Effects of dofetilide on cardiovascular tissues from normo- and hypertensive rats.
The aim was to test whether dofetilide has some potential for use in the treatment of heart failure. Dofetilide at < or = 3 x 10(-5) M had no effect on the quiescent Wistar Kyoto (WKY) rat aorta, mesenteric and intralobar arteries, or the spontaneous contractions of the WKY rat portal vein. Dofetilide at 10(-6) to 3 x 10(-5) M relaxed the KCl-contracted aorta. Dofetilide at 10(-9)-10(-7) M augmented the force of contraction of leftventricle strips from 12- and 18-month-old WKY rats at 2 Hz. Spontaneously hypertensive rats (SHRs) at 12 and 17-21 months of age are models of cardiac hypertrophy and failure, respectively. The augmentation of force at 2 Hz with dofetilide was similar on 12- and 18-month-old WKY rats and 12-month-old SHRs but reduced on the 18-month-old SHR left ventricle. At a higher more physiological frequency, 4 Hz, the threshold concentration of dofetilide required to augment the force responses of 21-month-old SHR left ventricles was markedly increased and the maximum augmenting effect was decreased. Dofetilide at 10(-7)-10(-5) M reduced the rate of the 17-month-old WKY rat right atrium, and had a similar effect on age-matched SHR right atrium. In summary, dofetilide is a positive inotrope and negative chronotrope in the rat. However, as the positive inotropic effect is not observed with clinically relevant concentrations at a physiological rate in heart failure, dofetilide is unlikely to be useful as a positive inotrope in the treatment of heart failure.


Applications of a new carbonated calcium phosphate bone cement: early experience in pediatric and adult craniofacial reconstruction.
Hydroxyapatite cements have recently been employed as bone substitutes in craniofacial reconstruction. They are easily applied, nonresorbable, available in unlimited quantity, and eliminate donor-site morbidity. Norian CRS (craniofacial repair system) is a new carbonated calcium phosphate paste that is unique in that it more closely resembles bone than do traditional hydroxyapatite pastes. Norian is a low-order crystalline apatite soluble at a low pH, facilitating its resorption and replacement by host bone. The cement was first used for craniofacial surgery in North America at the Children's Hospital of Philadelphia. This report presents the authors' experience with this bone substitute in both pediatric and adult craniofacial reconstruction. Sixteen adult and pediatric patients underwent craniofacial reconstruction involving the use of carbonated calcium phosphate paste for correction of defects that required from 5 to 110 g of carbonated calcium phosphate paste (mean, 28.5 g). The patients were all followed for a minimum of 14 months. Minor complications included one case of infection and two cases involving cement microfragmentation. In the authors' experience, carbonated calcium phosphate paste has proved to be an excellent alloplastic material for osseous augmentation and reconstruction in the craniofacial skeleton. Few problems were encountered using this material; no significant morbidity was encountered. Although this material seems to be promising as a bone substitute, further follow-up will be necessary to evaluate its potential role in craniofacial surgery.


Action of certain tropine esters on voltage-clamped lobster axon.
Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClphiA), which differs from TPTA only by the substitution of a p-Cl for a p-CH(3) group on the benzene ring, had a negligible effect on axonal excitability.


Histamine, 5-HT & hyaluronidase in the venom of the scorpion Lychas laevifrons (Pock).
Factors involved in the pathophysiological changes such as severe pain, burning sensation, redness, swelling and edema in case of the scorpion L. laevifrons were investigated. The presence of pain-producing autacoids histamine 2.1 +/- 0.18 micrograms/mg and 5-HT 0.23 +/- 0.1 micrograms/ml was confirmed by thin layer chromatography and bioassay. Histamine releasing substance was detected in vitro in the chopped guineapig lung. Venom also contained hyaluronidase 5 x 10(-4) N-acetyl-D-glucosamine released/h/mg, which facilitates spread of the toxic principles in the tissues. It is concluded that histamine, 5-HT, histamine-releasing factor and hyaluronidase are partly involved in the pathophysiological changes induced by the venom. It is suggested that mepyramine and cyproheptadine may prove useful in the management of scorpion envenomation.


Minimax Estimation of Functionals of Discrete Distributions.
We propose a general methodology for the construction and analysis of essentially minimax estimators for a wide class of functionals of finite dimensional parameters, and elaborate on the case of discrete distributions, where the support size S is unknown and may be comparable with or even much larger than the number of observations n. We treat the respective regions where the functional is nonsmooth and smooth separately. In the nonsmooth regime, we apply an unbiased estimator for the best polynomial approximation of the functional whereas, in the smooth regime, we apply a bias-corrected version of the maximum likelihood estimator (MLE). We illustrate the merit of this approach by thoroughly analyzing the performance of the resulting schemes for estimating two important information measures: 1) the entropy [Formula: see text] and 2) [Formula: see text], α > 0. We obtain the minimax L2 rates for estimating these functionals. In particular, we demonstrate that our estimator achieves the optimal sample complexity n ≍ S/ln S for entropy estimation. We also demonstrate that the sample complexity for estimating Fα (P), 0 < α < 1, is n ≍ S1/α /ln S, which can be achieved by our estimator but not the MLE. For 1 < α < 3/2, we show the minimax L2 rate for estimating Fα (P) is (n ln n)-2(α-1) for infinite support size, while the maximum L2 rate for the MLE is n-2(α-1). For all the above cases, the behavior of the minimax rate-optimal estimators with n samples is essentially that of the MLE (plug-in rule) with n ln n samples, which we term "effective sample size enlargement." We highlight the practical advantages of our schemes for the estimation of entropy and mutual information. We compare our performance with various existing approaches, and demonstrate that our approach reduces running time and boosts the accuracy. Moreover, we show that the minimax rate-optimal mutual information estimator yielded by our framework leads to significant performance boosts over the Chow-Liu algorithm in learning graphical models. The wide use of information measure estimation suggests that the insights and estimators obtained in this paper could be broadly applicable.


Trends in childhood injury mortality in a developing country: United Arab Emirates.
To describe the epidemiology of a leading cause of childhood mortality in Al-Ain, United Arab Emirates (UAE)--injury. To examine trends across types of injury, as well as the mechanisms of injury leading to death, by age groups, gender, citizenship, and explore mortality rates and make global comparisons. This is a retrospective, descriptive, statistical analysis of unlinked hospital data. Al-Ain and Tawam Hospitals, and Preventive Medicine Department, Al-Ain, United Arab Emirates. All cases that met the conditions established for the study: fell within the age group of 0 to 14 years, suffered from injuries, and were admitted to either Al-Ain or Tawam hospitals and subsequently died within the studied time period of 1 January 1995 to 31 December 2004. A total of 7204 deaths were reported in children below 15 years during the studied time period. Of these cases, 2150 children died due to injury, comprising 29.8% of total deaths. Further analysis showed that road traffic injuries were the most frequent cause of injury leading to death (68.3%). Overall injury death rates were higher in non-citizens (54.5%) than in citizens (45.5%); and males had a higher incidence, specifically a 2.1:1 ratio, than females. Children 5 to 14 years had the highest frequency of injury deaths. Overall, injury mortality rates exhibited a decreasing, though fluctuating, trend during the studied period at a rate that is comparable to those in other developed nations such as New Zealand and USA. The present study reveals that the burden of injury deaths among children below 15 years is significant; and injuries exist in every form and affect every age group, and gender. The high burden of injuries on children in the UAE demands the attention of the health community, including policy makers. An understanding of the trends such as those presented in this study, for instance that injuries from road traffic are prominent, will assist in the development of interventions to address this growing concern. Furthermore, similarities in rates of UAE with other developed countries signify the potential for appropriate responses to lower the burden of injuries on children in the future.


Investigation of factors affecting sodium alginate fouling mechanisms in a microfiltration process under non-constant-flux and non-constant-pressure conditions.
Variations in transmembrane pressure and permeate flux are closely related to membrane fouling. In this study, a laboratory-scale submerged microfiltration system was used to investigate the influence of sodium alginate (SA) concentration and peristaltic pump rotation speed on the fouling under the conditions of (1) the same driving force and non-aerated-PAC, (2) different driving forces and non-aerated-PAC, and (3) different driving forces and aerated-PAC. The results showed that the normalized transmembrane pressure (TMP') increased linearly with decreasing normalized permeate flux (J') during the early microfiltration stage regardless of the operating conditions, indicating that the SA microfiltration process controlled by the peristaltic pump was non-constant-flux and non-constant-pressure. The latter filtration stage was considered constant-pressure filtration when 200-1,200 mg/L of SA was filtrated at the same rotation speed. During filtration of 800 mg/L of SA under the non-aerated-PAC condition, the later filtration stage was considered constant-pressure filtration when the peristaltic pump rotated at slower speeds of 15 and 30 rpm. This approached constant-flux filtration when the peristaltic pump rotated at faster speeds of 60 and 90 rpm, and PAC-aeration scouring was an effective measure for mitigating membrane fouling by SA.


Structurally diverse indole alkaloids with cytotoxicity from Lonicera Japonica-associated endophytic fungus Penicillium ochrochloron YT2022-65.
Natural products, especially fungal secondary metabolites, have been served as valuable sources of drug leads in pharmaceutical industry. Medicinal plants-associated endophytic fungi possess a well-developed secondary metabolism. In this study, chemical investigation on Penicillium ochrochloron YT2022-65, an endophytic fungus associated with Lonicera Japonica, led to the isolation of six structurally diversified indole alkaloids, including a new one, namely peniochroloid A (1), as well as five previously reported alkaloids, flavonoid B (2), brocaeloid C (3), isoroquefortine C (4), roquefortine C (5), and dihydrocarneamide A (6). Their structures, including the absolute configuration of 1, were determined by a combined analysis of HRESIMS, NMR spectroscopic data, and calculation of the optical rotation. Their cytotoxicity against A549, HepG2, MCF-7, and THP-1 cell lines were evaluated in vitro. The new compound 1 was found to possess considerable cytotoxicity against MCF-7 and THP-1 cell lines with IC50 values of 10.2 and 11.0 μM, respectively.


