Acquired resistance to miriplatin in rat hepatoma AH109A/MP10 is associated with increased Bcl-2 expression, leading to defects in inducing apoptosis.
Miriplatin, a novel lipophilic platinum complex approved to treat hepatocellular carcinoma, is administered into the hepatic artery after suspension in an oily contrast medium. Little is known concerning the mechanism of acquired resistance to miriplatin. In this study, we established and characterized a rat hepatoma cell subline, AH109A/MP10, which was about 10-fold more resistant to miriplatin than the parental cell line, AH109A. The established miriplatin-resistant cells showed clear cross-resistance to platinum complexes containing diaminocyclohexane as a carrier ligand, such as oxaliplatin and dichloro[(1R,2R)-1,2-cyclohexanediamine-N,N']platinum (DPC), while three human cancer cell lines selected for resistance to cisplatin (A2780cis, NCI-H69/CPR, MOR/CPR) did not show cross-resistance to miriplatin. There was no apparent difference in either intracellular platinum accumulation or platinum-DNA adducts in formation between resistant and parental cells after treatment with miriplatin or cisplatin, consisted with the unchanged expression of proteins involved in DNA repair, such as excision repair cross-complementing 1 (ERCC1) and mutL homolog 1 (MLH1). The increased expression of Bcl-2 was observed in AH109A/MP10 cells, in which apoptosis induced by miriplatin, but not cisplatin, was reduced. In addition, Bcl-2 inhibitor YC137 partially reversed the resistance of AH109A/MP10 cells to miriplatin. These findings suggested that the acquired resistance to miriplatin in AH109A/MP10 cells was associated in part with increased Bcl-2 expression, leading to defects in inducing apoptosis.


The present state and future prospects of occupational health in Bangladesh.
Bangladesh is a relatively young and developing country. At the present time, like in most developing countries, a clear demarcation between occupational health care and general medical care is difficult to be recognized in Bangladesh. Occupational health is a fairly new field, as the country is undergoing industrialization and occupational health activities are operated by several ministries, such as Labour, Health, Industry and Transport. Legal foundations of the occupational health-care system based on British India and Pakistani era, were adopted and amended by the Government of Bangladesh after the liberation of the country in 1971. Most of the Labour laws have been rectified by the Government of Bangladesh according to the ILO Conventions. Reconsideration of the occupational health service system avoiding duplication for the 'occupational health' component in several ministries might be helpful to achieve the successful provision of an occupational health service in the developing Bangladesh.


[Hepatoid adenocarcinoma of the stomach. Case report and review of the literature].
Hepatoid adenocarcinoma of the stomach is an uncommon gastric tumor. A throughout search of the literature revealed only 86 cases: the first case was reported by Bourreille et al in 1970. We describe a patient with primary gastric adenocarcinoma with high serum alpha-fetoprotein (AFP) levels (7000 ng/ml). Histologically foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Immunoreactivity for alpha-fetoprotein (AFP), a1 antitrypsin and CEA also indicate hepatocellular differentiation. This case provides informations on the DNA content and Ki67 expression of this unusual and aggressive variant of gastric adenocarcinoma.


Genetic similarity among Cercospora apii-group species and their detection in host plant tissue by PCR/RFLP analyses of the rDNA internal transcribed spacer (ITS).
The objective of this study was to determine the genetic relatedness among the Cercospora and Pseudocercospora species closely related to Cercospora apii by using a polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of the internal transcribed spacer (ITS) region. A single PCR fragment (about 550 bp) was obtained from all Cercospora species categorized as the C. apii-group, Pseudocercospora purpurea, Pseudocercospora conyzae, and Pseudocercospora cavarae. Cercospora caricis yielded a 680 bp PCR fragment. The similarity in the PCR fragment size and RFLP profiles among the C. apii-group isolates, including Pseudocercospora purpurea, and Pseudocercospora conyzae strongly suggests that these species are conspecific. Synonymy with C. apii (lectotype) at a subspecific rank has been proposed. Amplified ITS regions of genomic DNA extracted from spinach leaves showing 12 and 233% leaf spot disease symptoms caused by Cercospora beticola yielded two PCR fragments (i.e., one from the fungus and one from the host plant) and were resolved by electrophoresis of the PCR product in 3% LMP agarose. Digestion of the total PCR product with HinfI restriction enzyme yielded RFLP profiles similar to those obtained from amplified DNA from the causative agent, C. beticola. The method described in this preliminary study offers rapid detection and diagnosis of fungal infections in plants for disease prediction and management and screening of plant materials for quarantine purposes.


Overexpression of Lysine-Specific Demethylase 1 Is Associated With Tumor Progression and Unfavorable Prognosis in Chinese Patients With Endometrioid Endometrial Adenocarcinoma.
Lysine-specific demethylase 1 (LSD1) is a kind of flavin adenine dinucleotide-dependent amine oxidase that regulates normal cellular differentiation, gene activation, tumorigenesis, and progression. This study aims to detect the expression level of LSD1 in endometrial cancer and to explore its role in the progression and prognosis of endometrioid endometrial adenocarcinoma (EEA). Immunohistochemistry was used to examine the expression of LSD1 in 206 EEA specimens, 50 benign endometrial lesion specimens, and 45 normal endometrium specimens. χ Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were applied for the statistical analysis. Compared with normal endometrium and benign endometrial lesion (both P < 0.001), LSD1 was overexpressed in EEA. LSD1 expression was correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, vascular/lymphatic invasion, depth of myometrial invasion, and lymph node metastasis. Results of the Kaplan-Meier analysis indicated that LSD1 expression was associated with overall survival (OS) and disease-free survival (DFS) of EEA. The negative expression LSD1 group had longer OS and DFS than did the positive expression group. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that the LSD1 expression status was an independent prognostic factor for both OS (P = 0.027) and DFS (P = 0.016) of patients with EEA. Overexpression of LSD1 may contribute to the progression of EEA and may thus serve as a new biomarker to predict the prognosis of EEA.


[Synergistic drug combination prediction in multi-input neural network].
Synergistic effects of drug combinations are very important in improving drug efficacy or reducing drug toxicity. However, due to the complex mechanism of action between drugs, it is expensive to screen new drug combinations through trials. It is well known that virtual screening of computational models can effectively reduce the test cost. Recently, foreign scholars successfully predicted the synergistic value of new drug combinations on cancer cell lines by using deep learning model DeepSynergy. However, DeepSynergy is a two-stage method and uses only one kind of feature as input. In this study, we proposed a new end-to-end deep learning model, MulinputSynergy which predicted the synergistic value of drug combinations by integrating gene expression, gene mutation, gene copy number characteristics of cancer cells and anticancer drug chemistry characteristics. In order to solve the problem of high dimension of features, we used convolutional neural network to reduce the dimension of gene features. Experimental results showed that the proposed model was superior to DeepSynergy deep learning model, with the mean square error decreasing from 197 to 176, the mean absolute error decreasing from 9.48 to 8.77, and the decision coefficient increasing from 0.53 to 0.58. This model could learn the potential relationship between anticancer drugs and cell lines from a variety of characteristics and locate the effective drug combinations quickly and accurately.


Linking practices with community programs to improve immunization rates.
Pediatricians should be knowledgeable about programs available in their community and support efforts to collaborate with other providers, public health departments and immunization coalitions in their community. Through immunization coalitions and widespread use of an immunization registry, together with participating private providers, case management and home visitation programs can improve immunization rates among the highest risk children.


Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.
Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor adherence. There was, however, no significant association with viral suppression. Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. April 28th 2014; NCT02126696 .


Responses of Atriplex spongiosa and Suaeda monoica to Salinity.
The growth and tissue water, K(+), Na(+), Cl(-), proline and glycinebetaine contents of the shoots and roots of two Chenopodiaceae, Atriplex spongiosa and Suaeda monoica have been measured over a range of external NaCl salinities. Both species showed some fresh weight response to low salinity mainly due to increased succulence. S. monoica showed both a greater increase in succulence (at low salinities) and tolerance of high salinities than A. spongiosa. Both species had high affinities for Na(+) and maintained constant but low shoot K(+) contents with increasing salinity. These trends were more marked with S. monoica in which Na(+) stimulated the accumulation of K(+) in roots. An association between high leaf Na(+) accumulation, high osmotic pressure, succulence, and a positive growth response at low salinities was noted. Proline accumulation was observed in shoot tissues with suboptimal water contents. High glycinebetaine contents were found in the shoots of both species. These correlated closely with the sap osmotic pressure and it is suggested that glycinebetaine is the major cytoplasmic osmoticum (with K(+) salts) in these species at high salinities. Na(+) salts may be preferentially utilized as vacuolar osmotica.


Sustainability Index (S-Index): A tool for use in the evaluation and planning of institutional animal collections.
Maintaining sustainable living collections is at the core of every zoo's and aquarium's mission. In spite of increasing awareness of sustainability challenges, few practical applications to support collection sustainability have been developed. In addition, much of the onus to address issues regarding collection sustainability has fallen to regional zoo associations, rather than on individual collection managers, creating a "tragedy of the commons." Responsibility for sustainability, however, ultimately defaults to each individual institution; as active participants in an association and the population management system, other institutions are the most reliable source of animals. Each collection manager must ensure that their collection contributes to association-wide sustainability. With this in mind, a sustainability index tool, S-Index, has been developed using basic demographic concepts and novel metrics for institutional collection evaluation. Furthermore, combining S-Index data across facilities allows the evaluation of the sustainability of individual taxa or taxonomic groups within the Association. An S-Index analysis of 27 Association of Zoos and Aquariums member avian collections over ten years demonstrates the use of this analytical tool.


