostic step.


High-Throughput Fabrication Method for Producing a Silver-Nanoparticles-Doped Nanoclay Polymer Composite with Novel Synergistic Antibacterial Effects at the Material Interface.
In this study, we report a high-throughput fabrication method at industrial pilot scale to produce a silver-nanoparticles-doped nanoclay-polylactic acid composite with a novel synergistic antibacterial effect. The obtained nanocomposite has a significantly lower affinity for bacterial adhesion, allowing the loading amount of silver nanoparticles to be tremendously reduced while maintaining satisfactory antibacterial efficacy at the material interface. This is a great advantage for many antibacterial applications in which cost is a consideration. Furthermore, unlike previously reported methods that require additional chemical reduction processes to produce the silver-nanoparticles-doped nanoclay, an in situ preparation method was developed in which silver nanoparticles were created simultaneously during the composite fabrication process by thermal reduction. This is the first report to show that altered material surface submicron structures created with the loading of nanoclay enables the creation of a nanocomposite with significantly lower affinity for bacterial adhesion. This study provides a promising scalable approach to produce antibacterial polymeric products with minimal changes to industry standard equipment, fabrication processes, or raw material input cost.


Legal considerations for treatment following trauma to teeth.
When treating an orally traumatized patient, the dentist has no fewer professional and legal responsibilities than when treating a nonemergency patient. After obtaining proper consent, the examination, diagnosis, treatment, and follow-up of the patient must not be made negligently. Minimally, the dentist must not practice below the standard of care of a similar practitioner acting in the same or similar circumstances. The dentist also may be called on to further assist that patient in his or her attempt to obtain compensation for loss brought about by the trauma.


Not an Aspirin: No Evidence for Acute Anti-Nociception to Laser-Evoked Pain After Motor Cortex rTMS in Healthy Humans.
High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown efficacy in relieving neuropathic pain. Whether its analgesic effect also applies to acute physiological nociception remains unclear due to previous contradictory findings. To provide an in-depth investigation of the effects of motor cortex HF-rTMS on acute laser-evoked pain and excitability of nociceptive networks in healthy subjects. Randomized, placebo-controlled, double-blind, cross-over study in 20 healthy participants. Laser heat stimuli at nociceptive threshold were delivered to the right hand, allowing assessment of: (a) subjective pain intensity and unpleasantness; (b) laser-evoked potentials (LEPs, 128 electrodes) and their source model; (c) sympathetic skin responses, and (d) spino-thalamic pathway excitability. Data were collected before and 20 minutes after a session of neuro-navigated 20 Hz rTMS to the contralateral motor cortex. Subjective pain reports to thermal laser pulses, amplitude of late cortical potentials and sympathetic skin responses were decreased after cortical stimulation, to a similar extent whether it was active or placebo. Early cortical potentials and nociceptive network excitability remained identical before and after rTMS, as did anatomical sources of LEPs. Our results do not provide evidence for a genuine anti-nociceptive effect of rTMS on acute physiological pain. We suggest that motor cortex rTMS may act upon high-order networks linked to the emotional and cognitive appraisal of chronic pain, and/or modulate pathologically sensitized networks, rather than change the physiological transmission within an intact nervous system. Such dichotomy is reminiscent of that observed with most drugs used for neuropathic pain.


20S proteasome prevents aggregation of heat-denatured proteins without PA700 regulatory subcomplex like a molecular chaperone.
The eukaryotic 20S proteasome is the multifunctional catalytic core of the 26S proteasome, which plays a central role in intracellular protein degradation. Association of the 20S core with a regulatory subcomplex, termed PA700 (also known as the 19S cap), forms the 26S proteasome, which degrades ubiquitinated and nonubiquitinated proteins through an ATP-dependent process. Although proteolytic assistance by this regulatory particle is a general feature of proteasome-dependent turnover, the 20S proteasome itself can degrade some proteins directly, bypassing ubiquitination and PA700, as an alternative mechanism in vitro. The mechanism underlying this pathway is based on the ability of the 20S proteasome to recognize partially unfolded proteins. Here we show that the 20S proteasome recognizes the heat-denatured forms of model proteins such as citrate synthase, malate dehydrogenase. and glyceraldehydes-3-phosphate dehydrogenase, and prevents their aggregation in vitro. This process was not followed by the refolding of these denatured substrates into their native states, whereas PA700 or the 26S proteasome generally promotes their reactivation. These results indicate that the 20S proteasome might play a role in maintaining denatured and misfolded substrates in a soluble state, thereby facilitating their refolding or degradation.