Lupus nephritis: correlation of immunohistochemical expression of C4d, CD163-positive M2c-like macrophages and Foxp3-expressing regulatory T cells with disease activity and chronicity.
C4d, which is a serum complement cleavage product of the activated complement component C4, was found to be an accurate indicator of lupus activity compared to complement levels. Recently, macrophages have been considered to be pivotal members in the pathogenesis of lupus nephritis (LN). M2c-like macrophages have anti-inflammatory functions and promote fibrosis. Multiple studies have detected that LN is associated with an imbalance between the regulatory T cell (Treg) population and the inflammatory T helper subtypes. We evaluated and scored the immunohistochemical expression of C4d, CD163-positive M2C-macrophages and Foxp3-expressing Tregs in 53 renal biopsies of LN. Their expression was scored and correlated with clinical and histological disease activity and chronicity. Class IV was the most prevalent class (50.9%), followed by class III (17%). PTC-C4d intensity score, CD163% of positive M2c macrophages and FOXP3% of positive Tregs were significantly correlated with chronicity index (rs = 0.292, p = 0.034; rs = 0.407, p = 0.003; and rs = 0.296, p = 0.031, respectively). Also, FOXP3% of positive Tregs was significantly correlated with LN class (rs = 0.31, p = 0.024). C4d-PTC, CD163-positive M2c macrophages and FOXP3-positive Tregs are markers that significantly correlated with chronicity in LN. Further studies are needed to evaluate their prognostic value.


Surface self-concentrating amphiphilic quaternary ammonium biocides as coating additives.
A variety of amphiphilic quaternary dimethylammonium compounds bearing n-alkyl and oxyethylene groups have been designed and synthesized as antimicrobial additives for use in self-decontaminating surfaces. The effectiveness of these additives stems from a unique ability to self-concentrate at the air-polymer interface without the incorporation of exotic perfluorinated or polymeric functionalities. X-ray photoelectron spectroscopy analysis reveals surface enrichment as high as 18-fold, providing a 7-log reduction of both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The migration to the surface is a consequence of the hydrophobicity of the additive within the hydrophilic polyurethane resin, over which an unprecedented level of control can be exerted by altering the lengths of the n-alkyl and oxyethylene groups. Thus, for the first time, specific surface and bulk coating concentrations can be achieved as desired using a single class of antimicrobial additives.


Giant spontaneous herniation of the post-pneumonectomy cavity.
Following a pneumonectomy, excessive mediastinal shift can cause rare complications involving the post-pneumonectomy cavity, which can become the seat of herniation of the residual lung and of the heart. We herein report an even more rare event, entailing an impressive herniation of the actual entire post-pneumonectomy cavity through an intercostal space, which developed spontaneously nearly 3 years after surgery. Surgical excision of the hernia sac and repair of the defect with polypropylene mesh provided adequate treatment and good cosmetic results. Postoperative recovery was uneventful and no signs of recurrence have been observed.


Why do symptomatic patients delay obtaining care for tuberculosis?
The resurgence of tuberculosis (TB) has coincided with deteriorating access to care for high-risk populations. We sought to determine what perceived access barriers delayed symptomatic TB patients from obtaining care. In order to do this, we conducted a survey in Los Angeles County, California, using a consecutive sample of patients with active TB as confirmed by the county TB control authority. The measures used in the study were a self-reported delay in seeking care of more than 60 d from symptom onset, a period sufficient to cause skin-test conversion in exposed contacts, and self-reported access barriers. The county TB registry provided supplementary clinical data. We found that one in five of the 248 symptomatic respondents (response rate: 60%) delayed obtaining care for > 60 d (mean = 74 d, SD = 216 d). During the delay, patients exposed an average of eight contacts. As compared with the rest of the sample, delay was more common in those who were unemployed (25% versus 14%), concerned about cost (27% versus 14%), anticipated prolonged waiting-room time (26% versus 14%), believed they could treat themselves (31% versus 14%), anticipated difficulty in getting an appointment (28% versus 16%), were uncertain about where to get care (33% versus 16%), and feared immigration authorities (47% versus 18%) (p < 0.05). Logistic regression revealed that uncertainty about where to get care, unemployment, and belief in the efficacy of self-treatment independently predicted delay > 60 d. Illness severity as measured by chest radiography, sputum smears, and symptoms had little impact on delay. We conclude that because access variables such as lack of employment and knowledge about where to obtain care were more closely associated with clinically significant delay than was severity of illness, these results raise concerns about the equity of access to care among TB patients. The results suggest that improving the availability of services for high-risk groups may substantially reduce TB patients' delay in obtaining care, and thus may limit the spread of the disease.


The Discovery of Reverse Transcriptase.
In 1970 the independent and simultaneous discovery of reverse transcriptase in retroviruses (then RNA tumor viruses) by David Baltimore and Howard Temin revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. In this historical review we describe the formulation of the controversial provirus hypothesis by Temin, which ultimately was proven by his discovery of reverse transcriptase in Rous sarcoma virus virions. Baltimore arrived at the same discovery through his studies on replication of RNA-containing viruses, starting with poliovirus and then moving to vesicular stomatitis virus, where he discovered a virion RNA polymerase. Subsequent studies of reverse transcriptase led to the elucidation of the mechanism of retrovirus replication, the discovery of oncogenes, the advent of molecular cloning, the search for human cancer viruses, and the discovery and treatment of HIV/AIDS.


Complex chromosomal changes in a primary squamous carcinoma of the parotid gland.
The chromosomal observations in a cultured primary epidermoid carcinoma of the parotid gland are reported. The tumour had a flat hyper-triploid mode with 7 recurrent wholly or partially identified marker types and 7-13 additional, mostly recurrent, markers, whose origin could not be clarified. There were also many recurring numerical deviations in most tumour cells. The picture was consistent with a neoplasma in an advanced stage of chromosomal progression. So far, 6q-markers with varying morphology are the only deviations found in most types of malignant salivary tumours and, in particular, in a high percentage of adenoid-cystic carcinomas. One possible explanation for these observations is the occurrence of one or more suppressor genes in 6q which may have relevance for malignant neoplasia in salivary gland tissues.


Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway.
Chronic inflammation is thought to be a determinant of the aging rate and longevity. Caloric restriction (CR) attenuates age-related increases in the systemic levels of several pro-inflammatory mediators, but the anti-inflammatory mechanisms of CR in the aging process remain unclear. Fisher 344 rats in a CR group were fed an amount of food corresponding to 60% of that fed to an ad libitum-fed (AL) group for 8 months. Biochemical analyses and renal pathological grading were used to analyze physiological status. Important signaling molecules in the Toll-like receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/NF-κB) pathway were also analyzed by western blotting, immunofluorescence and immunohistochemistry. 1) Compared with AL feeding, CR decreased aging-mediated increases in both biochemical marker levels and renal pathological grading. 2) Single immunoglobulin IL-1 (IL-1)-related receptor (SIGIRR) expression decreased with increasing age, but CR led to overexpression. 3) The expression of TLR4 was significantly higher in the CR group than in the AL group. 4) SIGIRR overexpression decreased the expression of the adaptor molecules myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6). 5) The levels of the inflammatory markers phospho-IκBα and phospho-NF-κB p65 decreased in the CR group. The inflammatory response might be alleviated by SIGIRR via blockade of the TLR4/NF-κB signaling pathway. Therefore, CR can decrease inflammation via SIGIRR overexpression, and SIGIRR might be a new target to delay aging.


Acinetobacter calcoaceticus bacteremia: analysis of 48 cases.
The medical records of 48 patients with Acinetobacter calcoaceticus bacteremia over a recent two-year period were reviewed retrospectively to determine the epidemiologic and clinical features. There were 34 males and 14 females with a median age of 51 years. Forty-six of the cases were hospital-acquired. The characteristics of these patients included residence in the intensive care unit, intubation and ventilatory support, preceding antibiotic therapy and intravascular catheterization. In vitro susceptibility testing for the isolated organisms revealed that 32% of these strains were resistant to gentamicin and 90% were aztreonam-resistant. Minocycline, amikacin, ceftazidime, ticarcillin, imipenem, and the new quinolones retained good activity. Although A. calcoaceticus causes septic pictures as do other aerobic Gram-negative bacilli and part of these isolates are multiple drug-resistant, the infection did not seem to be difficult to control. Twenty-six (54%) of these patients survived, including 9 patients without appropriate antimicrobial therapy initiated within 48 hours of blood sampling. The mortality was rarely due to bacteremia per se; most often, it resulted from the underlying diseases.


Enantiospecific Total Synthesis of the Highly Strained (-)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization.
A rare element of high strain in molecules of natural origin is a 1,2-trans fusion of 5-membered rings within a [3.3.0]-bicycle, a motif present in (-)-presilphiperfolan-8-ol. This molecule also possesses a 1,3-trans stereochemical arrangement of substituents on one of its 5-membered rings, a pattern shared by a number of other terpenes. Herein, we disclose the first total synthesis of this highly strained target in 13 steps. The key operation is a Pd-catalyzed tandem cyclization that directly establishes the requisite 1,3-trans stereochemical arrangement on one ring while concurrently setting the stage for the controlled generation of the highly strained 1,2-trans ring fusion of the final architecture.