Impact of yellow fever outbreaks on two howler monkey species (Alouatta guariba clamitans and A. caraya) in Misiones, Argentina.
Two yellow fever outbreaks (YFOs) occurred in northeastern Argentina between November 2007 and October 2008, seriously affecting populations of two howler monkey species: the brown howler Alouatta guariba clamitans and the black howler Alouatta caraya. Both howlers live syntopically in El Piñalito Provincial Park, Misiones, where four groups (36 individuals) were studied since January 2005. The first dead howlers were found on January 20, 2008, in El Piñalito. Systematic searches found 14 dead howlers within the area (12 from the study groups and two from neighboring groups), with only two young seen on January 25, 2008, and none found since up to December 2008. In October 2008, another YFO hit howler monkey populations from El Soberbio, Misiones. Overall, 59 howlers were found dead in Misiones from November 2007 to December 2008. Thanks to the alert of the howler's death in El Piñalito, a prompt human vaccination campaign started in the area. Wild howler monkey populations from both species are in a delicate situation in Misiones, especially the brown howler, an already endangered species in Argentina and endemic to the Atlantic Forest. If we add the recurrence of YFOs to the reduction of suitable habitat to small fragments, it could be only a matter of time until howler populations disappear from the Upper Paraná Atlantic Forest in Misiones.


Do doctors understand alcohol units?
A survey of 445 doctors in Yorkshire was conducted to ascertain their knowledge and awareness of alcohol units. Only 58% had some knowledge, and general practitioners scored better (69%) than hospital doctors (45%). However, 14% of doctors had no knowledge at all about alcohol units. Those who did not drink alcohol knew less than those who did and trainee doctors had significantly less knowledge than more senior physicians. Junior doctors who often deal with alcohol-related problems in their day-to-day hospital work had a poor knowledge. There needs to be a greater emphasis on alcohol and alcohol-related problems (including how to calculate alcohol units) in undergraduate and postgraduate curricula to improve doctors' knowledge and awareness of this important subject.


5-Oxoprolinase (l-Pyroglutamate Hydrolase) in Higher Plants: Partial Purification and Characterization of the Wheat Germ Enzyme.
5-Oxoprolinase has been found to be widely distributed in higher plants. This enzyme catalyzes the ATP-dependent hydrolysis of 5-oxo-l-proline (l-pyrollidone carboxylate, l-pyroglutamate) to glutamate. The enzyme has been purified almost 60 fold from wheat germ (Triticum aestivum L). This enzyme requires a divalent cation, either Mn(2+) or Mg(2+), and a combination of both appears to be the most effective. There is also an absolute requirement for a monovalent cation best fulfilled by either NH(4) (+) or K(+). The K(m) for ATP is 0.4 mm and for 5-oxo-l-proline is 14 mum. A small amount of activity is observed when other purine nucleotides such as ITP and GTP replace ATP. The substitution of the pyrimidine nucleotides CTP and UTP for ATP yield almost completely inactive preparations. The enzyme appears to have an active sulfhydryl group since there is an increase in activity in the presence of dithioerythritol. Preincubation with reagents such as N-ethylmaleimide or iodoacetamide lead to complete inactivation. The presence of this enzyme leads to the speculation of the possible presence of a gamma-glutamyl cycle in higher plants.


Identification of a high-affinity peripheral-type benzodiazepine binding site in rat aortic smooth muscle membranes.
The existence of a benzodiazepine binding site in rat aortic smooth muscle membranes was explored employing [3H]Ro5-4864 as radioligand. The binding site was concentrated in the mitochondrial fraction enriched with cytochrome c oxidase and semicarbazide-insensitive monoamine oxidase. [3H]Ro5-4864 binds to the membranes in the mitochondrial fraction with high affinity. The dissociation constant (KD) determined by saturation binding was 2.8 +/- 0.7 nM (n = 5). The association rate constant (k1) was 4.7 +/- 0.8 x 10(6) M1 min-1, and the dissociation rate constant (k-1) was 0.028 +/- 0.005 min-1 (n = 3). The kinetically determined KD was 6.0 +/- 0.8 nM (n = 3) at 0.5 nM [3H]Ro5-4864. The density of binding determined from saturation binding experiments was 14.0 +/- 1.2 pmol/mg protein (n = 5). The Hill coefficient of binding was 0.94 +/- 0.02 (n = 5) indicating that [3H] Ro5-4864 binds to a single site. The [3H]Ro5-4864 binding was inhibited by Ro5-4864 (Ki = 6.1 +/- 1.9 nM), PK 11195 (Ki = 8.9 +/- 1.8 nM), diazepam (Ki = 87.3 +/- 3.4 nM), flunitrazepam (Ki = 94.6 +/- 1.8 nM), clonazepam (Ki = 6.3 +/- 1.3 microM) and Ro15-1788 (Ki = 16.8 +/- 1.5 microM). The rank order of potency of the competitive inhibition of [3H]Ro5-4864 binding (Ro5-4864 = PK 11195 greater than diazepam = flunitrazepam much greater than clonazepam greater than Ro15-1788) is characteristic of the peripheral-type benzodiazepine binding site. The data indicate an abundant high affinity peripheral-type benzodiazepine binding site of unknown function in rat aortic smooth muscle cells.


What is Pain-Related Suffering? Conceptual Critiques, Key Attributes, and Outstanding Questions.
Suffering holds a central place within pain research, theory, and practice. However, the construct of pain-related suffering has yet to be operationalized by the International Association for the Study of Pain and is largely underdeveloped. Eric Cassell's seminal work on suffering serves as a conceptual anchor for the limited pain research that specifically addresses this construct. Yet, important critiques of Cassell's work have not been integrated within the pain literature. This Focus Article aims to take a preliminary step towards an updated operationalization of pain-related suffering by 1) presenting key attributes of pain-related suffering derived from a synthesis of the literature and 2) highlighting key challenges associated with Cassell's conceptualization of suffering. We present 4 key attributes: 1) pain and suffering are inter-related, but distinct experiences, 2) suffering is a subjective experience, 3) the experience of suffering is characterized by a negative affective valence, and 4) disruption to one's sense of self is an integral part of suffering. A key outstanding challenge is that suffering is commonly viewed as a self-reflective and future-oriented process, which fails to validate many forms of suffering and marginalizes certain populations. Future research addressing different modes of suffering - with and without self-reflection - are discussed. PERSPECTIVE: This article offers a preliminary step toward operationalizing the construct of pain-related suffering and proposes priorities for future research. A robust operationalization of this construct is essential to developing clinical strategies that aim to better recognize and alleviate suffering among people living with pain.


Temporomandibular joint condyle changes after surgically induced non-reducing disk displacement in rabbits: a macroscopic and microscopic study.
Experimentally induced displacement of the temporomandibular joint (TMJ) disk has previously been shown to induce shortening of the mandibular ramus on the ipsilateral side. The aim of this investigation was to reveal whether this shortening develops due to primary influence on condyle growth or by secondary loss of condyle mass due to degenerative tissue breakdown. Disk displacement was created in the right TMJ in seven 3-month-old rabbits, the posterior disk attachment kept intact. Seven rabbits underwent surgical opening of the TMJ without disk intervention. Seven additional animals served as references. After a 3-month experimental period, the animals were sacrificed. Previous analysis revealed shortening of mandibular height and length caused by ipsilateral TMJ disk displacement. The condyles were examined macroscopically and by histologic sectioning or scanning electron microscopy. All condyles were covered with smooth articulating soft tissue and without visible signs of degenerative changes. Four condyles from joints with disk displacement demonstrated substantial regressive remodeling resulting in a change of condyle shape with forward/downward rotation of an enlarged articulating surface. It was concluded that TMJ disk displacement in a growing individual can induce reduction of mandibular height and length before a stage where visible osteoarthrotic changes develop. It implies a primary adverse effect on condyle growth.


Two cases of placental sulphatase deficiency with unusual endocrine features.
Two cases of placental sulphatase deficiency are described both of which showed typical clinical features, associated with very low urinary and serum oestrogens. In the one case that reached term there was a spontaneous rise in serum oestradiol levels (from 16 to 44 nmol/l) after 38 weeks, although no oestradiol rise occurred after DHEAS loading. She later achieved a vaginal delivery. Although no steroid sulphatase activity could be detected in the placenta of case 2, there was a small transient rise in serum oestradiol (from 15.4 to 32.7 nmol/l) after maternal DHEAS loading. However, the absolute levels reached were very low compared to the response seen in normal pregnancies. The spontaneous rise in basal oestradiol levels between 38 and 41 weeks and the transient rise following DHEAS loading have not been previously reported for patients with placental sulphatase deficiency. Umbilical cord blood levels of several steroids in case 2 showed some similarities to previous case reports. Levels of DHEA, 16 alpha OH DHEA, 17OH pregnenolone and cortisol were significantly lower than control values. DHEAS, 16 alpha OH DHEAS, 17OH progesterone and androstenedione were within the normal range.


Black phosphorus nanoparticles for dual therapy of non-small cell lung cancer.
Lung cancer remains one of the leading causes of death in humans. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) commonly used to suppress tumour growth. However, constantly use of gefitinib results in drug-resistance, reduced efficacy and undesired side effects. To circumvent these drawbacks, targeted and photothermal therapies have emerged as effective strategies. Herein, we are first to adopt a black phosphorus (BP) nanoparticle-based novel delivering strategy by combining gefitinib and cancer cytomembrane to treat non-small cell lung cancer (NSCLC). In these gefitinib-containing nano-carriers, cyanine 5 (Cy5) biotin-labelled BP was incorporated with cancer membrane and then consists of a nanomaterial (BPGM), which enabled to deliver gefitinib to the tumours effectively. The combination of BPGM showed reinforcing effects to suppress NSCLC cells and xenograft tumours without apparent adverse effects both in vitro and in vivo. BPGM facilitated the delivery of gefitinib to tumour tissue and extended its retention time within tumours. These studies thus suggest that BP may serve as novel delivery strategy for lung cancer.


Targeting protein-protein interactions: a promising avenue of anti-HIV drug discovery.
In recent years, the number of useful chemical biology information of protein-protein interactions in the HIV life cycle and related inhibitors, is growing rapidly, which makes protein-protein interactions a new investigative area for antiviral drug intervention. This review will summarize recent work in this field, mainly focusing on the utilization of small molecules targeted against a variety of protein-protein interactions that have great therapeutic feasibility for HIV infection, and lastly outline some other important protein-protein interactions with a potential to advance into novel anti-HIV drug targets in future.