Abnormal placental villous maturity and dysregulated glucose metabolism: implications for stillbirth prevention.
In the UK one in 250 pregnancies end in stillbirth. Abnormal placental villous maturation, commonly associated with gestational diabetes, is a risk factor for stillbirth. Histopathology reports of placental distal villous immaturity (DVI) are reported disproportionately in placentas from otherwise unexplained stillbirths in women without formal diagnosis of diabetes but with either clinical characteristics or risk factors for diabetes. This study aims to establish maternal factors associated with DVI in relation to stillbirth. Placental histopathology reports were reviewed for all pregnant women delivering at University College London Hospital between July 2018 to March 2020. Maternal characteristics and birth outcomes of those with DVI were compared to those with other placental lesions or abnormal villous maturation. Of the 752 placental histopathology reports reviewed, 11 (1.5%) were reported as diagnostic of DVI. Eighty cases were sampled for clinical record analysis. All women with DVI had normal PAPP-A (>0.4 MoM), normal uterine artery Doppler studies (UtA-PI) and were normotensive throughout pregnancy. Nearly one in five babies (2/11, 18.5%) with DVI were stillborn and 70% had at least one high glucose test result in pregnancy despite no formal diagnosis of diabetes. These findings suggest that the mechanism underlying stillbirth in DVI likely relates to glucose dysmetabolism, not sufficient for diagnosis using current criteria for gestational diabetes, resulting in placental dysfunction that is not identifiable before the third trimester. Relying on conventional diabetes tests, foetal macrosomia or growth restriction, may not identify all pregnancies at risk of adverse outcomes from glucose dysmetabolism.


Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound Polysaccharide-K in Tumor-bearing Mouse Models.
We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK). PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines. PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8+ T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60. We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model.


Increasing the interval between initiation and the onset of exposure to orotic acid decreases its promoting effect on rat liver carcinogenesis.
The present study was designed to determine whether a delay in the start of the promoting regimen after the administration of a carcinogen would influence the promoting efficacy of orotic acid on the development of hepatocellular carcinoma in rats. Male Fischer 344 rats weighing 130-150 g were injected with a single dose of diethylnitrosamine (200 mg/kg body wt i.p.) then divided into 3 groups: groups 1 and 2 were given semi-synthetic basal diet or the same diet containing 1% orotic acid (OA) respectively starting 1 week after the carcinogen; group 3 received the OA diet starting 5 weeks after the administration of diethylnitrosamine. Animals from these 3 groups were sacrificed after 25, 32, 42 and 60 weeks of being fed their respective diets. The results indicated that delaying the start of the OA diet after the carcinogen resulted in about a 50% decrease in the incidence of hepatic nodules and/or hepatocellular carcinomas at various time points during the experiment. This decrease in promoting efficacy of OA was not apparently explainable by lack of metabolic effects of OA, at least in terms of induction of nucleotide pool imbalance, a condition that appears to be important for OA to exert its tumor promoting effects.


Distal splenorenal shunt in treatment of bleeding esophageal varices in renal transplant recipients.
We conclude from this study that bleeding esophageal varices may occur as a late complication of liver disease associated with chronic renal failure and renal transplantation. In two of the three patients reported upon, the liver disease was probably determined on the basis of cirrhosis, secondary to chronic, active hepatitis from non-A, non-B hepatitis, while the third patient had hepatic fibrosis. Such bleeding is best controlled by selective variceal decompression with a DSRS. Finally, it is technically feasible to perform a DSRS upon some patients following a left nephrectomy, and the renal vein is of adequate caliber even in the presence of nonfunctioning kidneys.