Characterization of Three Novel Fatty Acid- and Retinoid-Binding Protein Genes (Ha-far-1, Ha-far-2 and Hf-far-1) from the Cereal Cyst Nematodes Heterodera avenae and H. filipjevi.
Heterodera avenae and H. filipjevi are major parasites of wheat, reducing production worldwide. Both are sedentary endoparasitic nematodes, and their development and parasitism depend strongly on nutrients obtained from hosts. Secreted fatty acid- and retinol-binding (FAR) proteins are nematode-specific lipid carrier proteins used for nutrient acquisition as well as suppression of plant defenses. In this study, we obtained three novel FAR genes Ha-far-1 (KU877266), Ha-far-2 (KU877267), Hf-far-1 (KU877268). Ha-far-1 and Ha-far-2 were cloned from H. avenae, encoding proteins of 191 and 280 amino acids with molecular masses about 17 and 30 kDa, respectively and sequence identity of 28%. Protein Blast in NCBI revealed that Ha-FAR-1 sequence is 78% similar to the Gp-FAR-1 protein from Globodera pallida, while Ha-FAR-2 is 30% similar to Rs-FAR-1 from Radopholus similis. Only one FAR protein Hf-FAR-1was identified in H. filipjevi; it had 96% sequence identity to Ha-FAR-1. The three proteins are alpha-helix-rich and contain the conserved domain of Gp-FAR-1, but Ha-FAR-2 had a remarkable peptide at the C-terminus which was random-coil-rich. Both Ha-FAR-1 and Hf-FAR-1 had casein kinase II phosphorylation sites, while Ha-FAR-2 had predicted N-glycosylation sites. Phylogenetic analysis showed that the three proteins clustered together, though Ha-FAR-1 and Hf-FAR-1 adjoined each other in a plant-parasitic nematode branch, but Ha-FAR-2 was distinct from the other proteins in the group. Fluorescence-based ligand binding analysis showed the three FAR proteins bound to a fluorescent fatty acid derivative and retinol and with dissociation constants similar to FARs from other species, though Ha-FAR-2 binding ability was weaker than that of the two others. In situ hybridization detected mRNAs of Ha-far-1 and Ha-far-2 in the hypodermis. The qRT-PCR results showed that the Ha-far-1and Ha-far-2 were expressed in all developmental stages; Ha-far-1 expressed 70 times more than Ha-far-2 in all stages. The highest expression level of Ha-far-1 was observed in fourth-stage juvenile (J4), whereas the highest expression level of Ha-far-2 occurred in second-stage juvenile (J2). In conclusion, we have identified two novel far genes from H. avenae and one from H. filipjevi and have provided further indication that nematode far genes are present in a variety of nematode species, where the FAR proteins share similar basic structure, expression pattern and biochemical activities.


Advancing host-directed therapy for tuberculosis.
Tuberculosis (TB) drug-development strategies, a wide range of candidate host-directed therapies (HDT)s-including new and repurposed drugs, biologics, and cellular therapies-have been proposed to accelerate eradication of infection and overcome the problems associated with current treatment regimens. By investigating the interaction between macrophages and the intracellular parasite Toxoplasma gondii (T. gondii), we uncovered that infection-induced signaling pathways suggest possibilities for the development of novel therapeutic modalities for TB that target the intracellular signaling pathways permitting the replication of Mycobacterium tuberculosis (MTB).


Epileptogenesis: can the science of epigenetics give us answers?
Epigenetic mechanisms are regulatory processes that control gene expression changes involved in multiple aspects of neuronal function, including central nervous system development, synaptic plasticity, and memory. Recent evidence indicates that dysregulation of epigenetic mechanisms occurs in several human epilepsy syndromes. Despite this discovery of a potential role for epigenetic mechanisms in epilepsy, few studies have fully explored their contribution to the process of epilepsy development known as epileptogenesis. The purpose of this article is to discuss recent findings suggesting that the process of epileptogenesis may alter the epigenetic landscape, affecting the gene expression patterns observed in epilepsy. Future studies focused on a better characterization of these aberrant epigenetic mechanisms hold the promise of revealing novel treatment options for the prevention and even the reversal of epilepsy.


Appropriate medical care for persons in detention.
The people who are in detention are screened by the Medical Officer of the Prison and if they are found to be unwell, these prisoners will be accommodated in the sickbay and medical treatment will be provided. If their sickness needs further investigations and management, they will be sent to the Government Hospital. If the prisoners are found to have infectious or contagious diseases, steps will be taken to prevent the spread of these diseases to other prisoners in the prison. Prisoners are given time to exercise to maintain good health and their clothing are regularly washed to make sure that they will not contract skin diseases, e.g. scabies, ringworm, etc. The Prison Department since 1989 has increasing numbers of HIV positive prisoners. The Department complies with this problem by sending staff for courses, lectures and seminars so that they will be able to handle these prisoners more efficiently in the prison. When these HIV/AIDS prisoners' condition turns bad, they are usually transferred to a Government Hospital. Another of the Prison Department's prominent medical problem among the prisoners is drug addiction. Staff trained with skill and techniques are counselors for the drug related prisoners. Realizing and in anticipation that the sickbays in the prisons are going to be full of HIV/AIDS prisoners and drug related prisoners, special attention will be given to more allocation to upgrade the sickbays in the prison. White attires will be provided to the sick prisoners in the sickbays so that they will look neat and clean. More doctors, medical assistants and nurses will be employed so that appropriate medical care or rather more appropriate medical care can be provided to the sick prisoners in the prisons. The Prison Department is in the process of privatizing medical care for prisoners in the prison and the Department is also trying to convert some prisons to be medical prisons so that adequate medical care can be given to the sick prisoners.


Residue 146 regulates prolactin receptor folding, basal activity and ligand-responsiveness: potential implications in breast tumorigenesis.
PRLR(I146L) is the first identified gain-of-function variant of the prolactin receptor (PRLR) that was proposed to be associated with benign breast tumorigenesis. Structural investigations suggested this hydrophobic core position in the extracellular D2 domain to be linked to receptor dimerization. Here, we used a mutational approach to address how the conservative I-to-L substitution induced constitutive activity. Using cell-based assays of different I146-PRLR variants in combination with spectroscopic/nuclear magnetic resonance analyses we found that chemical manipulation of position 146 profoundly altered folding, PRL-responsiveness, and ligand-independent activity of the receptor in a mutation-specific manner. Together, these data further add to the critical role of position 146, showing it to also be crucial to structural integrity thereby imposing on the biological PRLR properties. When stably introduced in MCF-7 (luminal) and MDA-MB231 (mesenchymal) breast cancer cells, the most potent of the PRL-insensitive mutants (PRLR(I146D)) had minimal impact on cell proliferation and cell differentiation status.


Music, emotion, and time perception: the influence of subjective emotional valence and arousal?
The present study used a temporal bisection task with short (<2 s) and long (>2 s) stimulus durations to investigate the effect on time estimation of several musical parameters associated with emotional changes in affective valence and arousal. In order to manipulate the positive and negative valence of music, Experiments 1 and 2 contrasted the effect of musical structure with pieces played normally and backwards, which were judged to be pleasant and unpleasant, respectively. This effect of valence was combined with a subjective arousal effect by changing the tempo of the musical pieces (fast vs. slow) (Experiment 1) or their instrumentation (orchestral vs. piano pieces). The musical pieces were indeed judged more arousing with a fast than with a slow tempo and with an orchestral than with a piano timbre. In Experiment 3, affective valence was also tested by contrasting the effect of tonal (pleasant) vs. atonal (unpleasant) versions of the same musical pieces. The results showed that the effect of tempo in music, associated with a subjective arousal effect, was the major factor that produced time distortions with time being judged longer for fast than for slow tempi. When the tempo was held constant, no significant effect of timbre on the time judgment was found although the orchestral music was judged to be more arousing than the piano music. Nevertheless, emotional valence did modulate the tempo effect on time perception, the pleasant music being judged shorter than the unpleasant music.


Mechanisms of fungal resistance: an overview.
The increased use of antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antifungal resistance from different angles. In this article we discuss antifungal susceptibility testing, the mode of action of antifungals and mechanisms of resistance. Antifungals are grouped into five groups on the basis of their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which bind to fungal membrane sterol, resulting in the formation of aqueous pores through which essential cytoplasmic materials leak out; allylamines, which block ergosterol biosynthesis, leading to accumulation of squalene (which is toxic to the cells); candins (inhibitors of the fungal cell wall), which function by inhibiting the synthesis of beta 1,3-glucan (the major structural polymer of the cell wall); and flucytosine, which inhibits macromolecular synthesis. Different mechanisms contribute to the resistance of antifungal agents. These mechanisms include modification of ERG11 gene at the molecular level (gene mutation, conversion and overexpression), over expression of specific drug efflux pumps, alteration in sterol biosynthesis, and reduction in the intracellular concentration of target enzymes. Approaches to prevent and control the emergence of antifungal resistance include prudent use of antifungals, treatment with the appropriate antifungal and conducting surveillance studies to determine the frequency of resistance.


kil-kor regulon of promiscuous plasmid RK2: structure, products, and regulation of two operons that constitute the kilE locus.
The kil-kor regulon of IncP plasmid RK2 is a complex regulatory network that includes genes for replication and conjugal transfer, as well as for several potentially host-lethal proteins encoded by the kilA, kilB, and kilC loci. While kilB is known to be involved in conjugal transfer, the functions of kilA and kilC are unknown. The coregulation of kilA and kilC with replication and transfer genes indicates a possible role in the maintenance or broad host range of RK2. In this work, we found that a fourth kil locus, designated kilE, is located in the kb 2.4 to 4.5 region of RK2 and is regulated as part of the kil-kor regulon. The cloned kilE locus cannot be maintained in Escherichia coli host cells, unless korA or korC is also present in trans to control its expression. The nucleotide sequence of the kilE region revealed two potential multicistronic operons. The kleA operon consists of two genes, kleA and kleB, predicted to encode polypeptide products with molecular masses of 8.7 and 7.6 kDa, respectively. The kleC operon contains four genes, kleC, kleD, kleE, and kleF, with predicted products of 9.2, 8.0, 12.2, and 11.3 kDa, respectively. To identify the polypeptide products, each gene was cloned downstream of the phage T7 phi 10 promoter and expressed in vivo in the presence of T7 RNA polymerase. A polypeptide product of the expected size was observed for all six kle genes. In addition, kleF expressed a second polypeptide of 6 kDa that most likely results from the use of a predicted internal translational start site. The kleA and kleC genes are each preceded by sequences resembling strong sigma 70 promoters. Primer extension analysis revealed that the putative kleA and kleC promoters are functional in E. coli and that transcription is initiated at the expected nucleotides. The abundance of transcripts initiated in vivo from both the kleA and kleC promoters was reduced in cells containing korA or korC. When korA and korC were present together, they appeared to act synergistically in reducing the level of transcripts from both promoters. The kleA and kleC promoter regions are highly homologous and contain two palindromic sequences (A and C) that are the predicted targets for KorA and KorC proteins. DNA binding studies showed that protein extracts from korA-containing E. coli cells specifically retarded the electrophoretic mobility of DNA fragments containing palindrome A. Extracts from korC-containing cells altered the mobility of DNA fragments containing palindrome C. These results show that KorA and KorC both act as repressors of the kleAand kleC promoters. In the absence of korA and korC, expression of the cloned kleA operon was lethal to E.coli cells, whereas the cloned kleC operon gave rise to slowly growing, unhealthy colonies. Both phenotypes depended on at least one structural gene in each operon, suggesting that the operons encode genes whose products interact with critical host functions required for normal growth and viability. Thus, the kilA, kilC, and kilE loci of RK2 constitute a cluster of at least 10 genes that are coregulated with the plasmid replication initiator and the conjugal transfer system. Their potential toxicity to the host cell indicates that RK2 is able to establish a variety of intimate plasmid-host interactions that may be important to its survival in nature.