Concentrations of per- and polyfluoroalkyl substances (PFAS) in human placental tissues and associations with birth outcomes.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants commonly detected in human serum. Previous studies have observed associations between maternal serum PFAS and adverse pregnancy and birth outcomes such as lower birth weight or pre-eclampsia; however, few studies have explored these associations with birth outcomes and placental tissue PFAS concentration. The placenta is a vital contributor to a healthy pregnancy and may be involved in the mechanism of PFAS reproductive toxicity. Our goal was to measure placental PFAS concentrations and examine associations with birth outcomes (e.g., birth weight, gestational duration). Placenta samples (n = 120) were collected during delivery from women enrolled in the Healthy Pregnancy, Healthy Baby cohort (HPHB) in Durham, North Carolina. All placenta samples contained detectable PFAS, with perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) being the most abundant and most frequently detected (all >96% detection frequency). While placental PFAS concentrations did not differ by infant sex, higher PFAS levels were observed in placenta from nulliparous women, suggesting that parity influences the accumulation of PFAS in the placenta. We used linear regression models to examine associations between placental PFAS and birth outcomes. After adjustment for parity, tobacco use, maternal age, and maternal race, we found that placental PFOS was associated with lower birth weight for gestational age in male infants and higher birth weight for gestational age in female infants. Similar findings were seen for PFNA for birth weight for gestational age. These differences in birth outcomes based on infant sex highlight a need to explore mechanistic differences in PFAS toxicity during gestation for male and female infants.


The evolution of reciprocity: social types or social incentives?
The vast majority of human beings regularly engage in reciprocal cooperation with nonrelated conspecifics, and yet the current evolutionary understanding of these behaviors is insufficient. Intuitively, reciprocity should evolve if past behavior conveys information about future behavior. But it is not straightforward to understand why this should be an outcome of evolution. Most evolutionary models assume that individuals' past behavior informs others about their stable social type (defector, cooperator, reciprocator, etc.), which makes it sensible to reciprocate. In this article, after describing the central source of difficulty in the evolutionary understanding of reciprocity, I put forward an alternative explanation based on a work by O. Leimar. It consists of taking into account the fact that the payoffs to individuals in social interactions can change through time. This offers a solution because individuals' past behavior then signals their payoffs, which also makes it sensible to reciprocate. Even though the overwhelming majority of evolutionary models implicitly endorse the social types mechanism, I argue that the social incentives mechanism may underlie reciprocity in humans.


Investigation of age-related changes in brain activity during the divalent task-switching paradigm using functional MRI.
This study compared the brain activation of young and older subjects during the use of the task-switching paradigm (TSP) at various task speeds to examine the relationship between task load and brain activation. Specifically, it attempted to examine whether the task load-dependent BOLD response gradient is a useful tool for functional magnetic resonance imaging-based assessments of age-related changes in cognitive function. We predicted that the extent of the activation of the brain regions responsible for task-set reconfiguration and the inhibition of task switching functions induced during the performance of a TSP-based task would vary according to age. Task difficulty was controlled by altering the inter-stimulus interval. Although similar brain regions were activated in both age groups, significant differences in the extent of the activation were detected between the young and older groups. In particular, some regions were activated in the older group, but not the young group. This study indicated that TSP-based task performance-induced activation of the brain regions linked to executive function increases with age and that the degree and pattern of such activation depend on the content and difficulty of the task being performed. This indicates that the age- and task difficulty-dependent augmentation of brain activation varies between brain regions.


A Critical Analysis of the Scientific and Commercial Rationales for the De Novo Synthesis of Horsepox Virus.
This article evaluates the scientific and commercial rationales for the synthesis of horsepox virus. I find that the claimed benefits of using horsepox virus as a smallpox vaccine rest on a weak scientific foundation and an even weaker business case that this project will lead to a licensed medical countermeasure. The combination of questionable benefits and known risks of this dual use research raises serious questions about the wisdom of undertaking research that could be used to recreate variola virus. This analysis also raises important questions about the propriety of a private company sponsoring such dual use research without appropriate oversight and highlights an important gap in United States dual use research regulations.


Transforming growth factor beta 1 enhances expression of 50 kDa protein related to 2'-5' oligoadenylate synthetase in human sperm cells.
Human cellular polypeptide factors, namely interferon-alpha, interferon-gamma transforming growth factor (TGF)-alpha, and TGF-beta 1, were analyzed for their effect on motility of human sperm cells. Both interferons caused an inhibition of sperm cell motility due to direct cytotoxic effects without inducing 2'-5' oligoadenylate [2-5(A)]synthetase activity. TGF-alpha affected neither motility nor the levels of 2-5(A) synthetase in sperm cells. TGF-beta 1 had no affect on sperm motility, yet it caused an induction of 2-5(A)synthetase activity. Western immunoblot analysis of TGF-beta 1-treated sperm indicated an enhancement of a 50 kDa protein. Metabolic labeling of sperm cells revealed biosynthesis of one major protein of 50 kDa and at least five minor proteins in the range of 30-92 kDa; the level of 50 kDa protein increased after treatment with TGF-beta 1. The treatment of sperm cells with TGF-beta 1 did not affect their penetration in zona-free hamster eggs (SPA). These results indicate that TGF-beta 1 enhances expression of a 50 kDa protein related to 2-5(A) synthetase in human sperm cells along with other minor proteins, and this increase does not affect sperm motility and SPA.


Radiographic evaluation of native anterior cruciate ligament attachments and graft placement for reconstruction. A cadaveric study.
We examined seven cadaveric knees to determine the radiographic location of the native anterior cruciate ligament insertion sites as well as the location of tunnels used in anterior cruciate ligament reconstruction. Posteroanterior and lateral views at several flexion angles were taken with radiopaque markers around the insertions of the native anterior cruciate ligament and subsequent reconstruction tunnels. The femoral insertion was best seen on the 60 degrees notch view. On the lateral view, the femoral tunnel was easily seen as it crossed the roof of the intercondylar notch; however, because of the angle of the tunnel, the actual entrance into the knee may be well distal and anterior to this location. The tibial insertion and tunnel were easily seen at any flexion angle. The center of the insertion was 40% of the tibial diameter from the anterior margin. The lateral view in extension allowed determination of the tibial tunnel's location in relation to the intercondylar notch roof, but by itself did not allow accurate determination of the femoral tunnel's position. Notch and extension lateral radiographs together provided sufficient information for evaluation of anterior cruciate ligament graft position in a convenient, cost-effective format. Neither view by itself provides enough information to evaluate the position of the graft.


Counter-ion binding by bile acid solutions.
The binding of Ca2+ to micelles of glycine and taurine bile acid conjugates was studied using a Ca2+-specific electrode. An investigation of the effect of buffer concentration, pH, added electrolyte and lecithin was also performed. The results indicate that the binding of Ca2+ to bile salt micelles is dependent on the number of hydroxyl groups on the steroid nucleus and on the nature of the head conjugating group, namely, glycine or taurine. It is speculated that the binding of Ca2+ to bile salt micelles may act as one mechanism to lower Ca2+ activity in bile and, thus, reduce its tendency to precipitate as insoluble calcium salts and further growth into gallstones.


A search filter for increasing the retrieval of animal studies in Embase.
Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments.


Expression and function of Qa-2 major histocompatibility complex class I molecules in transgenic mice.
Qa-2 molecules are weak transplantation antigens encoded by class I genes of the major histocompatibility complex. When expressed in transgenic CBA mice, Qa-2 molecules provoke rapid rejection of skin grafts and strong, Qa-2 specific, cytotoxic T-cell responses. Efficient rejection of skin grafts from Qa-2 transgenic mice takes place when Qa-2 molecules are attached to the cell membrane with a glycophosphatidyl anchor or by a transmembrane protein domain, except that rejection times are slightly longer in the former case. These results demonstrate that Qa-2 molecules can behave as major transplantation antigens, as do closely related H-2 molecules. Failure of Qa-2 molecules to provoke strong T-cell responses in non-transgenic mice is probably due to the very low level of expression of Qa-2 molecules in skin keratinocytes from such mice since these cells express increased levels of Qa-2 molecules in all Qa-2 transgenic mice.


BACE1 gene promoter is differentially regulated: detection of a novel promoter region for its cell type-specific regulation.
The amyloid-beta (Abeta) peptide, the proteolytic fragment of Abeta precursor protein (APP), aggregates and forms neuritic plaques, a major hallmark of Alzheimer's disease (AD). The limiting step in generating the Abeta peptide from APP is cleavage by the beta-secretase enzyme, BACE1. Regulation of the BACE1 gene is likely to play an important role in AD etiology and treatment. We therefore studied the activity of a 4.1-kb 5'-flanking region (-3765/+364, +1 being the transcription start site) of the BACE1 gene, both in 5'- and 3'-deletion series and through Northern blotting. We show that the BACE1 promoter has regulatory activity throughout the 4.1-kb length, both positive and negative, and that this activity can be quantitatively modeled according to promoter sequence length, with the specific model depending on the presence of negative regulatory elements as the 5'- most portion of the sequence. We also examined a previously identified 141-bp proximal fragment (+224/+364) of the BACE1 promoter and two constituent (91- and 50-bp) subfragments. We report that the 91-bp fragment (+224/+314) is the most likely seat of neuronal expression of the BACE1 gene and that it is the portion of the 141-bp fragment that accounts for observed DNA-protein interactions in brain extracts. The 50-bp fragment (+315/+364), which showed significant reporter gene activity from the empty vector, binds nuclear proteins in a cell type-specific manner and contains the AP2 site as shown by the electrophoretic mobility shift assay. Overall, the 141-bp fragment had no strong matches within GenBank, and the 91-bp fragment is predicted to have several potential stem-loop sites. Taken together, BACE1 gene promoter activity is differentially regulated, and the 91-bp fragment represents a novel promoter region for cell type-specific regulation. This fragment might be a useful target to regulate BACE1 expression leading to Abeta production and to understand the neuropathogenesis of AD.