Agreement on Interpretation of Point-of-Care Ultrasonography for Cardiac Tamponade Among Emergency Physicians.
Cardiac tamponade is an impending calamitous disorder that emergency physicians need to consider and diagnose rapidly. A pericardial effusion with right atrial systolic collapse (earliest sign) or right ventricular diastolic collapse (most specific sign) and a plethoric inferior vena cava are indicators of cardiac tamponade physiology and may be identified with point-of-care ultrasonography (POCUS). The goal of this study is to assess the agreement among emergency physicians with varying levels of sonographic training and expertise in interpreting echocardiographic signs of cardiac tamponade in adult patients. Methods: Emergency physicians at different levels of training as sonographers were surveyed at didactic conferences at three major academic medical centers in northern New Jersey. Two cardiologists were also included in the study for comparison. Survey respondents were shown 15, 20-second video clips of patients who had presented to the emergency department (ED) with or without significant pericardial effusions and were asked to rate whether tamponade physiology was present or not. Data were collected anonymously on Google Forms (Google LLC, Mountain View, CA) and included self-reported levels of POCUS expertise and level of training. Data were analyzed using Fleiss' kappa (k). All patients had an echocardiogram performed by the department of cardiology within 24 hours of the POCUS, and the results are presented in the paper. Results: There were 97 participant raters, including attendings, fellows, and resident physicians specializing in adult emergency medicine and two cardiologists. There was a fair degree of inter-rater agreement among all participants in interpreting whether tamponade physiology was present or not. This low level of agreement persisted across self-reported training levels and self-reported POCUS expertise, even at the expert level in both emergency medicine and cardiology specialties. According to the results of our study, there appears to be a low level of agreement in the interpretation of cardiac tamponade in adult patients. The lack of agreement persisted across specialties, self-reported training levels, and self-reported ultrasonographic expertise. This low level of agreement seen among both specialists indicates that emergency physicians are not limited in their ability to determine cardiac tamponade on POCUS. This highlights the technical nature of POCUS clips and strengthens the importance of physical exam findings when diagnosing cardiac tamponade in emergency department patients. Further research utilizing POCUS for the diagnosis of tamponade is warranted.


Microheterogeneity around the reactive lysine residue in the myosin heavy chain from rabbit skeletal muscle.
A molecule of myosin subfragment 1 (S1) from rabbit skeletal muscle has one highly reactive lysine residue, Lys-83 (RLR), in the heavy chain, which is rapidly and stoichiometrically modified by trinitrobenzenesulfonate. Our previous kinetic study (Komatsu, H., Emoto, Y., and Tawada K. (1993) J. Biol. Chem. 268, 7799-7808) showed that although MgPPi reduces the maximum number of trinitrophenylated RLR down to about 0.5 mol/mol of S1, this half-stoichiometric modification of RLR is not the result of any heterogeneity in the primary structure of S1. However, this result conflicts with a previous report in which the half-stoichiometric trinitrophenylation has been reported to be related to Pro/Ser microheterogeneity at the 78th residue position in the heavy chain of rabbit skeletal muscle myosin. To resolve the conflict, we isolated peptides containing both the 78th residue and RLR from the two different preparations of S1, one whose RLR was trinitrophenylated in the presence of MgPPi and the other whose RLR was not trinitrophenylated in the presence of MgPPi, and then we determined the amino acid sequences of the peptides. We found the same Pro/Ser microheterogeneity at the 78th position in the peptides from these S1s and thus concluded that this microheterogeneity has no correlation to the half-stoichiometric trinitrophenylation of RLR.


β-GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice.
Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. β-guanidinopropionic acid (β-GPA) supplementation decreases high-energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered β-GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively). Relative [PCr] and PCr/ATP ratios significantly decreased during both treatment times in the β-GPA fed mice compared to control mice. Body mass, muscle mass, and muscle fiber size significantly decreased after β-GPA treatment, whereas muscle capillarity and BMR were significantly increased in β-GPA fed mice. NET significantly decreased in the 2-week treatment, but was not significantly different in the 6-week treatment. HET significantly decreased in 2-week treatment, but in contrast to NET, significantly increased in the 6-week-treated mice compared to control mice. We conclude that β-GPA induces a cellular energetic response in skeletal muscle similar to that of chronic environmental hypoxia, and this energetic perturbation leads to elevated BMR and increased hypoxic exercise capacity in the absence of hypoxic acclimation.