The rhizosphere as a reservoir for opportunistic human pathogenic bacteria.
During the last years, the number of human infections caused by opportunistic pathogens has increased dramatically. One natural reservoir of opportunistic pathogens is the rhizosphere, the zone around roots that is influenced by the plant. Due to a high content of nutrients, this habitat is a 'microbial hot-spot', where bacterial abundances including those with strong antagonistic traits are enhanced. Various bacterial genera, including Burkholderia, Enterobacter, Herbaspirillum, Ochrobactrum, Pseudomonas, Ralstonia, Staphylococcus and Stenotrophomonas, contain root-associated strains that can encounter bivalent interactions with both plant and human hosts. Mechanisms responsible for colonization of the rhizosphere and antagonistic activity against plant pathogens are similar to those responsible for colonization of human organs and tissues, and pathogenicity. Multiple resistances against antibiotics are not only found with clinical strains but also with strains isolated from the rhizosphere. High competition, the occurrence of diverse antibiotics in the rhizosphere, and enhanced horizontal gene transfer rates in this microenvironment appear to contribute to the high levels of natural resistances. While opportunistic bacteria from the rhizosphere have some properties in common, each of these emerging pathogens has its own features, which are discussed in detail for Burkholderia, Ochrobactrum and Stenotrophomonas.


How does the novel T315L mutation of breakpoint cluster region-abelson (BCR-ABL) kinase confer resistance to ponatinib: a comparative molecular dynamics simulation study.
Acute lymphocytic leukemia (ALL) is one of the most dangerous types of leukemia, and about 40% of them is Philadelphia chromosome-positive acute lymphocytic leukemia (Ph + ALL). Ph + ALL is caused by the fusion of the breakpoint cluster region (BCR) and the Ableson (ABL) genes, named the BCR-ABL fused gene that codes for an autonomously active tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are among the first-line therapeutic agents for the treatment of Ph + ALL. Drug resistance are the major obstacle, limiting their clinical utility. The latest third-generation TKIs, ponatinib, can tackle most abnormal BCR-ABL kinases, including the T315I mutant that is resistant to first- and second-generations TKIs such as imatinib. However, drug resistance still emerges with the novel T315L mutation and the underlying mechanisms remain elusive. Here, using molecular dynamics (MD) simulations, we explored into the detailed interactions between ponatinib and BCR-ABL in the wild-type (WT), T315I, and T315L systems. The simulations revealed the significant conformational changes of ponatinib in its binding site due to the T315L mutation and the underlying structural mechanisms. Binding free energy analysis unveiled that the affinity of ponatinib to BCR-ABL decreased upon T315L mutation, which resulted in its unfavorable binding and drug resistance. Key residues responsible for the unfavored unbinding were also identified. This study elucidates the detailed mechanisms for the resistance of ponatinib in Ph + ALL triggered by the T315L mutation and will provide insights for future drug development and optimization.


Breast surgery in stage IV breast cancer: impact of staging and patient selection on overall survival.
Retrospective analyses suggest patients with stage IV breast cancer who undergo breast surgery have improved survival. We sought to determine whether surgery and other clinical and staging factors affected overall survival. We performed a review of our prospectively maintained database of patients who presented with stage IV breast cancer between 1998 and 2005. We compared survival between women who received therapeutic surgery to the breast (S) versus those who did not (NS). Of the 147 women who presented with stage IV breast carcinoma, 61 (41%) underwent mastectomy or lumpectomy. Median overall survival unadjusted was 3.52 years for S versus 2.36 years for NS (P = 0.093). ER and Her2neu status were positive predictors of survival (HR: 0.191 and 0.285 P < 0.0001); CNS and liver metastases were adverse predictors (HR: 2.05 and 1.59 P = 0.015 P = 0.059). On multivariate survival was significantly superior in the surgery group (HR: 0.47 P = 0.003 mean 4.13 years versus 2.36 years). In those undergoing surgery, 36 women were diagnosed with metastatic disease postoperatively and 25 preoperatively. These groups had median survival of 4.0 years and 2.4 years, respectively, comparable to those in the NS group (2.36 years, (P = 0.18). Breast surgery is associated with improved survival in stage IV breast cancer. However, in our experience, this benefit is only realized among patients operated on before diagnosis of metastatic disease and is likely a consequence of stage migration bias. While some women may warrant palliative surgery to the breast, it is unclear that such surgery otherwise improves clinical outcomes.


["Emergency measures"].
This article deals with the impact of health crisis on governance of public health. It tries to show that, in accordance with the thought of Michel Foucault, emergency measures issued during health crisis are akin to those issued during wartime.


Cyclosporiasis outbreak, Indonesia.
We describe an outbreak of Cyclospora cayetanensis infection among Dutch participants at a scientific meeting in September 2001 in Bogor, Indonesia. Fifty percent of the investigated participants were positive for C. cayetanensis. To our knowledge, this outbreak is the first caused by C. cayetanensis among susceptible persons in a disease-endemic area.


Exploring the role of urinary extracellular vesicles in kidney physiology, aging, and disease progression.
Extracellular vesicles (EVs), membranous vesicles present in all body fluids, are considered important messengers, carrying their information over long distance and modulating the gene expression profile of recipient cells. EVs collected in urine (uEVs) are mainly originated from the apical part of urogenital tract, following the urine flow. Moreover, bacterial-derived EVs are present within urine and may reflect the composition of microbiota. Consolidated evidence has established the involvement of uEVs in renal physiology, being responsible for glomerular and tubular cross talk and among different tubular segments. uEVs may also be involved in other physiological functions such as modulation of innate immunity, coagulation, or metabolic activities. Furthermore, it has been recently remonstrated that age, sex, endurance excise, and lifestyle may influence uEV composition and release, modifying their cargo. On the other hand, uEVs appear modulators of different urogenital pathological conditions, triggering disease progression. uEVs sustain fibrosis and inflammation processes, both involved in acute and chronic kidney diseases, aging, and stone formation. The molecular signature of uEVs collected from diseased patients can be of interest for understanding kidney physiopathology and for identifying diagnostic and prognostic biomarkers.


[Echographic study of the bladder neck and prostate region after Nd-Yag laser treatment].
The authors describe the ultrasonic images they obtained in the follow up of three groups of patients who were divided according to basic pathology and treated with Nd: Yag Laser with contact (CLAP) and side firing (VLAP) fibers. Next the great differences noted between the results achieved with ultrasonic investigation and those obtained with flowmeter controls and IPSS are presented. The authors discuss the possible causes of these dissonances and hypothesize a new way to evaluate cervico-urethral de-obstruction: no longer an anatomical technique but a functional one.


Blood pressure is associated with occult cardiovascular disease in prospectively studied Hodgkin lymphoma survivors after chest radiation.
The objectives of this study were to prospectively screen a cohort of asymptomatic long-term survivors of Hodgkin lymphoma (HL) treated with chest irradiation for occult cardiovascular disease (CVD), and correlate screen-detected disease with prospectively measured cardiovascular risk factors (CRFs). A total of 182 HL survivors treated with chest irradiation (median follow-up time 14.8 years) were enrolled and underwent prospective CRF measurement and resting and stress echocardiography to assess coronary artery disease (CAD)/valve disease and left ventricular systolic dysfunction (LVSD). Forty-seven (26%) patients had occult CAD/valve disease and/or LVSD. LVSD was not correlated with CRFs. Controlling for treatment factors, hypertension (odds ratio [OR] = 3.0) and elevated high-sensitivity C-reactive protein (hs-CRP) (OR = 2.7) increased the likelihood of occult CAD/valve disease. Risk of CAD/valve disease rose exponentially with increasing blood pressure (BP) values, even in the normal range. Our findings suggest that BP screening may be useful in determining those survivors at greatest risk for occult CVD.


[Restriction fragment length differences of genomic repetitive DNA from five sibling species of Anopheles hyrcanus group].
Genomic DNA were prepared from 5 sibling species of Anopheles hyrcanus group including An. sinensis (ASS), An. anthropophagus (ALA), An. liangshanensis (ALS), An. crawfordi (ACW) and An. xiaokuanus (AXK). High molecular weight DNA from each species were cut with three restriction endonucleases (Bgl II, Hae III and Pst I) and the DNA fragments analysed by agarose gel electrophoresis and ethidium bromide staining. Three enzymes (Bgl II, Hae III and Pst I) produced unique fragments in all sibling species tested. A diagnostic restriction fragment length of DNA from 5 sibling species of An. hyrcanus group may be derived from a single restriction enzyme pattern (i.e. Bgl II). The results demonstrated that the restriction fragment length differences of repetitive DNA could used as a tool to distinguish sibling species of An. hyrcanus group.