Leucocyte ascorbic acid concentration and plasma ascorbic acid levels in children with various infections.
In this study leucocyte ascorbic acid concentrations and plasma ascorbic acid levels were measured simultaneously and correlation between these two variables was sought in various bacterial and viral infections. A total of 258 patients were studied. The control group consisted of 21 healthy children in the same age group. Except for scarlet fever no significant differences were observed between the patients' leucocyte ascorbic acid levels during and after the infections and also no differences were observed in leucocyte ascorbic acid levels between control's and patient's. However plasma ascorbic acid values were significantly decreased during infection in all patients. During infection ascorbic acid is utilized rapidly, and our findings seem to indicate that there is transfer of ascorbic acid from plasma to leucocytes in order to keep the leucocyte ascorbic acid levels within normal limits.


A review of topical corrosive black salve.
Black salve is a compound derived from various inert ingredients, but it can be transformed into a corrosive ointment by the addition of bloodroot (Sanguinaria canadensis) or zinc chloride. Black salve products have been advertised as a natural remedy for many ailments, ranging from bee stings to skin cancer. This article reviews the current literature surrounding this compound, which in its corrosive form can be dangerous for use without medical supervision. Patients should be educated about the lack of objective evidence supporting the clinical efficacy of black salve as a skin cancer treatment, as well as the possible cosmetic defects resulting from tissue necrosis secondary to the effects of bloodroot and zinc chloride.


Phospholipid distributions in purple phototrophic bacteria and LH1-RC core complexes.
In contrast to plants, algae and cyanobacteria that contain glycolipids as the major lipid components in their photosynthetic membranes, phospholipids are the dominant lipids in the membranes of anoxygenic purple phototrophic bacteria. Although the phospholipid compositions in whole cells or membranes are known for a limited number of the purple bacteria, little is known about the phospholipids associated with individual photosynthetic complexes. In this study, we investigated the phospholipid distributions in both membranes and the light-harvesting 1-reaction center (LH1-RC) complexes purified from several purple sulfur and nonsulfur bacteria. 31P NMR was used for determining the phospholipid compositions and inductively coupled plasma atomic emission spectroscopy was used for measuring the total phosphorous contents. Combining these two techniques, we could determine the numbers of specific phospholipids in the purified LH1-RC complexes. A total of approximate 20-30 phospholipids per LH1-RC were detected as the tightly bound lipids in all species. The results revealed that while cardiolipin (CL) exists as a minor component in the membranes, it became the most abundant phospholipid in the purified core complexes and the sum of CL and phosphatidylglycerol accounted for more than two thirds of the total phospholipids for most species. Preferential association of these anionic phospholipids with the LH1-RC is discussed in the context of the recent high-resolution structure of this complex from Thermochromatium (Tch.) tepidum. The detergent lauryldimethylamine N-oxide was demonstrated to selectively remove phosphatidylethanolamine from the membrane of Tch. tepidum.


High resolution 3D gas-jet characterization.
We present a tomographic characterization of gas jets employed for high-intensity laser-plasma interaction experiments where the shape can be non-symmetrically. With a Mach-Zehnder interferometer we measured the phase shift for different directions through the neutral density distribution of the gas jet. From the recorded interferograms it is possible to retrieve 3-dimensional neutral density distributions by tomographic reconstruction based on the filtered back projections. We report on criteria for the smallest number of recorded interferograms as well as a comparison with the widely used phase retrieval based on an Abel inversion. As an example for the performance of our approach, we present the characterization of nozzles with rectangular openings or gas jets with shock waves. With our setup we obtained a spatial resolution of less than 60 μm for an Argon density as low as 2 × 10(17) cm(-3).


Protein tyrosine phosphatase receptor type delta (PTPRD) gene in an animal model of restless legs syndrome.
The pathophysiology of the restless legs syndrome (RLS) is related to dopaminergic dysfunction, reduced iron and variations in gene expression, such as the protein tyrosine phosphatase receptor type delta gene (PTPRD). Animal models could be key to achieving a mechanistic understanding of RLS and to facilitate efficient platforms for evaluating new therapeutics. Thus, the aim of this study was to evaluate the expression of PTPRD, of genes and proteins associated with RLS, the sleep patterns and the cardiovascular parameters in an animal model of RLS (spontaneously hypertensive rat [SHR]). Rats were divided into two groups: (i) Wistar-Kyoto and (ii) SHR. Cardiovascular parameters were assessed by tail plethysmography. Polysomnography was used to analyse the sleep pattern (24 h). For the PTPRD analyses, quantitative polymerase chain reaction (qPCR) and indirect enzyme-linked immunosorbent assay (ELISA) techniques were used. To evaluate the tyrosine hydroxylase enzyme, dopamine transporter (DAT) and type 2 dopaminergic receptor, qPCR and Western Blotting techniques were used. For the quantification of iron, ferritin and transferrin, the ELISA method was used. SHRs had higher blood pressure, alterations in sleep pattern, lower expression of protein content of PTPRD, lower expression of DAT, and lower serum concentrations of ferritin. These data suggest that the behavioural, physiological, and molecular changes observed in SHRs provide a useful animal model of RLS, reinforcing the importance of this strain as an animal model of this sleep disorder.


The nucleosome DNA entry-exit site is important for transcription termination and prevention of pervasive transcription.
Compared to other stages in the RNA polymerase II transcription cycle, the role of chromatin in transcription termination is poorly understood. We performed a genetic screen in Saccharomyces cerevisiae to identify histone mutants that exhibit transcriptional readthrough of terminators. Amino acid substitutions identified by the screen map to the nucleosome DNA entry-exit site. The strongest H3 mutants revealed widespread genomic changes, including increased sense-strand transcription upstream and downstream of genes, increased antisense transcription overlapping gene bodies, and reduced nucleosome occupancy particularly at the 3' ends of genes. Replacement of the native sequence downstream of a gene with a sequence that increases nucleosome occupancy in vivo reduced readthrough transcription and suppressed the effect of a DNA entry-exit site substitution. Our results suggest that nucleosomes can facilitate termination by serving as a barrier to transcription and highlight the importance of the DNA entry-exit site in broadly maintaining the integrity of the transcriptome.


The structure of the epididymis of the giant rat (Cricetomys gambianus, Waterhouse): histological, histochemical and microstereological studies.
The structure of the ductus epididymidis of the African giant rat (Cricetomys gambianus, Waterhouse) was studied by means of histological (paraffin and plastic-embedded tissues) and histochemical techniques. Five distinct zones (I-V) were detected along the epididymal duct on the basis of epithelial height and cytological composition and structure. The so-called apical cells, which have been observed in some species of animals, were not seen in the initial segment of the duct. Clear or light cells were present in the epithelium of the terminal segment, thus making the giant rat the third species in which this cell has been found, after the laboratory rat and the hamster. A large number of intra-epithelial lymphocytes and macrophage-like cells was commonly observed in the epithelium throughout the duct; the latter were strongly PAS-positive while the former tended to increase in number caudally. A microstereological study of the epididymis showed that Zones I (initial segment) and II contained a significantly (P less than 0.001) higher proportion of epithelium and a relatively greater (P less than 0.001) proportion of blood vessels in the interductal connective tissue than the more caudal segments of the epididymis which possessed a significantly (P less than 0.01) higher proportion of interductal connective tissue.


Organizing for communication and integration.
Using the departmental philosophy as its foundation, an integrated organizational model was designed for a nursing department. This patient-centered model was implemented to streamline operations, focus resources, and provide a professional practice environment for nursing staff. The "molecule" is used as a teaching tool and organizational framework, with applications ranging from orientation of new staff to management of daily operations.


Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system.
Crystals of phosphorylated JAK1 kinase domain were initially generated in complex with nucleotide (ADP) and magnesium. The tightly bound Mg2+-ADP at the ATP-binding site proved recalcitrant to ligand displacement. Addition of a molar excess of EDTA helped to dislodge the divalent metal ion, promoting the release of ADP and allowing facile exchange with ATP-competitive small-molecule ligands. Many kinases require the presence of a stabilizing ligand in the ATP site for crystallization. This procedure could be useful for developing co-crystallization systems with an exchangeable ligand to enable structure-based drug design of other protein kinases.


[Early infantile epileptic encephalopathy].
Early infantile epileptic encephalopathy (EIEE) with burst-suppression (Ohtaharas syndrome) is a rare type of epileptic encephalopathy in infancy and represents the earliest type of age-related symptomatic generalised epilepsy. We present 4 cases of EIEE fulfilling the classic diagnostic criteria, excluding the cases with segmentary and erratic myoclonic, characteristic features of Early Myoclonic Encephalopathy. All the patients were females. Pregnancy and delivery were normal and no other cases were observed in the families. One of the patients had a normal twin brother. Seizures began in all the cases before the 10th day of life. The initial EEG showed burst-suppression pattern, lasting for an average of 2.3 months of age (1.5-4 months). Seizures were initially resistant to therapy, although 2 cases showed partial response. None of the patients evolved to West syndrome. A case died at 5 months of age. No etiologic factors were found in two cases, but hemimegalencephaly was detected in the other two patients; in one of them seizures disappeared after corticectomy. We believe EIEE constitutes a type of epileptic encephalopaty which can be distinguished from other types of early onset epilepsy and should be included in the International Classification of Epilepsies with the West and Lennox-Gastaut syndromes.


Jamais vu episodes in relationship to baclofen treatment: a case report.
A 37-year-old man presented with new onset jamais vu episodes. Jamais vu is a mental state characterized by a sense of unfamiliarity in a familiar situation. The patient's episodes of jamais vu were unrelated to any known factor other than his use of baclofen. The episodes, which occurred as each baclofen dose wore off, resolved after the baclofen dose that triggered it was discontinued. The patient has had no recurrence of jamais vu states after discontinuation of his baclofen. This is the first known case report of jamais vu episodes caused by baclofen. Although jamais vu episodes can occur in healthy persons, they are known to occur more frequently in persons with epilepsy, fatigue, psychologic states, or intoxications. This case suggests that medications should be considered as a possible cause of jamais vu episodes.