Localization of visual targets during optokinetic eye movements.
We investigated localization of brief visual targets during reflexive eye movements (optokinetic nystagmus). Subjects mislocalized these targets in the direction of the slow eye movement. This error decreased shortly before a saccade and temporarily increased afterwards. The pattern of mislocalization differs markedly from mislocalization during voluntary eye movements in the presence of visual references, but (spatially) resembles mislocalization during voluntary eye movements in darkness. Because neither reflexive eye movements nor voluntary eye movements in darkness have explicit (visual) goals, these data support the view that visual goals support perceptual stability as an important link between pre- and post-saccadic scenes.


Systemic sclerosis in childhood.
Juvenile systemic sclerosis (jSSc) is a rare disease of childhood, and the amount of published data is limited. It appears that its clinical presentation differs from adult disease and the limited form affects only very few children. The organ involvement pattern differs also from the adult form. Prognosis seems to be better with a 5-yr survival of 95% of the jSSc patients. The validation of the outcome measures for children with jSSc is currently in progress. Regarding effective treatment, there are no paediatric data and the paediatric rheumatologist needs to rely on the experiences in adult disease.


Antithrombotic Therapy After Venous Interventions: AJR Expert Panel Narrative Review.
Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, postprocedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data and incomplete mechanistic understanding of the critical factors driving long-term patency. Postinterventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis because of procedural or patient factors. The added benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual- and/or triple-agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of nonthrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single-agent or multiagent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize postprocedural anti-thrombotic therapy in patients receiving venous interventions.


ANGIOGRAPHIC FINDINGS OF RANIBIZUMAB-RESISTANT POLYPOIDAL CHOROIDAL VASCULOPATHY AFTER SWITCHING TO A TREAT-AND-EXTEND REGIMEN WITH INTRAVITREAL AFLIBERCEPT.
The aim of this study was to study the angiopathic findings of ranibizumab-resistant polypoidal choroidal vasculopathy after switching to a treat-and-extend regimen with intravitreal aflibercept. The authors retrospectively reviewed 17 eyes of 17 Japanese patients with polypoidal choroidal vasculopathy (10 men and 7 women, age: 73.8 ± 7.4 years) who were treated with intravitreal aflibercept (2 mg/0.05 mL) injections from February 2013 to August 2014 at Tokyo University Hospital. All patients had switched to aflibercept because their polypoidal choroidal vasculopathy had been refractory to ranibizumab. The mean logMAR best-corrected visual acuity at baseline and after 12 months of therapy was 0.30 ± 0.29 (Snellen equivalent: 20/40) and 0.17 ± 0.26 (20/30) (paired t-test P < 0.001). Visual acuity remained stable in 5 cases (29%), deteriorated in 3 (18%), and improved in 9 (53%). Branching vascular networks persisted in all 17 eyes but shrank in 15 (88%). The mean lesion diameter was 3329 ± 1261 μm at baseline and 3180 ± 1247 μm after 12 months (P = 0.0002). A treat-and-extend regimen with intravitreal aflibercept for ranibizumab-resistant patients resulted in branching vascular network shrinkage over a 1-year period.


Clofibrate PPARα activation reduces oxidative stress and improves ultrastructure and ventricular hemodynamics in no-flow myocardial ischemia.
Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPARα stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.


The inflammasome mediates hyperoxia-induced alveolar cell permeability.
A hallmark of hyperoxic acute lung injury is the influx of inflammatory cells to lung tissue and the production of proinflammatory cytokines, such as IL-1beta; however, the mechanisms connecting hyperoxia and the inflammatory response to lung damage is not clear. The inflammasome protein complex activates caspase-1 to promote the processing and secretion of proinflammatory cytokines. We hypothesized that hyperoxia-induced K(+) efflux activates the inflammasome via the purinergic P2X7 receptor to cause inflammation and hyperoxic acute lung injury. To test this hypothesis, we characterized the expression and activation of inflammasome components in primary murine alveolar macrophages exposed to hyperoxia (95% oxygen and 5% CO(2)) in vitro, and in alveolar macrophages isolated from mice exposed to hyperoxia (100% oxygen). Our results showed that hyperoxia increased K(+) efflux, inflammasome formation, release of proinflammatory cytokines, and induction of caspase-1 and IL-1beta cleavage both in vitro and in vivo. The P2X7 agonist ATP enhanced hyperoxia-induced inflammasome activation, whereas the P2X7 antagonist, oxidized ATP, inhibited hyperoxia induced inflammasome activation. In addition, when ATP was scavenged with apyrase, hyperoxia-induced inflammasome activation was significantly decreased. Furthermore, short hairpin RNA silencing of inflammasome components abrogated hyperoxia-induced secretion of proinflammatory cytokines in vitro. These results suggest that hyperoxia induces K(+) efflux through the P2X7 receptor, leading to inflammasome activation and secretion of proinflammatory cytokines. These events would affect the permeability of the alveolar epithelium and ultimately lead to epithelial barrier dysfunction and cell death.