Comparison of trace mineral repletion strategies in feedlot steers to overcome diets containing high concentrations of sulfur and molybdenum.
To compare trace mineral (TM) repletion in feedlot steers after depletion by S and Mo, 72 Red Angus steers blocked by BW (253 ± 14 kg) were assigned (6 steers per pen, fed via GrowSafe bunks) to corn silage depletion diets (depletion, DEP) supplemented with NRC (1996) recommended concentrations of Cu, Mn, Se, and Zn (CON) or supplemented with 0.3% S (CaSO4), 2 mg of Mo/kg dry matter (DM), and no added Cu, Mn, Zn, or Se (antagonist, ANT). Three 62 d TM repletion strategies (repletion, REP) were applied within DEP diets on day 89: 1) Multimin90 injection (contains Cu, Mn, Se, Zn) and 100% of recommended Cu, Mn, Zn, and Se from inorganic sources (ITM), 2) saline injection and 150% of recommended TM from inorganic sources (ING), or 3) saline injection and 150% of recommended TM provided as 25% organic and 75% inorganic sources (BLEND). Subcutaneous injections were given at 1 mL/68 kg BW. Inorganic sources were Cu, Mn, and Zn SO4, and sodium selenite, and organic sources were Availa Cu, Mn and Zn, and SelPlex Se. Repletion period liver and blood were collected on day -10, 14, 28, and 42 and data were analyzed as a 2 × 3 factorial (n = 12 steers per treatment) using Proc Glimmix of SAS with plasma and liver analytes analyzed as repeated measures. Liver Cu, Se, and Mn were decreased (P < 0.01) by ANT during DEP. There were no DEP × REP × day interactions in liver TM (P ≥ 0.18). A DEP × day effect was noted for liver Cu (P < 0.01) and Mn (P = 0.07), where ANT Cu increased linearly from day 0 to day 42, CON Cu was slightly increased on day 14 and day 28, and ANT Mn was lesser than CON Mn on all days except day 42. There were REP × day effects on liver Cu (P < 0.01) and Se (P < 0.01) where status was improved by ITM by day 14, increased in BLEND by day 28, and not different by day 42. Liver Se concentrations were lesser (P < 0.01) in ANT vs. CON throughout repletion. Liver Zn was greater (P < 0.01) on day 0 than day 14, 28, and 42, and concentrations were greater on day 42 than day 28. Glutathione peroxidase activity tended to be lesser (P = 0.07) on day 14 relative to other days. Manganese superoxide dismutase activity was lesser (P < 0.01) on day 14 and 28 compared to day 0 and 42, and tended to be lesser (P = 0.06) in ANT than CON during repletion. Final body weight (BW) and average daily gain (ADG) were not affected by treatment (P ≥ 0.60), and ANT decreased dry matter intake (DMI) (P = 0.04) and improved G:F (P < 0.01) during repletion. All repletion strategies were effective at increasing TM status of steers, and ITM had the most rapid recovery of Cu and Se status, followed by BLEND, and ING.


A general framework of persistence strategies for biological systems helps explain domains of life.
The nature and cause of the division of organisms in superkingdoms is not fully understood. Assuming that environment shapes physiology, here we construct a novel theoretical framework that helps identify general patterns of organism persistence. This framework is based on Jacob von Uexküll's organism-centric view of the environment and James G. Miller's view of organisms as matter-energy-information processing molecular machines. Three concepts describe an organism's environmental niche: scope, umwelt, and gap. Scope denotes the entirety of environmental events and conditions to which the organism is exposed during its lifetime. Umwelt encompasses an organism's perception of these events. The gap is the organism's blind spot, the scope that is not covered by umwelt. These concepts bring organisms of different complexity to a common ecological denominator. Ecological and physiological data suggest organisms persist using three strategies: flexibility, robustness, and economy. All organisms use umwelt information to flexibly adapt to environmental change. They implement robustness against environmental perturbations within the gap generally through redundancy and reliability of internal constituents. Both flexibility and robustness improve survival. However, they also incur metabolic matter-energy processing costs, which otherwise could have been used for growth and reproduction. Lineages evolve unique tradeoff solutions among strategies in the space of what we call "a persistence triangle." Protein domain architecture and other evidence support the preferential use of flexibility and robustness properties. Archaea and Bacteria gravitate toward the triangle's economy vertex, with Archaea biased toward robustness. Eukarya trade economy for survivability. Protista occupy a saddle manifold separating akaryotes from multicellular organisms. Plants and the more flexible Fungi share an economic stratum, and Metazoa are locked in a positive feedback loop toward flexibility.


Prognostic factors at the time of renal retransplantation.
One hundred and eighty-two patients with a second cadaver (CD) transplant performed during 1969-80 showed similar patient and graft survival to that of 535 recipients of first CD grafts. Loss of the first graft after 12 months resulted in a significantly higher second graft survival (GS II) than loss in early acute rejection within three months, 71 per cent vs 34 per cent at one year (p less than 0.01). A high frequency of presensitised patients was observed (53%) which negatively influenced the GS II, at one year 55 per cent vs 40 per cent for patients without and with antibodies (p less than 0.01). A good HLA-A, B match and absence of antibodies positively influenced GS II. Blood transfusions prior to the first transplantation did not influence survival of the second graft.


[Modification of mucociliary clearance by a combination of theophylline with ambroxol and of ambroxol in monotherapy].
Influence on Mucociliary Clearance by a Theophylline-Ambroxol Combination and by Ambroxol in Monotherapy. In a controlled randomised double-blind study the influence of theophylline + ambroxol (TA) and ambroxol (A) on lung function and mucociliary clearance was investigated. 19 patients with chronic obstructive lung disease were treated after a 5-day wash-out period for 5 days with TA (700 mg theophylline, 60 mg ambroxol/d) or A (60 mg ambroxol/d), respectively. Measurements were done on the 5th and 10th day. Under the treatment with TA a marked improvement of lung function was observed. The mucociliary clearance improved under treatment with TA and A, with TA being significantly better compared with treatment group A.


Detection and Identification of the Invasive Sirex noctilio (Hymenoptera: Siricidae) Fungal Symbiont, Amylostereum areolatum (Russulales: Amylostereacea), in China and the Stimulating Effect of Insect Venom on Laccase Production by A. areolatum YQL03.
The Eurasian woodwasp Sirex noctilio F. was first detected in Daqing, Heilongjiang Province, in the northeast region of China in 2013. Here, we investigated the S. noctilio's fungal symbiont, Amylostereum areolatum, and insect venom produced in its acid (venom) gland. Overall, seven out of 10 fungal isolates obtained from the mycangia of 10 adult S. noctilio females in this study were identified as A. areolatum. The remaining three isolates were identified as Trichoderma viride, Verticillium dahlia, and Geosmithia pallida, which were probably contaminants that entered during the mycangia-spore extraction process. The enzyme activity bioassay showed that the level of laccase activity of A. areolatum YQL03 in liquid medium is prominently enhanced by insect venom, but was relatively low when venom was not available as an inducer. This study confirms the presence of A. areolatum in S. noctilio specimens from China. The putative heat-stable factors identified in S. noctilio venom may contribute novel information about the pathogenic mechanism of the S. noctilio-A. areolatum pine-killing pest complex on host trees.


The influence of low concentration of cypermethrin and deltamethrin on phyto- and zooplankton of surface waters.
Pyrethroids play an important role in modern agriculture but their use is not without risks to non-target organisms and habitats. They have high toxicity to a broad spectrum of aquatic organisms. The aim of the study was to investigate the effect of low concentration (0.02 μg l(-1)) of two widely used pyrethroids--cypermethrin and deltamethrin on phyto- and zooplankton. The acute bioassays were conducted using Chlorella vulgaris and Thamnocephalus platyurus. Then, the chronic bioassays were conducted using Chlorella vulgaris, Daphnia magna and Brachionus calycilforus. The 24h LC50 values for cypermethrin and deltamethrin to Thamnocephalus platyurus were 0.89 μg l(-1) and 1.51 μg l(-1), respectively. The 48h EC50 values for cypermethrin and deltamethrin to Brachionus calycilforus were 3.828 mg l(-1) and 8.425 mg l(-1), respectively. 13% growth inhibition of Chlorella vulgaris (statistically insignificant) after 14 days of exposure to deltamethrin as well as cypermethrin was observed.


Intralesional Lidocaine Anesthesia: A Novel Facilitated Anesthesia Technique for Ethanol Sclerotherapy of Venous Malformation.
The aim of this study was to describe a novel anesthesia, intralesional lidocaine anesthesia (ILA), for ethanol sclerotherapy of venous malformation and evaluate the efficacy and safety. A prospective study of 100 patients with venous malformations undergoing 100 sclerotherapy procedures with intralesional lidocaine anesthesia (ILA) was conducted. Pain was evaluated by numeric rating scale (NRS) immediately following the procedure. The grade of pain was classified by the NRS as no pain (0), mild (1-3), moderate (4-6), and severe (7-10). Local and systemic complications caused by lidocaine were recorded. The median injected volume of absolute ethanol and 0.25% lidocaine was 5.9 mL and 17.0 mL, respectively. In ILA group, 13 patients had no pain during the procedure, 42 patients had mild pain, 38 patients had moderate pain, and 7 patients had severe pain. The mean NRS scores of the whole ILA group were 3.2 (0-8). No local or systemic complications attributed to lidocaine were reported. In a limited series, intralesional lidocaine anethesia seems to be efficient and safe for use in pain management for ethanol sclerotherapy of venous malformation. This anesthesia technique may be a promising first approach for the ethanol sclerotherapy of venous malformations, as it is easy to handle and has minimal sequelae.


Targeting EGFR/HER2 heterodimerization with a novel anti-HER2 domain II/III antibody.
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2. Moreover, a structural conformation change was observed in HER2 in complex with 7C3. Interestingly, this novel anti-HER2 antibody exhibits efficacy in blocking HER2/EGFR heterodimerization and signaling. The results highlight the different function role of HER2 domains and the unique potential of 7C3 to inhibit the HER2/EGFR heterodimer, which may complement current anti-HER2 treatments.