Effects of Organic Phosphorus on Methylotrophic Methanogenesis in Coastal Lagoon Sediments With Seagrass (Zostera marina) Colonization.
Methanogens are the major contributors of greenhouse gas methane and play significant roles in the degradation and transformation of organic matter. These organisms are particularly abundant in Swan Lake, which is a shallow lagoon located in Rongcheng Bay, Yellow Sea, northern China, where eutrophication from overfertilization commonly results in anoxic environments. High organic phosphorus content is a key component of the total phosphorus in Swan Lake and is possibly a key factor affecting the eutrophication and carbon and nitrogen cycling in Swan Lake. The effects of organic phosphorus on eutrophication have been well-studied with respect to bacteria, such as cyanobacteria, unlike the effects of organic phosphorus on methanogenesis. In this study, different sediment layer samples of seagrass-vegetated and unvegetated areas in Swan Lake were investigated to understand the effects of organic phosphorus on methylotrophic methanogenesis. The results showed that phytate phosphorus significantly promoted methane production in the deepest sediment layer of vegetated regions but suppressed it in unvegetated regions. Amplicon sequencing revealed that methylotrophic Methanococcoides actively dominated in all enrichment samples from both regions with additions of trimethylamine or phytate phosphorus, whereas methylotrophic Methanolobus and Methanosarcina predominated in the enrichments obtained from vegetated and unvegetated sediments, respectively. These results prompted further study of the effects of phytate phosphorus on two methanogen isolates, Methanolobus psychrophilus, a type strain, Methanosarcina mazei, an isolate from Swan Lake sediments. Cultivation experiments showed that phytate phosphorus could inhibit methane production by M. psychrophilus but promote methane production by M. mazei. These culture-based studies revealed the effects of organic phosphorus on methylotrophic methanogenesis in coastal lagoon sediments and improves our understanding of the mechanisms of organic carbon cycling leading to methanogenesis mediated by organic phosphorus dynamics in coastal wetlands.


New aspects in performing interventional techniques for chronic pain.
We will evaluate the usefulness of the new intrathecal analgesic ziconotide in palliative care medicine. We will also examine the place and efficacy of neurolytic celiac plexus blockade in patients suffering from malignancy in the upper abdomen, after introducing better localization methods of the celiac plexus. The analgesic effects of intrathecally administered ziconotide have been studied in patients suffering from pain due to AIDS or cancer. The results show a moderate to complete pain relief, significantly better than in placebo groups. However, safety studies show a high incidence of side effects. The technique of neurolytic celiac plexus blocks is refined by endoscopic ultrasound techniques. The place of ziconotide in palliative care is doubtful due to unpredictable and sometimes long-lasting side effects. Real evidence on the efficacy and duration of neurolytic celiac plexus blocks for relief of pancreatic cancer pain is still not available. Future studies will need to be performed applying validated measurement instruments and assessing the patient's impression of the procedure's demands in terms of physical and mental tolerance.


Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial.
To investigate the efficacy and safety of levodopa plus benserazide in the treatment of restless legs syndrome (RLS), in terms of the frequency of periodic limb movements (PLMs), objective and subjective criteria of sleep, onset of action, and withdrawal effects. A randomized, double-blind, placebo-controlled, multicenter, crossover trial, with two 4-week treatment periods. Outpatient units of three specialist centers in Germany. Eligible patients had to fulfill the diagnostic criteria of the International RLS Study Group and have sleep disturbances and PLMs during sleep shown on polysomnography at screening. Thirty-five patients were recruited, of whom 32 (13 men, 19 women) completed the study. Patients received a single dose of standard-release levodopa/benserazide 100/25 mg or placebo at bedtime each night for 4 weeks, before crossing over to receive the alternative treatment for a further 4 weeks; the dose could be doubled if required. The average dosages were 159 +/- 31 mg of levodopa and 1.56 +/- 0.29 capsules of placebo. Levodopa/benserazide significantly reduced the number of PLMs per hour (p<0.0001), increased the time in bed without limb movements (p<0.0001), and improved subjective quality of sleep (p=0.0004). The onset of action was rapid after the first dose, and full efficacy was achieved within the first few days of therapy; these improvements disappeared immediately when treatment was discontinued. Levodopa/benserazide treatment was well tolerated and safe. Levodopa/benserazide is effective and safe in the treatment of RLS. Objective and subjective measures of sleep improved rapidly after the first dose. RLS symptoms recurred immediately after treatment was discontinued.


An Onsite Fitness Facility and Integrative Wellness Program Positively Impacted Health-Related Outcomes Among Teachers and Staff at an Urban Elementary/Middle School.
Given the large number of obesity-focused studies conducted in schools, there is a surprising lack of data regarding teacher workplace health behaviors in the United States. To determine the feasibility and effectiveness of an onsite fitness facility with a structured integrative wellness program to improve health-related outcomes among teachers and staff at an urban elementary/middle school. A 2-year mixed-methods analysis using Patient-Reported Outcomes Measurement Information System (PROMIS) measures and qualitative interviews included 39 teachers and staff employed at an urban elementary/middle school in Baltimore, Maryland. The fitness facility was dedicated exclusively to teachers and staff and the integrative wellness program included group exercise classes, yoga, mindfulness, and nutrition competitions. T tests were used to compare quantitative outcomes at baseline, the end of year 1, and the end of year 2. Compared to baseline, at year 1, there was a significant improvement in the PROMIS Sleep Disturbance score. From baseline to end of year 2, there were significant increases in the PROMIS Global Physical Health as well as significant decreases in Sleep Disturbances, Fatigue, and Social Isolation. Qualitative interviews conducted at the end of year 1 indicated that teachers who used the facility felt that it improved their mood, increased their energy, motivated them to eat healthily, and gave them opportunities to socialize with their colleagues in new ways. This impact was further enhanced in year 2. An onsite fitness facility with an integrative wellness program may improve health-related outcomes among urban elementary school teachers and staff, with the greatest benefits seen after 2 years of implementation.


Community-wide outbreak of enteroviral illness caused by echovirus 30: a cross-sectional survey and a case-control study.
In June, 1997, 21 children from a single community in Germany were hospitalized with aseptic meningitis. An epidemiologic investigation was conducted to determine the extent of the outbreak and risk factors for illness. The extent of the outbreak was assessed with a cross-sectional survey of every 10th child listed in the town register among the 2240 town children < 16 years old. A case-control study determined risk factors for illness. Sixty-two cases were identified through the cross-sectional survey from hospitalized persons and from persons seen by local physicians. Controls were 114 asymptomatic persons identified from the cross-sectional survey. The overall attack rate was 16%, with the highest attack rates (24%) among the 6- to 8-year olds. Onsets occurred during a 37-day period. Among the 2240 town children <16 years of age, an estimated 353 met the case definition for enteroviral illness, 168 visited a doctor and 21 were hospitalized. Data from the case-control study indicated that contact with an ill household member [odds ratio (OR) = 6.3; 95% confidence interval (CI) 2.6 to 15.5], day-care attendance (OR = 2.6; 95% CI 1.1 to 6.2) and playground use, either two to three times per week (OR = 3.7; 95% CI 1.3 to 10.2) or daily (OR = 4.3; 95% CI 1.6 to 11.3), were risk factors for illness. Echovirus 30 caused substantial morbidity during this community outbreak caused by person-to-person spread. Household contacts, day-care centers and playgrounds were prominent risk factors for transmission.


Cholesterol oxidase senses subtle changes in lipid bilayer structure.
We investigated the dependence of cholesterol oxidase catalytic activity and membrane affinity on lipid structure in model membrane bilayers. The binding affinities of cholesterol oxidase to 100-nm unilamellar vesicles composed of mixtures of DOPC or DPPC and cholesterol are not sensitive to cholesterol mole fraction if the phase of the membrane is in a fluid state. When the membrane is in a solid-ordered state, the binding affinity of cholesterol oxidase increases approximately 10-fold. The second-order rate constants (kcat*/Km*) for different lipid mixtures show a 2-fold substrate specificity for cholesterol in the l(d) phase of high cholesterol chemical activity over cholesterol in the l(o) phase. Moreover, the enzyme is 2-fold more specific for cholesterol in the l(o) phase than in the s(o) phase. Likewise, there is 2-fold substrate specificity for the high cholesterol chemical activity l(d) phase over the low chemical activity l(d) phase. The specificities for the l(d) phase of low cholesterol chemical activity and the l(o) phase are the same. These data indicate that the more ordered the lipid cholesterol structure in the bilayer, the lower the catalytic rate. However, under all of the conditions investigated, the enzyme is never saturated with substrate. The enzymatic activity directly reflects the facility with which cholesterol can move out of the membrane, whether changes in cholesterol transfer facility are due to phase changes or more localized changes in packing. We conclude that the activity of cholesterol oxidase is directly and sensitively dependent on the physical properties of the membrane in which its substrate is bound.


[Institutional scabies].
We describe an outbreak of scabies affecting 13 patients and staff members in a geriatric ward. The difficulties of diagnosis and treatment are discussed, and it is suggested that the local hygiene unit should be involved immediately if institutional scabies is suspected.


Peroxisomal CuAOζ and its product H2O2 regulate the distribution of auxin and IBA-dependent lateral root development in Arabidopsis.
Root system architecture depends on endogenous and environmental signals, including polar transport of the phytohormone auxin, reactive oxygen species (ROS), nutrient availability, and stresses. In our study, we describe a novel Arabidopsis thaliana peroxisome-localized copper amine oxidase ζ (CuAOζ), which is highly expressed in cortical cells, and the ROS derived from CuAOζ are essential for lateral root (LR) development. Loss of CuAOζ results in retarded auxin-induced ROS generation, PINFORMED2 (PIN2)-mediated auxin transport, and LR development in response to added indole-3-butyric acid. Auxins enhance CuAOζ protein levels and their cellular translocation toward the plasma membrane in the cortex. CuAOζ interacts physically with PEROXINS5 via an N-terminal signal tag, Ser-Lys-Leu, and is transported into the peroxisome upon this interaction, which is required for the functions of CuAOζ in the auxin response. Together, our results suggest a peroxisomal ROS-based auxin signaling pathway involving spatiotemporal-dependent CuAOζ functional regulation of PIN2 homeostasis, auxin distribution, and LR development.