Radioimmunoassay for human beta interferon.
Pure human beta interferon (Hu IFN-beta) (formerly human fibroblast interferon) was used to raise antibodies in rabbits. Anti-IFN-beta immunoglobulins from rabbit serum were purified by IFN-beta affinity chromatography and were used in the development of a sandwich-type radioimmunoassay for Hu IFN-beta. This radioimmunoassay consisted of (i) incubating Hu IFN-beta with anti-IFN-beta immunoglobulins immobilized on Sepharose 4B beads and (ii) incubating the resulting solid-phase IFN antibody complex with 125I-labeled anti-Hu IFN-beta immunoglobulins. The amount of 125I-labeled anti-Hu IFN-beta bound to the complex was linearly proportional to the amount of antiviral activity present in the complex from 0 to 500 U of standard IFN-beta per ml; 1 U of antiviral activity was equivalent to about 40 cpm of 125I-labeled anti-IFN immunoglobulins in the radioimmunoassay. The results of the radioimmunoassay were not influenced by the protein content of the IFN sample assayed, and the degree of intraassay variability was low; coefficients of variability were 9.4% at 5 U/ml and 1.1% at 500 U/ml. Thus, compared with the traditional antiviral assay for IFN, this radioimmunoassay was equally sensitive and more precise. In addition, it was highly specific for Hu IFN-beta and took only 5 h to complete.


Using heat to kill SARS-CoV-2.
The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS-CoV-2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.


Assessment of Bilateral Thoracic Loading on the Near-Side Occupant Due to Occupant-to-Occupant Interaction in Vehicle Crash Tests.
This study aims, by means of the WorldSID 50th percentile male, to evaluate thoracic loading and injury risk to the near-side occupant due to occupant-to-occupant interaction in combination with loading from an intruding structure. Nine vehicle crash tests were performed with a 50th percentile WorldSID male dummy in the near-side (adjacent to the intruding structure) seat and a THOR or ES2 dummy in the far-side (opposite the intruding structure) seat. The near-side seated WorldSID was equipped with 6 + 6 IR-Traccs (LH and RH) in the thorax/abdomen enabling measurement of bilateral deflection. To differentiate deflection caused by the intrusion, and the deflection caused by the neighboring occupant, time history curves were analyzed. The crash tests were performed with different modern vehicles, equipped with thorax side airbags and inflatable curtains, ranging from a compact car to a large sedan, and in different loading conditions such as car-to-car, barrier, and pole tests. Lateral delta V based on vehicle tunnel acceleration and maximum residual intrusion at occupant position were used as a measurement of crash severity to compare injury measurements. In the 9 vehicle crash tests, thoracic loading, induced by the intruding structure as well as from the far-side occupant, varied due to the size and structural performance of the car as well as the severity of the crash. Peak deflection on the thoracic outboard side occurred during the first 50 ms of the event. Between 70 to 150 ms loading induced by the neighboring occupant occurred and resulted in an inboard-side peak deflection and viscous criterion. In the tests where the target vehicle lateral delta V was below 30 km/h and intrusion less than 200 mm, deflections were low on both the outboard (20-40 mm) and inboard side (10-15 mm). At higher crash severities, delta V 35 km/h and above as well as intrusions larger than 350 mm, the inboard deflections (caused by interaction to the far-side occupant) were of the same magnitude or even higher (30-70 mm) than the outboard deflections (30-50 mm). A WorldSID 50th percentile male equipped with bilateral IR-Traccs can detect loading to the thorax from a neighboring occupant making injury risk assessment feasible for this type of loading. At crash severities resulting in a delta V above 35 km/h and intrusions larger than 350 mm, both the inboard deflection and VC resulted in high risks of Abbreviated Injury Scale (AIS) 3+ injury, especially for a senior occupant.