Repeated traumatic experiences in eating disorders and their association with eating symptoms.
This study aimed to analyze the association between traumatic experiences (TEs) and eating symptoms and their severity in a healthy group (HG) of students and an eating disorder group (EDG). The HG (N=150) comprised first- and secondyear undergraduate psychology students, the EDG (N=150) day hospital patients. EDG patients were evaluated consecutively when they entered the Day Hospital Eating Disorder Unit. Information on TEs was collected via an ad hoc questionnaire, a semi-structured interview and the first part of The Dissociation Questionnaire (Part I). The Bulimic Investigatory Test Edinburgh was used to evaluate eating symptoms and their severity. Emotional abuse was the most frequent TE in both groups. In the EDG, TEs occurred more in patients with purging behavior (anorexia nervosa of the binge-eating/purging type, AN-P; and bulimia nervosa of the purging type, BN-P) than in those with AN-R (anorexia nervosa of the restricting type). In patients with purging behavior, TEs often begin in childhood and are repeated. When the severity of eating symptoms in patients with EDs who had suffered repeated TEs was compared with those who had suffered an isolated TE, a tendency towards greater severity of eating symptoms associated with TE repetition was observed. The results obtained with respect to the presence and type of TEs in EDs concurred with those of other studies. However, unlike other studies, we found high percentages of childhood TEs in ED subtypes with purging behavior. In these ED subtypes, TEs tended to be more repeated than in ED subtypes with restrictive behavior. Further studies are required to draw conclusions on the effect of the different TEs and their repetition on eating symptoms and their severity.


c-Myc and eIF4F are components of a feedforward loop that links transcription and translation.
The Myc/Max/Mad family of transcription factors and the eukaryotic initiation factor 4F (eIF4F) complex play fundamental roles in regulating cell growth, proliferation, differentiation, and oncogenic transformation. eIF4F is involved in the recruitment of ribosomes to mRNAs and is thought to generally be the rate-limiting phase of translation. Here, we show that c-Myc directly activates transcription of the three subunits of eIF4F (eIF4E, eIF4AI, and eIF4GI). These transcriptional effects are mediated through canonical E-boxes (5'CACGTG3') present in the promoters of these genes. In addition, the c-Myc antagonist Mad1 down-regulates the expression of eIF4F subunits. We also show that MycER activation stimulates protein synthesis at the level of translation initiation. Increased eIF4F levels result in stimulation of c-Myc mRNA translation specifically, as assessed by quantitative reverse transcription-PCR. We use a murine model of lymphomagenesis to show the expression of eIF4F subunits is also up-regulated by c-Myc in vivo. Our results suggest the presence of a feedforward loop involving c-Myc and eIF4F that serves to link transcription and translation and that could contribute to the effects of c-Myc on cell proliferation and neoplastic growth.


Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining.
The efficient repair of double-strand breaks (DSBs) in DNA is critical for the maintenance of genome stability. In mammalian cells, repair can occur by homologous recombination or by non-homologous end joining (NHEJ). DNA breaks caused by reactive oxygen or ionizing radiation often contain non- conventional end groups that must be processed to restore the ligatable 3'-OH and 5'-phosphate moieties which are necessary for efficient repair by NHEJ. Here, using cell-free extracts that efficiently catalyse NHEJ in vitro, we show that human polynucleotide kinase (PNK) promotes phosphate replacement at damaged termini, but only within the context of the NHEJ apparatus. Phosphorylation of terminal 5'-OH groups by PNK was blocked by depletion of the NHEJ factor XRCC4, or by an inactivating mutation in DNA-PK(cs), indicating that the DNA kinase activity in the extract is coupled with active NHEJ processes. Moreover, we find that end-joining activity can be restored to PNK-depleted extracts by addition of human PNK, but not bacteriophage T4 PNK. This work provides the first demonstration of a direct, specific role for human PNK in DSB repair.


Successful pregnancy after D-penicillamine therapy in a patient with Wilson's disease.
Infertility and amenorrhea are reported in most cases of Wilson's disease. In this report, we describe a case of Wilson's disease with pancytopenia and liver cirrhosis for over 4 years, without any specific treatment. After 2 years of D-penicillamine therapy, the patient became pregnant and delivered a liver mature female baby with a body weight of 2,800 g. Both before the pregnancy and after delivery, brainstem auditory evoked potential studies showed similar bilaterally abnormal prolongation in the III-V and I-V intervals. In visual evoked potentials, the P 100 latency was delayed bilaterally. Although serial evoked potential studies failed to show any improvement, a successful pregnancy was proven to be possible in a patient with Wilson's disease who had received regular D-penicillamine treatment.


Analysis of Nano-ZnO-Modified Asphalt Compatibility Based on Molecular Dynamics.
Nano-ZnO has a large specific surface area, small particle size, and strong polarity and can be used as an additive to modify the base asphalt. In this paper, the compatibility mechanism between nano-ZnO modifier and asphalt is analyzed. Solubility parameters, interaction energNano-ZnO and mean square displacement of nano-ZnO in matrix asphalt were calculated at different temperatures to study the compatibility of the nano-ZnO modifier and the matrix asphalt. The radial distribution functions and radii of gyration of the asphalt's four components under the action of the nano-ZnO additive were calculated to investigate the effect of nano-ZnO on the molecular structure of the asphalt. The results show that the best compatibility between nano-ZnO and matrix asphalt is observed at 150 °C, especially when the nano-ZnO particle size was 6 Å. The particle sizes of nano-ZnO have little effect on the temperature at which the nano-ZnO-modified asphalt achieved its highest structural stability. Around 150 °C, the nano-ZnO-modified asphalt system with different particle sizes exhibit the highest stability and best compatibility. The addition of nano-ZnO improves the compactness of the asphalt structure and makes the asphalt more stable.


[Clinical pathological characteristics of resectable papillary thyroid microcarcinoma].
Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm). Results: The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto's thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82). Conclusions: Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.


Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and possible mechanisms.
Some research has shown that androgen has a neuroprotection against hypoxia-ischemia brain damage (HIBD). However, the relevant mechanism has not been fully elucidated. This study aimed to explore the neuroprotection of androgen against HIBD in neonatal rats and the possible mechanism. Sixty-four seven-day-old Sprague-Dawley (SD) rats were randomly assigned into three groups: Sham-operation, HIBD and Androgen. The HIBD model was induced by ligation of the left carotid common artery along with hypoxia exposure in neonatal rats from the latter two groups. The Sham-operation group was not subjected to hypoxia-ischemia (HI). The Androgen intervention group received an injection of testosterone propionate (25 mg/kg) immediately after HIBD. Bcl-2 and Bax protein expressions in the cortex and hippocampal CA region were detected by immunohistochemical method at 6, 24 and 72 hrs and at 7 days after HI. The contents of SOD and MDA in the brain tissue homogenate were measured by the thiobarbituric acid (TBA) method and the xanthine oxidase luminescence method respectively at 6, 24 and 48 hrs after HI. There were few Bcl-2 and Bax immune positive cells in the cortex or hippocampus in the left hemisphere in the Sham-operation group at 6 hrs after operation. This was significantly different from the HIBD control and Androgen intervention groups (P < 0.01). The expression of Bcl-2 protein in the cortex and hippocampus of the Androgen intervention group was significantly higher than that of the HIBD control group at 6, 24 and 72 hrs after HI (P < 0.05 or 0.01). The expression of Bax protein in the cortex and hippocampus of the Androgen intervention group was significantly lower than that of the HIBD control group at 24 hrs after HI (P < 0.05). The SOD content in the brain tissue homogenate of the HIBD control group was significantly reduced, in contrast, the MDA content in the brain tissue homogenate of the HIBD control group increased significantly at 6 hrs after HI compared with the Sham-operation group (P < 0.05). The SOD content was reduced to a nadir and the MDA content increased to a peak at 24 hrs after HI in the HIBD control group. Androgen intervention increased significantly the SOD activity at 6,24 and 48 hrs after HI and decreased significantly the MDA content at 6 and 24 hrs after HI as compared with the HIBD control group (P < 0.05 or 0.01). The neuroprotection of androgen against neonatal HIBD is produced possibly through an increase of Bcl-2 protein expression and a reduction in Bax protein expression, thus decreasing neuronal apoptosis after HI. There may also be a reduction in the consumption of antioxidant and an inhibition of the formation of oxidant free radicals to alleviate neuronal damage following HI.


Prevalence of p53, bcl-2, and Ki-67 immunoreactivity and of apoptosis in normal oral epithelium and in premalignant and malignant lesions of the oral cavity.
Loss of normal p53 is correlated to the progression of several preneoplastic lesions to neoplasms, and overexpression of bcl-2 determines an alteration of programmed cell death. There is an increased awareness of the importance of apoptosis in cancerogenesis, and a strong correlation of Ki-67 with high tumor grade has been reported. The aim of our study was to investigate immunohistochemically the expression and relationship of p53, bcl-2, MIB-1, and the apoptotic index (AI) in normal oral epithelium, leukoplakia, dysplasia, and oral squamous cell carcinoma. A strong correlation was found between p53 overexpression and cell proliferation (MIB-1) and the AI. An inverse relationship was found between bcl-2 expression and MIB-1 and AI. A significant inverse relationship was found between p53 and bcl-2. A good positive correlation was present between AI and MIB-1 expression. Apoptosis could be important to help to understand oral carcinogenesis.


Obesity indices for prediction of chronic kidney disease: a cross-sectional study in 26 655 Chinese adults.
To investigate the associations between chronic kidney disease (CKD) and body mass index (BMI), waist circumference(WC), waist-to-height ratio (WheiR) in Chinese adults. A total of 26 655 participants, who voluntarily attended annual health examination at the Health Management Center in the Third Xiangya Hospital of Central South University from June 2013 to February 2014, were enrolled for this study. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed. The prevalence rate of CKD was 9.6% and 3.1% in male and female subjects, respectively. Multivariate logistic regression analysis showed that BMI, WC and WheiR were independent risk factors for CKD in diabetic male and hypertensive male subjects (P<0.01). However, no association between these obesity indices and CKD was found in women after multivariate adjustment. In diabetic male subjects, when BMI≥28.7 kg/m(2), WC=90.7 cm and WheiR=0.56, the sensitivity and specificity prediction for CKD was 24.8%, 58.5%, 45.5% and 83.3%, 54.4%, 69.6%, respectively. In hypertensive male subjects, when the optimum cut-off points for BMI, WC and WheiR were ≥ 27.0 kg/m(2), 91.2 cm and 0.54, the sensibility prediction for CKD were 41.0%, 47.0% and 50.1%, respectively, while the specificity prediction were 68.0%, 63.0% and 61.4%, respectively. The area under the ROC curve of BMI, WC, WheiR for CKD prediction were 0.56, 0.57, 0.59 in diabetic male subjects and 0.54, 0.56, 0.57 in hypertensive male subjects, respectively. BMI, WC and WheiR are associated with the increased risk for CKD in diabetic or hypertensive male subjects. However, the value for these obesity indices is limited in screening CKD.