A split-root technique for measuring root water potential.
Water encounters various resistances in moving along a path of decreasing potential energy from the soil through the plant to the atmosphere. The reported relative magnitudes of these pathway resistances vary widely and often these results are conflicting. One reason for such inconsistency is the difficulty in measuring the potential drop across various segments of the soil-plant-atmosphere continuum. The measurement of water potentials at the soil-root interface and in the root xylem of a transpiring plant remains a challenging problem.In the divided root experiment reported here, the measured water potential of an enclosed, nonabsorbing branch of the root system of young corn (Bonanza) plants to infer the water potential of the remaining roots growing in soil was used. The selected root branch of the seedling was grown in a specially constructed Teflon test tube into which a screen-enclosed thermocouple psychrometer was inserted and sealed to monitor the root's water potential. The root and its surrounding atmosphere were assumed to be in vapor equilibrium.


Energy and protein requirements for maintenance of dairy goats during pregnancy and their efficiencies of use.
It has been suggested that maintenance requirements are similar among animals of different physiological stages; however, important physiological changes occur in the maternal body during pregnancy. Therefore, the aim of this study was to determine the energy and protein requirements for the maintenance of pregnant dairy goats and to estimate their efficiency of energy and protein utilization for maintenance and pregnancy. We used 66 multiparous pregnant goats having 49.0 ± 1.59 kg initial BW (around the third or fourth parturition) arranged in a randomized block design with a 3 × 3 factorial scheme including slaughter at different days of pregnancy (DOP; 80, 110, and 140 d) and feed restriction (0, 20, and 40% feed restriction). The comparative slaughter technique was used to estimate energy and protein maintenance requirements. Goats slaughtered at 140 DOP were subjected to digestibility trials at around 80, 110, and 140 DOP to estimate diet metabolizability and N balance (NBAL). Metabolizability decreased with feed restriction and was 63.3 ± 2.16, 55.7 ± 2.35, and 58.2 ± 2.30% at 0, 20, and 40% of feed restriction, respectively ( < 0.01). There was no effect of DOP on NE or the requirements of ME for maintenance (ME), which were 197 and 315 kJ/kg empty body weight (EBW), respectively, and the efficiency of ME utilization for maintenance (k) was 0.63. Similarly, DOP did not affect thedaily net protein requirements for maintenance (NP) estimated using the comparative slaughter technique (1.38 ± 0.512 g/kg EBW; = 0.003) or the NP estimated using NBAL (2.49 ± 0.594 g/kg EBW; < 0.01). The MP requirement for maintenance (MP) estimated using the comparative slaughter technique was not affected by DOP and was 3.22 g MP/kg EBW ( < 0.01). The efficiency of MP utilization for maintenance (k) was 0.43. The efficiency of ME utilization for pregnancy (k) increased with the progress of pregnancy and was 0.058, 0.10, and 0.19 at 80, 110, and 140 DOP, respectively. Similarly, the efficiency of MP utilization for pregnancy (k) increased with DOP and was 0.12, 0.21, and 0.43 at 80, 110, and 140 DOP, respectively. There was no evidence that pregnancy affected NE, ME, NP, and MP or k and k, which were also unaffected by DOP. However, k and k increased with pregnancy progress as a response to the physiological changes that pregnant females are subjected to.


Influence of systolic pressure profile on rate of left ventricular pressure fall.
We examined the influence of the systolic left ventricular pressure (LVP) waveform on the rate of isovolumetric LVP fall, as assessed by the time constant tau. Seven open-chest dogs were instrumented with a micromanometer in the left ventricle, with segment length gauges in the anterior and posterior midwall of the left ventricle, and with a balloon-tipped catheter in the proximal aorta. The intra-aortic balloon was inflated before the onset of ejection (early) or during midejection (late) to produce timed and graded increases in peak LVP of 2-20 mmHg. The rate of LVP fall slowed significantly more with late than with early increases in LVP (tau increased 1.5 +/- 0.5 vs. 0.5 +/- 0.3%/mmHg increase in peak LVP, respectively, P less than 0.001). For a similar increase in peak LVP, there was a progressively greater increase in tau when the timing of balloon inflation was progressively delayed from early to late ejection (in 10-ms increments). The differential effect of early vs. late pressure increases on tau was not related to regional differences in segment length behavior nor to an increase in regional nonuniformity between anterior and posterior sites. We conclude that under the experimental conditions of an intact, ejecting left ventricle, the systolic pressure profile is an important determinant of the rate of pressure fall. The rate of LVP fall slows in direct proportion to the magnitude of increase in systolic pressure. The sensitivity to systolic load increases progressively throughout the ejection period, so that the rate of LVP fall slows significantly more with late than with early pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS)


Ability of human plasma to inhibit prostaglandin F2 alpha in asthma.
Human plasma has been reported to inhibit the conversion of arachidonic acid into prostaglandin (PG) E2 and PGF2 alpha. In the present study the plasma inhibitory activity was determined in three groups (16 each) of plasma obtained from normal healthy volunteers, treated asthmatics and untreated asthmatic patients. The result showed that plasma from all three groups were equally effective in inhibiting the biosynthesis of PGE2. Plasma of normal volunteers and treated asthmatics also inhibited PGF2 alpha biosynthesis. In contrast the plasma obtained from untreated asthmatics was considerably less active in inhibiting the biosynthesis of PGF2 alpha than plasma from the other two groups.


Uptake of the neurotoxin 1-methyl-4-phenylpyridine (MPP+) by mitochondria and its relation to the inhibition of the mitochondrial oxidation of NAD+-linked substrates by MPP+.
1-methyl-4-phenylpyridine (MPP+), a major product of the oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been postulated to be the compound responsible for destruction of nigrostriatal neurons in man and primates and for inhibition of mitochondrial NADH oxidation which leads to cell death. We have confirmed that 0.5 mM MPP+ inhibits extensively the oxidation of NAD+-linked substrates in intact liver mitochondria in State 3 and after uncoupling, while succinate oxidation is unaffected. However, in inverted mitochondria, inner membrane preparations, and Complex I NADH oxidation is not significantly affected at this concentration of MPP+, nor are malate and glutamate dehydrogenases or the carriers of these substrates inhibited. We report here the discovery of an uptake system for MPP+ in mitochondria which is greatly potentiated by the presence of malate plus glutamate and inhibited by respiratory inhibitors, suggesting an energy-dependent carrier. A 40-fold concentration of MPP+ in the mitochondria occurs in ten minutes. This might account for the inhibition of malate and glutamate oxidation in intact mitochondria.


Recovery of susceptibility to audiogenic seizure in mice.
The applicability of the auditory fatigue and anoxia hypotheses for the refractory period observed after sound-induced seizure was examined in SJL/J mice. Duration of auditory stimulation was varied independent of attainment of clonic seizure activity by use of an acoustic interruption technique. Duration of the recovery period affected the pattern of preconvulsive running. Furthermore, the motor asymmetries exhibited during clonus remained consistent across tests. Because duration of acoustic stimulation and attainment of clonus did not affect recovery rate, we conclude that neither the auditory fatigue nor the anoxia hypothesis provides a complete account for the refractory period after audiogenic seizure. We suggest that an inhibitory process, activated before clonus occurs and perhaps linked to depletion of excitatory amino acids in the inferior colliculus, may also be involved.


Comparative Study of Crystallization, Mechanical Properties, and In Vitro Cytotoxicity of Nanocomposites at Low Filler Loadings of Hydroxyapatite for Bone-Tissue Engineering Based on Poly(l-lactic acid)/Cyclo Olefin Copolymer.
A poly(l-lactic acid)/nanohydroxyapatite (PLLA/nHA) scaffold works as a bioactive, osteoconductive scaffold for bone-tissue engineering, but its low degradation rate limits embedded HA in PLLA to efficiently interact with body fluids. In this work, nano-hydroxyapatite (nHA) was added in lower filler loadings (1, 5, 10, and 20 wt%) in a poly(l-lactic acid)/cyclo olefin copolymer10 wt% (PLLA/COC10) blend to obtain novel poly(l-lactic acid)/cyclo olefin copolymer/nanohydroxyapatite (PLLA/COC10-nHA) scaffolds for bone-tissue regeneration and repair. Furthermore, the structure-activity relationship of PLLA/COC10-nHA (ternary system) nanocomposites in comparison with PLLA/nHA (binary system) nanocomposites was systematically studied. Nanocomposites were evaluated for structural (morphology, crystallization), thermomechanical properties, antibacterial potential, and cytocompatibility for bone-tissue engineering applications. Scanning electron microscope images revealed that PLLA/COC10-nHA had uniform morphology and dispersion of nanoparticles up to 10% of HA, and the overall nHA dispersion in matrix was better in PLLA/COC10-nHA as compared to PLLA/nHA. Fourier transformation infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC) studies confirmed miscibility and transformation of the α-crystal form of PLLA to the ά-crystal form by the addition of nHA in all nanocomposites. The degree of crystallinity (%) in the case of PLLA/COC10-nHA 10 wt% was 114% higher than pure PLLA/COC10 and 128% higher than pristine PLLA, indicating COC and nHA are acting as nucleating agents in the PLLA/COC10-nHA nanocomposites, causing an increase in the degree of crystallinity (%). Moreover, PLLA/COC10-nHA exhibited 140 to 240% (1-20 wt% HA) enhanced mechanical properties in terms of ductility as compared to PLLA/nHA. Antibacterial activity results showed that 10 wt% HA in PLLA/COC10-nHA showed substantial activity against P. aeruginosa, S. aureus, and L. monocytogenes. In vitro cytocompatibility of PLLA/COC10 and PLLA nanocomposites with nHA osteoprogenitor cells (MC3T3-E1) and bone mesenchymal stem cells (BMSC) was evaluated. Both cell lines showed two- to three-fold enhancement in cell viability and 10- to 30-fold in proliferation upon culture on PLLA/COC10-nHA as compared to PLLA/nHA composites. It was observed that the ternary system PLLA/COC10-nHA had good dispersion and interfacial interaction resulting in improved thermomechanical and enhanced osteoconductive properties as compared to PLLA/nHA.