Partial characterization of the sialic acid-free forms of alpha-1-acid glycoprotein from human plasma.
Some of the properties of sialic acid-free alpha(1)-acid glycoprotein prepared by mild acid hydrolysis (pH1.6 at 80 degrees for 1hr.) were compared with those of neuraminidasetreated alpha(1)-acid glycoprotein. Chemically, the former contained less fucose (15%) and amide (2%) residues. Physicochemically, it had undergone certain changes primarily pertaining to the secondary structure, so that the specific optical rotation was more negative than that of the latter. A further expression of this change is probably the difference in the pH range of the resolution into two bands on electrophoresis. The resolution of the glycoprotein prepared by mild acid hydrolysis seems to be extended to more acidic pH values both by starch-gel and free moving-boundary electrophoresis. On ultracentrifugation both preparations appeared homogeneous and sedimented with a rate of 3s. Removal of sialyl residues at different pH values, in the range 1-7, showed that 2moles of sialic acid/mole of protein are very strongly bound. The two variants of alpha(1)-acid glycoprotein were isolated from pooled sialic acid-free alpha(1)-acid glycoprotein by preparative starch-gel electrophoresis and from selected blood of normal adults by fractionation by solubility and chromatography. Ultracentrifugal and starch-gel electrophoretic analyses at pH5, with incubation times of 1 or 24hr., demonstrated that no dissociation-association equilibrium (constant sedimentation coefficient and molecular weight) or isomerization (constant apparent electrophoretic mobilities) exist between the two variants. Therefore these variants are not sub-units of native alpha(1)-acid glycoprotein but represent modifications of naturally occurring proteins. Further, it was shown that the difference in the electrophoretic mobilities between the two variants was not due to any difference in amide content. Immunochemically, the two variants share the same determinants.


New flavonoids from the Saudi Arabian plant Retama raetam which stimulates secretion of insulin and inhibits α-glucosidase.
Retama raetam is a bush which is a member of the family Fabaceae. It is used traditionally in North Africa and Saudi Arabia for the treatment of diabetes. Several flavonoids and alkaloids are already known from this plant. Chromatographic fractionation and purification led to the isolation of three new derivatives of prenylated flavones, retamasin C-E, and four new derivatives of prenylated isoflavones, retamasin F-I, in addition to two isoflavones which have not been previously reported in this plant. Particularly interesting structures included isoflavones containing 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine and 3a,8b-dihydro-7-hydroxyfuro[3,2-b]benzo[2,1-d]furan units, both of which are new amongst natural product flavonoids. Five new examples (two flavones and three isoflavones) strongly enhanced the glucose-triggered release of insulin by murine pancreatic islets and one isoflavone was a potent inhibitor of α-glucosidase. This study may rationalise the traditional medicinal use of R. raetam and provide new leads for drug design in the treatment of diabetes.


Seroma Rates Are Not Increased When Combining Liposuction With Progressive Tension Suture Abdominoplasty: A Retrospective Cohort Study of 619 Patients.
Several studies have demonstrated that progressive tension sutures (PTS) reduce seroma. Many fear that adding liposuction to abdominoplasty will increase seroma rates and avoid drainless abdominoplasty when performing concomitant liposuction. We sought to identify whether liposuction increases seroma in PTS and non-PTS abdominoplasty. In this retrospective study, 619 patients underwent abdominoplasty between 2009 and 2017, of which 299 patients had drainless abdominoplasty with PTS and 320 had drain-based abdominoplasty. We compared complications among PTS patients with and without liposuction and among drain-based abdominoplasty patients with and without liposuction. Demographics were similar between PTS and drain patients and between liposuction and nonliposuction PTS. Mean liposuction volume with PTS was 1592 ± 1048 mL. Seroma in the PTS group was found to be 2.6%, which is consistent with previous data. PTS without liposuction had a rate of seroma of 6.67% compared to a rate of 2.2% with liposuction; these rates were not significantly different (P = 0.20). A total of 207 patients had drain-based abdominoplasty with liposuction, and 113 had it without liposuction. Seroma with liposuction was 9.17% and without liposuction was 6.19%, although these differences were not significant (P = 0.52). PTS lipoabdominoplasty had less seroma compared with drain-based lipoabdominoplasty (P = 0.01). Liposuction was performed in 80% of the patients, and patients with lipoabdominoplasty were not at a higher risk of seroma, in the drain group or the PTS group. More patients may allow validation that liposuction may actually be protective with PTS. Regardless, there is no increase in seroma with the addition of liposuction to PTS drainless abdominoplasty.