Incidence of presumed steroid response in contralateral eye of patients who underwent glaucoma filtration surgery.
The aim of this study was to report the incidence of presumed steroid response in contralateral eye of patients who underwent glaucoma filtration surgery. We reviewed records of 298 glaucoma patients (147 PACG [primary angle-closure glaucoma], 129 POAG [primary open-angle glaucoma], and 22 JOAG [juvenile open-angle glaucoma]) who underwent either trabeculectomy alone or trabeculectomy with cataract extraction. All patients received prednisolone acetate 1% eye drop postoperatively in the operated eye for up to 6 to 8 weeks. The contralateral eye received the same antiglaucoma medications as before. Information collected included age, sex, number of antiglaucoma medications in the fellow eye preoperatively, and VFI (visual field index). The preoperative intraocular pressure (IOP) in the contralateral eye was taken as the baseline. The maximum IOP recorded postoperatively up to a follow-up period of 6 to 8 weeks was noted. A steroid response was defined as rise in the IOP by ≥6 mmHg. In this study, 298 eyes of 298 glaucoma patients were included. The mean age of patients was 60.1 ± 13.7 years. The mean number of antiglaucoma medications in the fellow eye pre-operatively was 2.4 ± 1.2. Mean preoperative and postoperative IOP in the fellow eye were 17.46 ± 7 and 19.37 ± 7.1 mmHg, respectively. Sixty-three eyes out of 298 eyes (21.14%) showed a rise in IOP by 6 mmHg. The maximum IOP difference noted was 15 mmHg. The average time interval to the defined steroid response was 16.13 days. The majority showed a steroid response within 19 days. Steroid response is a significant factor leading to elevated IOP postoperatively in the contralateral eye as well.


China's COVID-19 Control Strategy and Its Impact on the Global Pandemic.
Public health crises are challenging for governments and health systems, and coronavirus disease 2019 (COVID-19) has presented huge challenges to humans worldwide. In the context of COVID-19 in China, we explore China's control strategies and challenges. Our analysis examines seven strategies: digital technology pandemic prevention, zero-case policy, all-staff nucleic acid testing, all-staff vaccinations, the long-term quarantine system, and the official accountability system. Additionally, it considers three challenges: repeated pandemic waves, increased downward pressure on the economy and social exhaustion. We identify the causes of these challenges, including social and natural factors, and the controls put in place. We contend that China's control strategies slowed the spread of the global pandemic and that Chinese vaccines have promoted global vaccine equity.


Early neuronal alterations caused by experimental thinner inhalation in young rats.
Young rats were treated with thinner inhalations (50 and 100 p.p.m., v/v). The brains of treated and control animals were studied with standard techniques of light and electron microscopy and with ultrastructural cytochemical method for localization of RNA. No alterations were found in the group treated with a single session of inhalation, irrespective of the dose. Animals treated with 10 or 20 sessions showed altered neurons in cerebral cortex, caudate nucleus, hypothalamus and cerebellar cortex. More frequent alterations were: small nucleoli with loss of their reticular structure and a marked decrease of their normal granular component; diminution of perichromatin fibrils and of ribosomes. In the animals treated with high doses of thinner (20 sessions, 100 p.p.m.) a small number of neurons show an increased amount of lysosomes, autophagosomes and neurofibrillar hypertrophy. These results suggest that thinner inhalation causes an initial impairment of gene transcription and of RNA processing followed by neuronal degeneration.


Exploring the alternative virulence determinants PB2 S155N and PA S49Y/D347G that promote mammalian adaptation of the H9N2 avian influenza virus in mice.
The occurrence of human infections caused by avian H9N2 influenza viruses has raised concerns regarding the potential for human epidemics and pandemics. The molecular basis of viral adaptation to a new host needs to be further studied. Here, the bases of nucleotides 627 and 701 of PB2 were changed according to the uncoverable purine-to-pyrimidine transversion to block the development of PB2 627K and 701N mutations during serial passaging in mice. The purpose of this experiment was to identify key adaptive mutations in polymerase and NP genes that were obscured by the widely known host range determinants PB2 627K and 701N. Mouse-adapted H9N2 variants were obtained via twelve serial lung-to-lung passages. Sequence analysis showed that the mouse-adapted viruses acquired several mutations within the seven gene segments (PB2, PB1, PA, NP, HA, NA, and NS). One variant isolate with the highest polymerase activity possessed three substitutions, PB2 S155N, PA S49Y and D347G, which contributed to the highly virulent and mouse-adaptative phenotype. Further studies demonstrated that these three mutations resulted in increased polymerase activity, viral transcription and replication in mammalian cells, severe interstitial pneumonia, excessive inflammatory cellular infiltration and increased growth rates in mice. Our results suggest that the substitution of these three amino acid mutations may be an alternative strategy for H9N2 avian influenza viruses to adapt to mammalian hosts. The continued surveillance of zoonotic H9N2 influenza viruses should also include these mammalian adaptation markers as part of our pandemic preparedness efforts.


[Association of polymorphism of GSTT1 and GSTM1 genes with infertility in men].
To identify the association between homozygous deletion genotypes of glutathione transferase genes GSTT1 (glutathione transferase theta 1), GSTM1 (glutathione S-transferase mu1) and infertility in Russian men. The article presents a comparative analysis of the incidence of homozygous deletion genotypes of glutathione transferase genes GSTM1 and GSTT1 in Russian men with and without infertility. The study group comprised 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years.) The infertility diagnosis was verified according to the WHO guidelines. The control group comprised 104 healthy Russian volunteers (mean age 31.3+/-5.4 years.) Molecular genetic detection of GSTM1 and GSTT1 deletion polymorphisms was performed using PCR. The genomic DNA for the study was extracted from whole blood samples. The study and control group differed significantly in incidence of GSTM1 (p=0.043) and GSTT1 (p=0.008) deletion polymorphisms. The probability of detecting "zero" genotypes of the GSTT1 and GSTM1 genes in infertile men was 2.5 (p<0.05) and 1.7 times higher (p<0.05), respectively, than in fertile men. Therefore, the study findings allow us to conclude that the deletion genotypes of GSTM1 and GSTT1 are associated with infertility in Russian men. Molecular genetic analysis of deletion polymorphism of glutathione transferase genes can be recommended for a comprehensive examination of infertile men.


Exploring Well-being at Work-An Interview Study on How IT Professionals Perceive Their Workplace.
The workplace is particularly important for promoting well-being at work and general life satisfaction, as performing a professional activity can be perceived as satisfying and motivating. In addition, employment opens up opportunities for individual development that employees may be perceived as fulfilling. By conducting an interview study with IT professionals of a German medium-sized company, we investigate which factors of the individual work environment are perceived as conducive to the performance of everyday job duties and thus increase well-being at work. Furthermore, we analyze the extent to which participants are satisfied with the implementation of the factors that are important to them, whether socio-demographic differences are relevant, and whether the perception of the work environment has an effect on employees' commitment. Results show that interpersonal factors in particular are considered to be important in everyday working life. About individual factors, a mixed picture emerged, whereby sociodemographic differences play only a minor role. Furthermore, there are indications of a positive relationship between the perception of the work environment and the IT professionals' commitment. In-depth analysis of the employee statements helps to determine which aspects of the work environment should be implemented, developed, or promoted. In the long term, this can support individual learning and development paths and generates a work environment that sustainably promotes employees' well-being at work and fosters long-term employment relationships.


The effect of a comprehensive handwashing program on absenteeism in elementary schools.
Handwashing is one of the most important factors in controlling the spread of micro-organisms and in preventing the development of infections. The objective of this study was to determine the effectiveness of a comprehensive handwashing program on absenteeism in elementary grades. Two hundred ninety students from 5 independent schools were enrolled in the study. Each test classroom had a control classroom, and only the test classroom received the intervention (education program and hand sanitizer). Absenteeism data were collected for 3 months. The number of absences was 50.6% lower in the test group (P <.001). The data strongly suggest that a hand hygiene program that combines education and use of a hand sanitizer in the classroom can lower absenteeism and be cost-effective.


Kommerell Diverticulum Should Be Removed in Children With Vascular Ring and Aberrant Left Subclavian Artery.
Right aortic arch with aberrant left subclavian artery is the most frequent cause of vascular ring. Ligamentum arteriosus division opens the ring but leaves the Kommerell diverticulum in place, with a risk of residual compression, aneurysmal dilation, dissection, or even rupture. A procedure consisting of translocation of the aberrant left subclavian artery to the left carotid artery with removal of the Kommerell diverticulum and division of the ligamentum is currently advocated. Between September /2009 and August 2011, 12 consecutive patients underwent the foregoing procedure. Clinical findings, surgical procedure, complications, histopathologic findings, and follow-up data were retrospectively analyzed. Mean age at the time of operation was 7.7 years (median, 4.3 years, range, 0.9 to 18.9 years), and mean weight was 26 kg (median, 18 kg; range, 8.4 to 59 kg). All patients had symptoms. Computed tomography scan or magnetic resonance imaging, or both, had confirmed the diagnosis in all patients. Postoperative events, all transient, included chylothorax (1 patient), phrenic palsy (1 patient), pneumonia (1 patient), and the need for prolonged chest drainage (3 patients). Mean follow-up reached 19 months (median, 13 months; range, 12 to 41 months). Mild residual respiratory symptoms were noted in 3 patients. Echo-Doppler analysis showed a patent left subclavian-to-carotid artery anastomosis. Histopathologic analysis of the resected diverticulum (n = 6) showed cystic medial necrosis in four diverticula (focal in one). Translocation of the aberrant left subclavian artery with diverticulum resection and ligamentum division is an efficient procedure for symptom relief. Profound wall abnormalities such as medial necrosis in at least 50% of the analyzed diverticula encourage us to maintain this strategy, to reduce the risk of aneurysm formation and dissection.


Accommodating negative intracluster correlation with a mixed effects logistic model for bivariate binary data.
We extend the random intercept logistic model to accommodate negative intracluster correlations for bivariate binary response data. This approach assumes a single random effect per cluster, but entails separate affine transformations of this random effect for the two responses of the pair. We show this approach works for two data sets and a simulation, whereas other mixed effects approaches fail. The two data sets are from a crossover trial and a developmental toxicity study of the effects of chemical exposure on malformation risk among rat pups. Comparisons are made with the conditional likelihood approach and with generalized estimating equations estimation of the population-averaged logit model. Simulations show the conditional likelihood approach does not perform well for moderate to strong negative correlations, as a positive intracluster correlation is assumed. The proposed mixed effects approach appears to be slightly more conservative than the population-averaged approach with respect to coverage of confidence intervals. Nonetheless, the statistical literature suggests that mixed effects models provide information in addition to that provided by population-averaged models under scientific contexts such as crossover trials. Extensions to trivariate and higher-dimensional responses also are addressed. However, such extensions require certain constraints on the correlation structure.


Host involvement in vaccinia virus replication.
Nutrient-depleted conditions, which induced an inhibited state in uninfected cell monolayers, rendered the cells nonpermissive for vaccinia virus, while not affecting their ability to support propagation of an unrelated mengovirus. When the inhibited state was reversed, the ability to propagate vaccinia virus was restored. The inhibited cells retained the ability to support some early-induced events (thymidine kinase synthesis and its arrest, which are DNA synthesis-independent functions in a mouse cell host), but lost the ability to support some others (sensitization of input viral DNA to DNase, induction of DNA polymerase synthesis, and virus-induced CPE). The data are consistent with involvement of a host factor(s) in induction of early vaccinia virus-induced events in infected cells.


mRNA expression and RNA editing (2451 C-to-U) of IL-12 receptor beta2 in adult atopic patients.
Interleukin (IL)-12 activates T helper (Th) 1 cells to produce interferon (IFN)-gamma which inhibits atopic inflammation. IL-12 acts through interaction with its receptor, especially beta(2) subunit. In several studies, the low production of IFN-gamma in peripheral mononuclear cells of atopic patients on response to IL-12 stimulation has been reported. Therefore we investigated the IL-12 receptor beta(2) (IL-12R beta(2)) mRNA expression and RNA editing, nucleotide 2451 C-to-U conversion, to find the cause of low responsiveness to IL-12 in atopy. Quantitative real time PCR for mRNA expression and sequence analysis for RNA editing were performed in 80 atopic patients and 54 healthy controls. The expression of IL-12R beta(2) mRNA was significantly lower in atopic patients than healthy controls (p<0.05). In sequence analysis, RNA editing on nucleotide 2451 was not found from either atopic patients or healthy controls. In additional evaluation, there was no relationship between expression of IL-12R beta(2) mRNA and serum total IgE or blood eosinophil count. Reduced IL-12R beta(2) mRNA expression in atopic patients indicate the reduced capacity to respond to IL-12 which induce IFN-gamma production and this may contribute to Th2-skewed immune response in atopy.


Engineering skeletal muscle tissue in bioreactor systems.
To give a concise review of the current state of the art in tissue engineering (TE) related to skeletal muscle and kinds of bioreactor environment. The review was based on data obtained from the published articles and guidelines. A total of 106 articles were selected from several hundred original articles or reviews. The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of engineered muscle tissue in bioreactor. Skeletal muscle TE is a promising interdisciplinary field which aims at the reconstruction of skeletal muscle loss. Although numerous studies have indicated that engineering skeletal muscle tissue may be of great importance in medicine in the near future, this technique still represents a limited degree of success. Since tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen, carbon dioxide, nutrients and waste products. Moreover, functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural cells. Third, in order to engineer muscle tissue successfully, it may be beneficial to mimic the in vivo environment of muscle through association with adequate stimuli from bioreactors. Vascular system and bioreactors are necessary for development and maintenance of engineered muscle in order to provide circulation within the construct.


Inactivation of Heat Adapted and Chlorine Adapted Listeria Monocytogenes ATCC 7644 on Tomatoes Using Sodium Dodecyl Sulphate, Levulinic Acid and Sodium Hypochlorite Solution.
The effectiveness of sodium dodecyl sulphate (SDS), sodium hypochlorite solution and levulinic acid in reducing the survival of heat adapted and chlorine adapted Listeria monocytogenes ATCC 7644 was evaluated. The results against heat adapted L. monocytognes revealed that sodium hypochlorite solution was the least effective, achieving log reduction of 2.75, 2.94 and 3.97 log colony forming unit (CFU)/mL for 1, 3 and 5 minutes, respectively. SDS was able to achieve 8 log reduction for both heat adapted and chlorine adapted bacteria. When used against chlorine adapted L. monocytogenes sodium hypochlorite solution achieved log reduction of 2.76, 2.93 and 3.65 log CFU/mL for 1, 3 and 5 minutes, respectively. Using levulinic acid on heat adapted bacteria achieved log reduction of 3.07, 2.78 and 4.97 log CFU/mL for 1, 3, 5 minutes, respectively. On chlorine adapted bacteria levulinic acid achieved log reduction of 2.77, 3.07 and 5.21 log CFU/mL for 1, 3 and 5 minutes, respectively. Using a mixture of 0.05% SDS and 0.5% levulinic acid on heat adapted bacteria achieved log reduction of 3.13, 3.32 and 4.79 log CFU/mL for 1, 3 and 5 minutes while on chlorine adapted bacteria it achieved 3.20, 3.33 and 5.66 log CFU/mL, respectively. Increasing contact time also increased log reduction for both test pathogens. A storage period of up to 72 hours resulted in progressive log reduction for both test pathogens. Results also revealed that there was a significant difference (P≤0.05) among contact times, storage times and sanitizers. Findings from this study can be used to select suitable sanitizers and contact times for heat and chlorine adapted L. monocytogenes in the fresh produce industry.


Determination of ochratoxin A by monoclonal antibody-based enzyme immunoassay.
A simple and rapid indirect enzyme-linked immunosorbent assay was developed for the quantitative determination of ochratoxin A in barley after the successful production of a high affinity, specific monoclonal antibody. A rapid sample cleanup was achieved by extracting ochratoxin A from barley with chloroform and partitioning the toxin into bicarbonate buffer; the buffer solution was then added directly to the assay plate and ochratoxin A content was assessed. Recoveries were greater than 85% and detection limits were 5 micrograms ochratoxin A/kg barley.


Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase.
Imatinib is a tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). BCR-ABL mutations are associated with failure of imatinib treatment in many CML patients. LYN kinase regulates survival and responsiveness of CML cells to inhibition of BCR-ABL kinase, and differences in LYN regulation have been found between imatinib-sensitive and -resistant CML cell lines. We evaluated cells from 12 imatinib-resistant CML patients with mutation-negative BCR-ABL and from six imatinib-sensitive patients who discontinued therapy because of imatinib intolerance. Phosphorylation of BCR-ABL and LYN was assessed in patient cells and cell lines by immunoblotting with activation state-specific antibodies, co-immunoprecipitation studies, and mass spectroscopy analysis of phosphopeptides. Cell viability, caspase activation, and apoptosis were also measured. Mutations were analyzed by sequencing. The effect of silencing LYN with short interfering RNAs (siRNAs) or reducing activation by treatment with tyrosine kinase inhibitors was evaluated in cell lines and patient cells. Imatinib treatment suppressed LYN phosphorylation in cells from imatinib-sensitive CML patients and imatinib-sensitive cell lines. Imatinib treatment blocked BCR-ABL signaling but did not suppress LYN phosphorylation in cells from imatinib-resistant patients, and persistent activation of LYN kinase was not associated with mutations in LYN kinase or its carboxyl-terminal regulatory domains. Unique LYN phosphorylation sites (tyrosine-193 and tyrosine-459) and associated proteins (c-Cbl and p80) were identified in cells from imatinib-resistant patients. Reducing LYN expression (siRNA) or activation (dasatinib) was associated with loss of cell survival and cytogenetic or complete hematologic responses in imatinib-resistant disease. LYN activation was independent of BCR-ABL in cells from imatinib-resistant patients. Thus, LYN kinase may be involved in imatinib resistance in CML patients with mutation-negative BCR-ABL and its direct inhibition is consistent with clinical responses in these patients.


Involvement of oxo-bridged binuclear iron centers in oxygen transport, oxygen reduction, and oxygenation.
The occurrence of an oxo-bridged binuclear iron site is well-established for the oxygen transport protein, hemerythrin, and strongly implicated in ribonucleotide reductase, purple acid phosphatase, ferritin, and methane monooxygenase. Key identifying characteristics are an antiferromagnetic interaction between the two iron atoms, an Fe-O-Fe vibrational mode in the resonance Raman spectrum, and an S = 1/2 EPR signal upon one-electron reduction. In hemerythrin the oxo bridge serves as a hydrogen bond acceptor which stabilizes the bound hydroperoxide. In ribonucleotide reductase both the binuclear iron center and a protein tyrosine undergo oxidation in the presence of molecular oxygen, whereas in methane monooxygenase a binuclear iron moiety may activate O2 for substrate oxygenation.


An evaluation of routine antenatal depression screening and psychosocial assessment in a regional private maternity setting in Australia.
There is limited information relating to routine depression screening and psychosocial assessment programs in private maternity settings in Australia. To describe the psychosocial profile of a sample of private maternity patients who participated in a depression screening and psychosocial risk assessment program as part of routine antenatal care, and to explore women's experience of receiving this component of pregnancy care. We conducted a retrospective medical records audit of 455 consecutive women having a routine psychosocial assessment and referral. Assessment was undertaken using the Edinburgh Postnatal Depression Scale (EPDS) and the Antenatal Risk Questionnaire (ANRQ) for psychosocial risk; 101 women completed a feedback survey about their experience of receiving routine psychosocial care. Of the 87.7% of women who completed both EPDS and ANRQ, 4.3% scored 13 or more on the EPDS. On the ANRQ, 25.3% of women endorsed one risk factor, 11.6% two risk factors and 10.5% three or more risk factors. Elevated EPDS scores were associated with major stresses in the last 12 months, high trait anxiety and significant past mental health issue/s. Acceptability of depression screening and psychosocial risk assessment was high. This study highlights the need for, and acceptability of, depression and psychosocial assessment in the private maternity sector. These findings are particularly timely given the provision of new Medicare Benefits Scheme items for obstetricians to undertake psychosocial assessment (both antenatally and postnally) in line with recommended clinical best practice.