Both decreased and increased heart rate variability on the standard 10-second electrocardiogram predict cardiac mortality in the elderly: the Rotterdam Study.
Decreased heart rate variability has been associated with an adverse prognosis in patients after myocardial infarction. Studies carried out in the population at large show contradictory results. The authors examined the association between heart rate variability on a standard 10-second electrocardiogram and cardiac and all-cause mortality in the Rotterdam Study, a population-based cohort study of men and women aged > or =55 years, using data collected between 1990 and 1996 (mean follow-up = 4 years). Heart rate variability, taken as the standard deviation of normal R-R intervals (SDNN), was computed by means of the Modular ECG Analysis System. After exclusion of subjects with arrhythmia and those with fewer than six normal R-R intervals, the study population consisted of 2,088 men and 3,184 women. Cox's proportional hazards model was used to examine the age- and sex-adjusted risk for cardiac, noncardiac, and total mortality in relation to quartiles of SDNN, using the third quartile of SDNN as the reference category. Subjects in the lowest quartile of SDNN relative to those in the third quartile had an 80 percent age- and sex-adjusted increased risk for cardiac mortality (hazard ratio = 1.8; 95% confidence interval: 1.0, 3.2). Interestingly, for subjects in the highest quartile of SDNN, an even more pronounced risk for cardiac mortality was present (hazard ratio = 2.3; 95% confidence interval: 1.3, 4.0). Additional adjustment for possible confounders did not materially change the risk estimates. The authors conclude that heart rate variability measured on the standard 10-second electrocardiogram can be used to identify older men and women with an increased risk for cardiac mortality. In the elderly, increased heart rate variability is an even stronger indicator of cardiac mortality than decreased heart rate variability. Further studies are needed to confirm these findings and to elucidate their physiologic meaning.


Extensive chromosomal variation in a recently formed natural allopolyploid species, Tragopogon miscellus (Asteraceae).
Polyploidy, or whole genome duplication, has played a major role in the evolution of many eukaryotic lineages. Although the prevalence of polyploidy in plants is well documented, the molecular and cytological consequences are understood largely from newly formed polyploids (neopolyploids) that have been grown experimentally. Classical cytological and molecular cytogenetic studies both have shown that experimental neoallopolyploids often have meiotic irregularities, producing chromosomally variable gametes and progeny; however, little is known about the extent or duration of chromosomal variation in natural neoallopolyploid populations. We report the results of a molecular cytogenetic study on natural populations of a neoallopolyploid, Tragopogon miscellus, which formed multiple times in the past 80 y. Using genomic and fluorescence in situ hybridization, we uncovered massive and repeated patterns of chromosomal variation in all populations. No population was fixed for a particular karyotype; 76% of the individuals showed intergenomic translocations, and 69% were aneuploid for one or more chromosomes. Importantly, 85% of plants exhibiting aneuploidy still had the expected chromosome number, mostly through reciprocal monosomy-trisomy of homeologous chromosomes (1:3 copies) or nullisomy-tetrasomy (0:4 copies). The extensive chromosomal variation still present after ca. 40 generations in this biennial species suggests that substantial and prolonged chromosomal instability might be common in natural populations after whole genome duplication. A protracted period of genome instability in neoallopolyploids may increase opportunities for alterations to genome structure, losses of coding and noncoding DNA, and changes in gene expression.


Spectrum of Venus in the Violet and Near-Ultraviolet.
Recent observations of the spectrum of the planet Venus, with spectrographs of low and high dispersion at the Georgetown College Observatory, show that a wide, continuous absorption band is present in the violet and near-ultraviolet. The band begins near wavelength 4500 A and extends to the short-wavelength limit of our spectrograms near 3800 A. It is similar in structure to the strong absorption, reported by others, for gaseous nitrogen tetroxide.


Bilateral retinal hamartomas in neurofibromatosis type 2.
We report a case of bilateral retinal hamartomas in a child with neurofibromatosis type 2. This unique case demonstrates that a diversity of retinal changes can occur in this disease.


Outcomes of pregnancies complicated by hyperemesis gravidarum.
To evaluate maternal and fetal outcomes among women with hyperemesis gravidarum (HG). In a university hospital and a research and training hospital, a retrospective cohort study was conducted among women with singleton deliveries between 2003 and 2011. Maternal outcomes evaluated included gestational diabetes, pregnancy-induced hypertension, cesarean delivery. Neonatal outcomes also determined were 5-min Apgar score of less than 7, low birth weight, small for gestational age (SGA), preterm delivery, fetal sex, and stillbirth. There were no statistical differences in the mean of age, parity, the number of artificial pregnancy, and smoking between two groups. Infants from HG pregnancies manifested similar birth weight (3,121.5 ± 595.4 vs. 3,164 ± 664.5 g) and gestational age (38.1 ± 2.3 vs. 38.1 ± 2.6 weeks), relative to infants from the control group (p = 0.67 and 0.91, respectively). In addition, no statistical significant differences were found in the rates of SGA birth, preterm birth, gestational diabetes, pregnancy-induced hypertension, and adverse fetal outcome between two groups (p > 0.05). Cesarean delivery rates were similar in two groups (31.9% in hyperemesis group vs. 27% in control group, p = 0.49). Comparing the gender of the newborn baby and Apgar scores less than 7 at 5 min, there were no statistically significant differences between two groups (p = 0.16 and 0.42, respectively). Hyperemesis gravidarum is not associated with adverse pregnancy outcomes.


[Leptospirosis at the Clinic for Infectious Diseases in Novi Sad 1984-1993].
We examined the clinical picture and course of leptospiral infections in 50 patients treated at the Clinic during the period 1984-1993. Most patients were 11-20 years of age (9 years the youngest and 77 years the oldest, mean age being 25.16). The disease more often occurred in male patients, 44 (88%). There were 30 (60%) patients with gastrointestinal symptoms, while 21 (42%) had liver and kidney infections. Meningeal syndrome was established in 25 (50%) and serous meningitis in 13 (26%). Leptospiral infections represented average and serious infections with complications in 8 (16%) patients, successful treatment in 47 (94%) patients while 3 (6%) patients died due to hematorenal insufficiency.


Using a GIS to model interventions to strengthen the emergency referral system for maternal and newborn health in Ethiopia.
To show how GIS can be used by health planners to make informed decisions about interventions to increase access to emergency services. A combination of data sources, including the 2008 national Ethiopian baseline assessment for emergency obstetric and newborn care that covered 797 geo-coded health facilities, LandScan population data, and road network data, were used to model referral networks and catchment areas across 2 regions of Ethiopia. STATA and ArcGIS software extensions were used to model different scenarios for strengthening the referral system, defined by the structural inputs of transportation and communication, and upgrading facilities, to compare the increase in access to referral facilities. Approximately 70% of the population of Tigray and Amhara regions is served by facilities that are within a 2-hour transfer time to a hospital with obstetric surgery. By adding vehicles and communication capability, this percentage increased to 83%. In a second scenario, upgrading 7 strategically located facilities changed the configuration of the referral networks, and the percentage increased to 80%. By combining the 2 strategies, 90% of the population would be served by midlevel facilities within 2 hours of obstetric surgery. The mean travel time from midlevel facilities to surgical facilities would be reduced from 121 to 64 minutes in the scenario combining the 2 interventions. GIS mapping and modeling enable spatial and temporal analyses critical to understanding the population's access to health services and the emergency referral system. The provision of vehicles and communication and the upgrading of health centers to first level referral hospitals are short- and medium-term strategies that can rapidly increase access to lifesaving services.


Retrograde transport of neurotrophins from the eye to the brain in chick embryos: roles of the p75NTR and trkB receptors.
The receptors involved in retrograde transport of neurotrophins from the retina to the isthmo-optic nucleus (ION) of chick embryos were characterized using antibodies to the p75 neurotrophin receptor and trkB receptors. Survival of neurons in the ION has been shown previously to be regulated by target-derived trophic factors with survival promoted or inhibited by ocular injection of brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF), respectively. In the present paper, we show that during the period of target dependence, these neurons express trkB and p75 neurotrophin receptor but not trkA or trkC mRNAs. We also show that BDNF and NT-3 were transported efficiently at low doses, whereas NGF was transported significantly only at higher doses. The transport of BDNF and NT-3 was reduced by high concentrations of NGF or by antibodies to either trkB or the p75 neurotrophin receptor. Thus both receptors help mediate retrograde transport of these neurotrophins. Ocular injection of the comparatively specific trk inhibitor K252a did not reduce transport of exogenous BDNF, but did induce significant neuronal death in the ION, which could not be prevented by co-injection of BDNF. Thus, transport of BDNF alone does not generate a trophic signal at the cell body when axonal trkB is inactivated. In summary, our results indicate that both p75 neurotrophin and trkB receptors can mediate internalization and retrograde transport of BDNF, but activation of trkB seems to be essential for the survival-promoting actions of this neurotrophin.


Cu(4.35)Cd(1.65)As(16): the first polyarsenic compound in the Cu-Cd-As system.
The first polyarsenic compound in the Cu-Cd-As system was obtained by solid-state reaction of the elements and has a refined composition of Cu(4.35 (2))Cd(1.65 (2))As(16) (tetra-copper dicadmium hexa-deca-arsenide). It adopts the Cu(5)InP(16) structure type. The asymmetric unit consists of one Cu site, a split Cu/Cd site and four As sites. The polyanionic structure can be described as being composed of As(6) rings in chair conformations which are connected in the 1-, 2-, 4- and 5-positions. The resulting layers evolve along the c axis perpendicular to the ab plane. One Cu atom exhibits site symmetry 2 and is tetra-hedrally coordinated by four As atoms. The other Cu atom, representing the split site, and the corresponding Cd atom have different coordination spheres. While the Cu atom is tetra-hedrally coordinated by four As atoms, the Cd atom has a [3 + 1] coordination with a considerably longer Cd-As distance.


The Texas twist.
The accountable care organization is becoming the trendy new health care delivery model of the decade. Texas physicians may have an alternative, thanks to legislation passed in the special session of the legislature that ended in late June. Senate Bill 7 authorized physicians, hospitals, and other health care providers to create health care collaboratives, similar to ACOs, to allow traditional competitors to join forces to improve quality of care and lower overall costs.