Toll-like receptor 9 acts at an early stage in host defence against pneumococcal infection.
Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9-deficient mice have been shown to be more sensitive than wild-type mice to viral, but not to bacterial infections. Here, we show that mice deficient in TLR9 but not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a respiratory tract bacterial infection caused by Streptococcus pneumoniae. Intranasal challenge studies revealed that TLR9 plays a protective role in the lungs at an early stage of infection prior to the entry of circulating inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of phagocytic activity from resident macrophages leading to an early clearance of bacteria from the lower respiratory tract.


Effects of Honey on Oral Mucositis among Pediatric Cancer Patients Undergoing Chemo/Radiotherapy Treatment at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia.
One of the most common complications of cancer chemotherapy is oral mucositis. This study evaluates the therapeutic effects of honey with the focus on grade III and IV oral mucositis, reduction of bacterial and fungal infections, duration of episodes of oral mucositis, and body weight in pediatric leukemic patients undergoing chemo/radiotherapy. This is an open labeled randomized controlled study conducted at our hospital on 40 pediatric cancer patients undergoing chemo/radiotherapy. All the 40 patients included in this study experienced a sum total of 390 episodes of fever and neutropenia associated with oral mucositis. A significant reduction of oral mucositis, associated Candida, and aerobic pathogenic bacterial infections was noted in patients in the honey treatment group. Also, there is a significant decrease in the duration of hospitalization for all those in the treatment group combined with a significant increase of body weight, delayed onset, and decreased severity of pain related to oral mucositis. Complications of oral mucositis can be tremendously reduced by the topical application of local Saudi honey and honey should be used as an integrative approach in prophylaxis and treatment of chemo/radiotherapy-induced oral mucositis in pediatric cancer patients. Further research is needed to elucidate and better understand the underlying mechanism.


Pharmacologic determinants of tobacco self-administration by humans.
Tobacco is a naturally occurring source of nicotine, which is a chemical of demonstrable abuse liability and dependence potential. All commonly used forms of tobacco result in the delivery of nicotine to the central nervous system (CNS), where its actions affect the probability of subsequent use. The role of nicotine as a determinant of patterns of tobacco self-administration and other tobacco-associated responses has frequently been confounded by the complexity of this form of drug self-administration, since the amount of nicotine delivered to the CNS is not a simple function of the amount of tobacco consumed. The present paper is a summary of data which indicate that nicotine administration and withdrawal are determinants of tobacco ingestion. Recent data that are reviewed include those which indicate that the following effects of nicotine bear an orderly relation to the dose administered: (1) reduction of cigarette smoking, (2) production of discriminative effects, and (3) blockade of tobacco withdrawal symptoms. A secondary intent of the present paper is to describe aspects of tobacco dependence which are relevant to the appreciation of the subsequent papers appearing in this series of eight.


Multiple enzymes related to differentiation of lymphocyte subpopulations in man.
We studied the relation of various enzymes to subpopulations of lymphocytes in man. T cell-rich fractions were separated with a nylon column from mononuclear cells in the buffy coat. Comparing the enzymatic profiles of the two fractions, we found that the difference between the two groups came from the dominancy of B cells and/or macrophages in the former fraction, and from that of T cells in the latter. The enzymes characterizing T cells included N-Ac-beta-D-glucosaminidase (GlcNAc-ase), prolyl endopeptidase (Post-Pro-Enz), and dipeptidyl aminopeptidase IV (DAP-IV), whereas those characterizing B cells and/or macrophages include poly(ADP-ribose) synthetase, leucine aminopeptidase (Leu-AP), AP-B, cathepsin B, sialidase, and AP-A. Inhibitors of these enzymes may lead to modification of the function of T and B cells.