[Isolation, identification and structural characterization of secondary metabolites from amarine sponge-derived rare actinobacterium Dermacoccus sp. X4].
We isolated and identified the symbiotic and adnascent microorganisms from an unidentified sponge collected from 10-meter-deep seawater of the Paracel Islands in China. A total of 16 strains were obtained and identified. Through bacteriostatic activity assay, one of the strains, Dermacoccus sp. X4, was found to effectively inhibit the growth of Staphylococcus aureus. Subsequently, its secondary metabolites were purified by silica gel partition, octadecylsilane (ODS) reverse phase, Sephadex™LH-20 size exclusion, and C18 reverse phase chromatography. Using liquid chromatography, mass spectrometry, and nuclear magnetic resonance, three of the purified compounds were structurally characterized to be one 3-(4-hydroxybenzyl) hexahydropyrrolo [1,2-a]pyrazine-1,4-dione and two indole acid glycerides. This is the first report about indole acid glyceride isolated from microbial secondary metabolites, enriching marine drug candidate resources.


HPLC analysis of amino acids in inborn errors of metabolism.
Analysis of amino acids in blood or urine is a valuable diagnostic tool in cases of suspected metabolic disorders. The presence of a characteristic pattern of elevated amino acids is very useful in the diagnosis of these rare disorders. The detection of an apparently normal pattern of amino acids is also helpful to the clinician since it will eliminate many inborn errors of metabolism from the list of potential disorders. Methodologies for amino acid analysis in physiological fluids range from the very simple thin layer chromatography to automated low pressure or high pressure chromatography. Low pressure chromatography using a Beckman analyzer or similar instrument is the most common methodology for physiological amino acid analysis. Chromatography (HPLC) systems for amino acid analysis of proteins are available that can be modified for use with physiological samples. Waters makes a system called Picotag(TM) and Applied Biosystems makes an automated analyzer. These HPLC systems have some advantages over LPLC systems, including lower equipment cost, less caustic buffer systems and improved separation of certain amino acids.


Soy allergy in atopic children.
Although soy is considered a major food allergen (along with milk, egg, peanut, fish, and wheat), the prevalence of soy allergy in the pediatric population is not well defined. To determine the prevalence of soy allergy in atopic children attending the Allergy Clinic at the Pediatric Department of Milan University. Seven hundred four patients with allergic signs and symptoms, aged 1 month to 18 years, were recruited between December, 1991 and April, 1992. The subjects with positive skin prick tests to soy were tested using a DBPCFC with powdered soy formula in fruit juice, and rice or corn flour as placebo. In children who refused the liquid challenge, capsules containing dehydrated soy flour or talcum powder as placebo were administered. An age-matched and sex-matched group of subjects with negative skin prick tests to soy were tested using an open challenge with soy formula. A positive skin prick test to soy was found in 148/704 patients (21%); 131 out of 148 children with positive skin prick test (group A) and 131 out of 556 children with negative skin prick test to soy (group B) were challenged with soy: 8/131 (6%) in group A had a positive soy challenge while no clinical reactions were observed in children in group B. A younger median age, a positive past and current personal history of cow milk allergy, and a previous history of soy allergy were found most often in children with positive soy skin prick test and positive soy challenge than in children with positive skin prick test and negative soy challenge. The eight soy-allergic children reacted to the soy challenge mostly with cutaneous and gastrointestinal symptoms; symptoms were immediate in six and late in two children. The eliciting dose of soy was very small in the immediate reaction; higher and repeated doses were necessary for the onset of late reactions. The prevalence of clinical soy allergy in our children with positive skin prick tests to soy is 6.1% (8/131), while none of 131 children with negative skin prick test to soy reacted to the challenge.


Plastic Surgeon Financial Compensation-Incentivization Models in Surgical Care Delivery: The Past, Present, and Future.
Surgeons are critical for the success of any health care enterprise. However, few studies have examined the potential impact of value-based care on surgeon compensation. This review presents value-based financial incentive models that will shape the future of surgeon compensation. The following incentivization models will be discussed: pay-for-reporting, pay-for-performance, pay-for-patient-safety, bundled payments, and pay-for-academic-productivity. Moreover, the authors suggest the application of the congruence model-a model developed to help business leaders understand the interplay of forces that shape the performance of their organizations-to determine surgeon compensation methods applicable in value-based care-centric environments. The application of research in organizational behavior can assist health care leaders in developing surgeon compensation models optimized for value-based care. Health care leaders can utilize the congruence model to determine total surgeon compensation, proportion of compensation that is short term versus long term, proportion of compensation that is fixed versus variable, and proportion of compensation based on seniority versus performance. This review provides a framework extensively studied by researchers in organizational behavior that can be utilized when designing surgeon financial compensation plans for any health care entity shifting toward value-based care.


Impact of partial mastoid obliteration on caloric vestibular function in canal wall down mastoidectomy.
To evaluate the influence of our technique of partial mastoid obliteration with autologous bone pâté covered by cartilage plates on vestibular stimulation. Twenty-six patients who were treated for recurrent chronic otitis media by revision canal wall down tympanomastoidectomy and subsequent partial obliteration were invited for follow-up; 18 patients agreed to a complete follow-up including vestibular testing. Patients received questionnaires for evaluating preoperative and postoperative symptoms associated with vertigo. Examination comprised otomicroscopy, pure-tone audiometry, and caloric testing. Mean follow-up was 6 years. Before surgery, 54% of the patients reported vertigo on caloric stimuli such as wind, water, or suction cleaning of the tympanomastoid cavity. In all patients, these symptoms were suspended after partial mastoid obliteration. The postoperative obliterated cavity volume averaged 3.1 ml. All cavities after surgery appeared completely epithelialized and dry. The postoperative caloric vestibular tests revealed an average nystagmus count of 46 beats per minute compared with 72 beats before surgery. Thus, the partial mastoid cavity obliteration led to a mean nystagmus reduction of 36% in our study group. Our technique of partially obliterating tympanomastoid cavities with autologous bone pâté being covered by cartilage plates results in small cavities with complete epithelialization of all surfaces. Furthermore, obliteration of mastoid cavities confers protection to the labyrinthine organ, thereby reducing postoperative vertigo on caloric stimulation.


Amino-acid residue association models for large scale protein-protein interaction prediction.
The computational prediction of protein-protein interactions (PPI) is an essential complement to direct experimental evidence. Traditional approaches rely on less available or computationally predicted surface properties, show database-specific performances and are computationally expensive for large-scale datasets. Several sensitivity and specificity issues remain. Here, we report a novel method based on 'Amino-acid Residue Associations' (ARA) among interacting proteins which utilizes the accurate and easily available primary sequence. Large scale PPI datasets for six model species (from E. coli to human) were studied. The ARA method shows up to 73%sensitivity and 78% specificity. Furthermore, the method performs remarkably well in terms of stability and generalizability. The performance of ARA method benchmarked against existing prediction techniques shows performance improvement upto 25%. Ability of ARA method to predict PPI across species and across databases is also demonstrated. Overall, the ARA method provides a significant improvement over existing ones in correctly identifying large scale protein-protein interactions,irrespective of the data resource, network size or organism. The MATLAB code for ARA approach will be made available upon request.


Ultrasensitive and fast fluorescent bioassay based on fluorescence enhancement of silver nanoparticles.
An ultrasensitive, fast and specific fluorescent platform for protein detection is developed. In this protocol, silver nanoparticles were conjugated with paramagnetic particles (MPs-Ag) for target capture, concentration and separation; fluorescent dyes functionalized silver nanoparticles (Tag) for generating signals. The presented method is highly sensitive and specific with a detection limit of 2.2 pM for thrombin, and no significant interference was observed for other proteins such as human serum albumin (HSA), lysozyme and IgG. This novel approach combining the magnetic separation and concentration of MPs-Ag, aptamer recognition and fluorescence enhancement of Tag, can be successfully used to enhance the sensitivity of detecting ultra-low levels of target proteins or biomolecules.


Measurement of the Protonic and Electronic Conductivities of PEM Water Electrolyzer Electrodes.
Reducing anode catalyst layer proton- and electron-transport resistances in polymer electrolyte membrane water electrolyzers is critical to improving its performance and maximizing catalyst utilization at high current density. A hydrogen pump technique is adapted to measure the protonic conductivity of IrOx-based catalyst layers. The protonic resistance of the catalyst layer is obtained by subtracting the protonic resistance of an assembly of two NRE211 membranes hot-pressed together from an assembly of two NRE211 membranes with an IrOx intermediate layer. The through-plane and in-plane electronic conductivities were also measured using two- and four-probe methods, respectively. Using these techniques, the protonic and electronic conductivities of the IrOx catalyst layers with varying Nafion loading were measured. The results show that the limiting charge-transport phenomena in the IrOx catalyst layer can be either proton or electron transport, depending on the ionomer loading in the catalyst layer. These results are validated by numerical simulation, as well as by comparison to the high-frequency resistance of an electrolyzer with the same layer.


Human neurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular beta-amyloid or A4 peptides.
The beta-amyloid or beta/A4 peptides that accumulate as filamentous aggregates in the extracellular space of Alzheimer disease (AD) brains are derived from one or more alternatively spliced amyloid precursor proteins (APPs). The more abundant APPs in the central nervous system are the 695-(APP695), 751- (APP751), and 770- (APP770) amino acid isoforms, and each could be the source of beta/A4 peptide that accumulates in the AD brain. It is plausible that altered metabolism of these APPs by central nervous system neurons could lead to the release and deposition of beta/A4 peptide in brain parenchyma. Thus, we examined the expression and processing of the three major brain APPs in nearly pure human neurons (NT2N cells) derived from a teratocarcinoma cell line (NTera2/c1.D1 or NT2 cells) after retinoic acid treatment. NT2N neurons expressed almost exclusively APP695, whereas NT2 cells expressed predominantly APP751/770. Furthermore, the processing of the APPs in NT2N cells was distinct from NT2 and nonneuronal cells. Most significantly, the NT2N neurons but not the NT2 cells constitutively generated intracellular beta/A4 peptide and released it into the culture medium. This work demonstrates the intracellular production of beta/A4 peptide and suggests that cultured NT2N cells may provide a unique model system for understanding the contribution of neurons and APP695 to amyloidogenesis in the AD brain.