Kinetics of wheat flour water uptake.
The kinetics of wheat flour water uptake at 15, 25, 35 and 45 degrees C and different relative humidities from 43.2 to 85.9 was investigated. The water uptake curves obtained were well described by the first-order kinetics equation. A suitable general empirical model was found that includes the effect of temperature and relative humidity.


Probiotic Characteristics of Lactobacillus curvatus DN317, a Strain Isolated from Chicken Ceca.
The probiotic characteristics of Lactobacillus curvatus DN317, a strain isolated from chicken ceca, were evaluated. This strain was selected for study from the isolated Lactobacillus strains because it has specific anti-microbial activity against Campylobacter jejuni ATCC 33560, Camp. jejuni NCTC 11168, Listeria monocytogenes ATCC 7644, and Bacillus subtilis ATCC 8633. Lact. curvatus DN317 showed an auto-aggregation percentage of 72% and presented the highest co-aggregation with Lact. monocytogenes ATCC 7644 (68%) compared to B. subtilis ATCC 8633 (45%), Camp. jejuni ATCC 33560 (36%), and Camp. jejuni NCTC 11168 (35%). The data revealed that Lact. curvatus DN317 could survive at 0.25% bile, maintain viability at pH 2.5 for 30 min, produce biosurfactants, and adhere to Caco-2 cells. Quantification of IL-6, IL-8, IL-10, and β-defensin 2 levels shows that Lact. curvatus DN317 induces an increase in IL-8 and β-defensin 2 secretion, while the levels of IL-6 and IL-10 do not change. Lact. curvatus DN317 showed high levels of esterase and cysteine arylamidase activities (5); moderate levels of esterase lipase, β-galactosidase, and α-galactosidase activities (4, 3); and weak levels of leucine arylamidase, valine arylamidase, and acid phosphatase activity (1). Various activities were obtained of α-chymotrypsin, β-glucuronidase, β-glucosidase, and N-acetyl-β-glucosaminidase, which have been associated with intestinal diseases. Lact. curvatus DN317 lowered the cholesterol level in MRS with and without bile. Antibiotic susceptibility tests indicated that DN317 was sensitive to ampicillin, gentamicin, kanamycin, streptomycin, tetracycline, clindamycin, erythromycin, and vancomycin but was resistant to chloramphenicol and ciprofloxacin. These results suggest that Lact. curvatus DN317 could potentially function as a probiotic.


Active Solvent Modulation: A Valve-Based Approach To Improve Separation Compatibility in Two-Dimensional Liquid Chromatography.
Two-dimensional liquid chromatography (2D-LC) is increasingly being viewed as a viable tool for solving difficult separation problems, ranging from targeted separations of structurally similar molecules to untargeted separations of highly complex mixtures. In spite of this performance potential, though, many users find method development challenging and most frequently cite the "incompatibility" between the solvent systems used in the first and second dimensions as a major obstacle. This solvent strength related incompatibility can lead to severe peak distortion and loss of resolution and sensitivity in the second dimension. In this paper, we describe a novel approach to address the incompatibility problem, which we refer to as Active Solvent Modulation (ASM). This valve-based approach enables dilution of 1D effluent with weak solvent prior to transfer to the 2D column but without the need for additional instrument hardware. ASM is related to the concept we refer to as Fixed Solvent Modulation (FSM), with the important difference being that ASM allows toggling of the diluent stream during each 2D separation cycle. In this work, we show that ASM eliminates the major drawbacks of FSM including complex elution solvent profiles, baseline disturbances, and slow 2D re-equilibration and demonstrate improvements in 2D separation quality using both simple small molecule probes and degradants of heat-treated bovine insulin as case studies. We believe that ASM will significantly ease method development for 2D-LC, providing a path to practical methods that involve both highly complementary 1D and 2D separations and sensitive detection.


Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation.
Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2-related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis.