Reducing postpartum hemorrhage in Vietnam: assessing the effectiveness of active management of third-stage labor.
The study was undertaken to meet the need of the Ministry of Health to have local evidence on the effectiveness of active management of third-stage labor (AMTSL) in reducing the incidence of postpartum hemorrhage (PPH) > or = 500 mL and the need for PPH treatment. Using a quasi-experimental design, AMTSL was introduced for all births attended by government midwives (at home, community, and district levels) in one district while standard practice without AMTSL was continued in three neighboring districts (with a 1:2 ratio of participants). Oxytocin (10 IU) was administered either by standard disposable syringe and needle or by a prefilled, single-use injection device. Postpartum blood loss was estimated using standard containers; other outcome measures included the duration of third stage, the need for additional treatments, and final maternal condition. A total of 3607 women participated (1236 in the intervention district and 2371 in the comparison districts). Multivariate logistic regression was used to control for age, parity, place of delivery, and first-stage oxytocin augmentation. AMTSL was associated with reduced risks for prolonged third stage beyond 30 min (odds ratio [OR] = 0.20, 95%; confidence interval [CI]: 0.11, 0.35), supplemental oxytocin (OR = 0.68, 95% CI: 0.49, 0.94), and bimanual compression (OR = 0.63, 95%; CI: 0.41, 0.98). When cases with first-stage oxytocin augmentation were excluded, AMTSL was associated with a 34% reduction in PPH incidence (OR = 0.66, 95%; CI: 0.45, 0.98). This study supports the value of AMTSL in reducing the incidence of PPH, shortening the third stage of labor, and reducing the need for additional treatments.


A repurposing strategy identifies novel synergistic inhibitors of Plasmodium falciparum heat shock protein 90.
Malaria is responsible for 3 million deaths annually. Antimalarial drug resistance is widespread, and few novel, well-defined targets exist. A robotic high throughput screen (HTS) was performed using 4000 small molecules from a natural compound (Spectrum), pharmacologically active (Lopac), and Food and Drug Administration (FDA) approved drug library (Prestwick) for competitive inhibition of the ATP-binding (GHKL) domain of Plasmodium falciparum (Pf) Hsp90, a highly conserved chaperone. Hits were further screened for specificity based on differential inhibition of PfHsp90 in comparison to human (Hs) Hsp90. PfHsp90-specific inhibitors showed 50% inhibitory concentrations (IC(50)) in the nanomolar range when tested using a cell-based antimalarial validation assay. Three hits, identified as selective PfHsp90 inhibitors in the HTS, also demonstrated synergistic activity in the presence of the known antimalarial drug chloroquine. These data support PfHsp90 as a specific antimalarial target with potential for synergy with known antimalarials.


A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells.
An Fcalpha receptor probe of human origin was used to identify novel members of the Ig gene superfamily in mice. Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDNAs isolated from a mouse splenic library. Both type I transmembrane proteins possess similar ectodomains with six Ig-like loops, but have different transmembrane and cytoplasmic regions. The predicted PIR-A protein has a short cytoplasmic tail and a charged Arg residue in the transmembrane region that, by analogy with the FcalphaR relative, suggests the potential for association with an additional transmembrane protein to form a signal transducing unit. In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs. These features are shared by the related killer inhibitory receptors. PIR-A proteins appear to be highly variable, in that predicted peptide sequences differ for seven randomly selected PIR-A clones, whereas PIR-B cDNA clones are invariant. Southern blot analysis with PIR-B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A genes. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid lineage cells, wherein both are expressed simultaneously. The characteristics of the highly-conserved PIR-A and PIR-B genes and their coordinate cellular expression suggest a potential regulatory role in humoral, inflammatory, and allergic responses.


Abemaciclib (CDK4/6 Inhibitor) Blockade Induces Cytotoxicity in Human Anaplastic Thyroid Carcinoma Cells.
Thyroid cancer is the most prevalent endocrine malignancies globally. Anaplastic thyroid carcinoma (ATC) accounts for 1-3% of all Thyroid cancer. The evidence showed that ATC is a highly invasive solid tumor with poor prognosis. Despite conventional chemotherapy treatments, a considerable number of patients show developing resistance to therapeutic agents and tumor relapse. The aim of this study was the investigation anti-tumor effect of Abemaciclib (novel targeted cancer therapy drug) on Anaplastic Thyroid carcinoma SW1736 and C643 cell lines. SW1736 and C643 cell lines were treated by desire concentrations of Abemaciclib (0, 1, 2.5, 5, 10, and 20 μM) and cell viability was measured by MTT assay. Also, Anoikis resistance assay was conducted for non-adherent the cells in the exposure of Abemaciclib. The gene expression of apoptotic and anti-apoptotic genes was conducted by quantitative Real-time PCR. Abemaciclib at the concentration of 10 and 20 μM effectively reduced cell proliferation and growth of the ATC cells compared to the control (p=0.000). Furthermore, we showed that 10 and 20 μM doses of the Abemaciclib inhibited the non-adherent ATC cells which were resistant to Anoikis death significantly (p=0.001). Moreover, we demonstrated this targeted therapy significantly reduced anti-apoptotic gene expression levels (BCL2 and CMYC) (p<0.05) and increased apoptotic gene expressions such as P21 and BAX (p<0.05). Our data suggested that Abemaciclib can be utilized as a novel therapeutic agent in ATC cancer. Further in vivo and in vitro investigations are needed to evaluate molecular and clinical mechanisms of Abemaciclib.


Higher Maximal Occlusal Bite Force in Endodontically Treated Teeth Versus Vital Contralateral Counterparts.
Decreased sensitivity to occlusal load could lead to a greater risk of damage to endodontically treated teeth. Therefore, this study aims to test whether root canal treatment reduces the sensitivity of the treated teeth to occlusal load. This is a comparative cross-sectional study of 124 patients who received root canal treatment. Treated teeth were compared with vital teeth on the contralateral side. After interviews with participants, their maximal bite forces (MBFs) of their root canal-treated and contralateral untreated teeth were measured using a digital bite fork force transducer. Data were analyzed by comparing the mean MBF of root canal-treated and control teeth. The mean MBF (± standard deviation) was 226.6 N (±168.7) for root canal-treated teeth and 207.93 N (±158.08) for control teeth. Root canal-treated teeth had a significantly higher difference in the mean MBF than the control group (P < .0001) using the paired sample t test. A univariate analysis test showed that differences in the MBF were affected by molar relationship, overbite, and the quality of root filling. The difference in the MBF was significantly higher in root canal-treated teeth, which is consistent with the function of dental pulp as a highly sensitive sensor. Therefore, the reduction in the sensitivity of teeth to an applied load after pulp removal may increase the risk of overloading. This may, in turn, increase the frequency of tooth damage after root canal treatment.


Syndromes of acquired dyslexia and patterns of recovery: a 6- to 10-year follow-up study of seven brain-injured people.
Seven subjects who were neurologically impaired following encephalitis (n = 2), head injury (n = 3), and stroke (n = 2) were referred several years previously because of acquired dyslexia. Two were almost totally alexic, 2 were surface dyslexic, 2 were deep dyslexic and 1 was a letter-by-letter reader. Following a period of rehabilitation, the 2 with alexia became surface dyslexic and letter-by-letter readers; 1 of the deep dyslexics showed some improvements but remained a deep dyslexic; and the letter-by-letter reader learned to read more quickly. At follow-up, 6 to 10 years later, there had been little significant change. The 2 subjects whose alexia resolved into surface dyslexia with letter-by-letter reading had increased their reading ages but remained surface dyslexic and letter-by-letter readers. The subject who had been a letter-by-letter reader was faster at easier and more frequently used words but slower at harder, less frequently used words. Changes in the other 4 subjects were negligible. Implications for rehabilitation are discussed.


Ultrathin (<1 μm) Substrate-Free Flexible Photodetector on Quantum Dot-Nanocellulose Paper.
Conventional approaches to flexible optoelectronic devices typically require depositing the active materials on external substrates. This is mostly due to the weak bonding between individual molecules or nanocrystals in the active materials, which prevents sustaining a freestanding thin film. Herein we demonstrate an ultrathin freestanding ZnO quantum dot (QD) active layer with nanocellulose structuring, and its corresponding device fabrication method to achieve substrate-free flexible optoelectronic devices. The ultrathin ZnO QD-nanocellulose composite is obtained by hydrogel transfer printing and solvent-exchange processes to overcome the water capillary force which is detrimental to achieving freestanding thin films. We achieved an active nanocellulose paper with ~550 nm thickness, and >91% transparency in the visible wavelength range. The film retains the photoconductive and photoluminescent properties of ZnO QDs and is applied towards substrate-free Schottky photodetector applications. The device has an overall thickness of ~670 nm, which is the thinnest freestanding optoelectronic device to date, to the best of our knowledge, and functions as a self-powered visible-blind ultraviolet photodetector. This platform can be readily applied to other nano materials as well as other optoelectronic device applications.


Regulation of forskolin interactions with type I, II, V, and VI adenylyl cyclases by Gs alpha.
Several forms of adenylyl cyclase (types I, II, V, and VI) have been expressed using the recombinant baculovirus expression system in Sf9 cells. The activation of type I adenylyl cyclase by forskolin and Gs alpha was not greater than additive. In contrast, there was synergistic activation of type II, V, and VI adenylyl cyclases by Gs alpha and forskolin. Gs alpha potentiated the effect of forskolin on type II adenylyl cyclase to the greatest extent. Type I and II adenylyl cyclases were photolabeled specifically by an iodinated photoaffinity derivative of forskolin ([125I]-6-AIPP-Fsk). Type I adenylyl cyclase was photolabeled efficiently in the absence of Gs alpha, and the addition of Gs alpha only slightly increased the labeling efficiency. In contrast, type II adenylyl cyclase was not photolabeled efficiently in the absence of Gs alpha, and the addition of Gs alpha greatly enhanced the labeling efficiency. Photolabeling of type V and VI adenylyl cyclases was detected only in the presence of Gs alpha. Neither calcium/calmodulin nor G protein beta gamma subunits modulated the photolabeling of type I or II adenylyl cyclases. Another iodinated derivative of forskolin, [125I]-6-IHPP-fsk, bound to Sf9 cell membranes expressing type I adenylyl cyclase with high affinity in a filtration binding assay, and the specific binding was not enhanced by the addition of Gs alpha. In contrast, specific binding of [125I]-6-IHPP-Fsk to membranes expressing type II adenylyl cyclase was detected only in the presence of Gs alpha.(ABSTRACT TRUNCATED AT 250 WORDS)


Therapeutic comparison of a new budesonide/formoterol pMDI with budesonide pMDI and budesonide/formoterol DPI in asthma.
Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler). This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged > or = 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50-90% predicted normal and were inadequately controlled on inhaled corticosteroids (500-1600 microg/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 microg, budesonide/formoterol DPI 160/4.5 microg or budesonide/formoterol pMDI 160/4.5 microg. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF). In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: -10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated. Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent.


The relation of body fat distribution, as assessed by six girth measurements, to diabetes mellitus in women.
Independently of the amount of adipose tissue, certain patterns of fat distribution increase the risk of non-insulin-dependent diabetes. Although the ratio of waist to hip (WHR) circumferences has been consistently related to diabetes mellitus, it is possible that only two measures do not completely characterize fat topography. The current study, therefore, examines the cross-sectional relation of six girths (waist, hip, neck, bust, wrist, and ankle) to diabetes mellitus in 43,595 women. As compared with non-diabetics, Quetelet index (kg/m2) and all circumferences were elevated among diabetics. Stratified analyses showed that WHR, and waist, neck, and bust girths were consistently related to diabetes independently of the degree of overweight. As estimated from a logistic regression model that simultaneously controlled for age and all anthropometric variables, the prevalence of diabetes mellitus was positively related to Quetelet index, and to the waist, bust, and neck girths, with odds ratios (ORs) ranging from 1.4 to 2.6. However, diabetes was inversely related to hip (OR = 0.61) and ankle (OR = 0.73) girths; p less than 0.005 for each association. Although cross-sectional in nature, these results suggest that an adverse body fat distribution is not limited to the abdominal region, but that a relative preponderance of adipose tissue in various regions of the upper body is associated with diabetes mellitus in women.


Associations between brain abnormalities and common genetic variants for schizophrenia: a narrative review of structural and functional neuroimaging findings.
Schizophrenia is a common psychotic disease worldwide, and several genetic variants have been suggested to influence susceptibility to schizophrenia. However, the exact genetic and neural mechanisms underlying such relationships remain unclear. Neuroimaging endophenotypes have been considered to be desirable for finding genes influencing brain structure and function. Because of its high penetrance of genetic variants and wide applications in clinic practice, neuroimaging could be a great option in schizophrenia study. In this narrative review, we aim to provide a summary of current progress in neuroimaging findings to detect genetic variants that may influence the brain's structure and function, and thus improve understanding of how this interaction affects the onset of schizophrenia. Multiple common genetic variants for schizophrenia including the ZNF804A, DTNBP1, DAOA, AKT1, NTRK3, and ERBB4 genes are reviewed. In summary, the current investigations have reported effects of these genetic variants on both structural and functional brain abnormalities (e.g., altered grey matter volumes, white matter integrity and functional connectivity patterns) in schizophrenia within multiple brain regions, especially the frontal, temporal and hippocampal areas. These findings facilitate our understanding of schizophrenia and helping us with early diagnosis, prognosis prediction and medication. However, a deep insight into this field necessitate further investigations and there are a number of challenges to be settled, such as enlarging the sample size; solving the statistical, methodological, and technological limitations; performing not only cross-sectional but also longitudinal observations; focusing on the effect of copy number variants; figuring out the complexity of epistasis and gene-environment interaction; achieving clinical translations; and depict the effect of a polygenic risk score beyond those of single genetic markers.


Chemical contaminant exposures assessed using silicone wristbands among occupants in office buildings in the USA, UK, China, and India.
Little is known about chemical contaminant exposures of office workers in buildings globally. Complex mixtures of harmful chemicals accumulate indoors from building materials, building maintenance, personal products, and outdoor pollution. We evaluated exposures to 99 chemicals in urban office buildings in the USA, UK, China, and India using silicone wristbands worn by 251 participants while they were at work. Here, we report concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and other brominated flame retardants (BFRs), organophosphate esters (OPEs), phthalates and phthalate alternatives, pesticides, and polycyclic aromatic hydrocarbons (PAHs). First, we found major differences in office worker chemical exposures by country, some of which can be explained by regulations and use patterns. For example, exposures to several pesticides were substantially higher in India where there were fewer restrictions and unique malaria challenges, and exposures to flame retardants tended to be higher in the USA and UK where there were historic, stringent furniture flammability standards. Higher exposures to PAHs in China and India could be due to high levels of outdoor air pollution that penetrates indoors. Second, some office workers were still exposed to legacy PCBs, PBDEs, and pesticides, even decades after bans or phase-outs. Third, we identified exposure to a contemporary PCB that is not covered under legacy PCB bans due to its presence as an unintentional byproduct in materials. Fourth, exposures to novel BFRs, OPEs, and other chemicals commonly used as substitutes to previously phased-out chemicals were ubiquitous. Fifth, some exposures were influenced by individual factors, not just countries and buildings. Phthalate exposures, for example, were related to personal care product use, country restrictions, and building materials. Overall, we found substantial country differences in chemical exposures and continued exposures to legacy phased-out chemicals and their substitutes in buildings. These findings warrant further research on the role of chemicals in office buildings on worker health.


Novel observations of "freeze resistance" and dynamic blue and green dorsal coloration in frozen and thawing Dryophytes chrysoscelis.
Freeze tolerant animals survive the winter by tolerating the freezing and thawing of up to 70% of body water and the respective cessation and resumption of essential functions including circulation and respiration during each freeze-thaw cycle. Cope's gray treefrog Dryophytes chrysoscelis is a freeze tolerant anuran that uses a system of cryoprotectants to prevent intracellular freezing and mitigate osmotic stress during freezing and thawing episodes. Morphological features were documented in D. chrysoscelis using a repeated freeze-thaw protocol. Dorsal skin in frozen frogs was distinctly blue and green before reverting to brown during thawing. The dorsal color change in frozen frogs does not function similarly to other known color change events in amphibians. The return to brown skin color in thawing animals coincides with recovery of vital functions in freeze tolerant frogs, suggesting that dorsal color change is an indicator of postfreeze recovery in D. chrysoscelis. We also provide evidence of "freeze resistance" in D. chrysoscelis. Two individuals did not freeze following three successive bouts of ice inoculation at -2.5°C and maintained brown dorsal color despite ice crystallization on the dorsum and contact with frozen substrate. Both frogs had similar plasma osmolality, circulating cryoprotectants, and incidence of cryoinjury compared to frogs that were frozen and thawed once or three times. Freeze resistance may be explained by physical changes in the skin including lipid accumulation and dehydration. This integrative study presents novel attributes of organismal freeze tolerance in D. chrysoscelis.


Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease.
Erythropoiesis-stimulating agents used to treat anaemia in patients with chronic kidney disease (CKD) have been associated with cardiovascular adverse events. Hepcidin production, controlled by bone morphogenic protein 6 (BMP6), regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anaemia in CKD patients. To investigate alternative therapies to erythropoiesis-stimulating agents for CKD patients, monoclonal antibodies, LY3113593 and LY2928057, targeting BMP6 and ferroportin respectively, were tested in CKD patients. Preclinical in vitro/vivo data and clinical data in healthy subjects and CKD patients were used to illustrate the translation of pharmacological properties of LY3113593 and LY2928057, highlighting the novelty of targeting these nodes within the hepcidin-ferroportin pathway. LY2928057 bound ferroportin and blocked interactions with hepcidin, allowing iron efflux, leading to increased serum iron and transferrin saturation levels and increased hepcidin in monkeys and humans. In CKD patients, LY2928057 led to slower haemoglobin decline and reduction in ferritin (compared to placebo). Serum iron increase was (mean [90% confidence interval]) 1.98 [1.46-2.68] and 1.36 [1.22-1.51] fold-relative to baseline following LY2928057 600 mg and LY311593 150 mg respectively in CKD patients. LY3113593 specifically blocked BMP6 binding to its receptor and produced increases in iron and transferrin saturation and decreases in hepcidin preclinically and clinically. In CKD patients, LY3113593 produced an increase in haemoglobin and reduction in ferritin (compared to placebo). LY3113593 and LY2928057 pharmacological effects (serum iron and ferritin) were translated from preclinical-to-clinical development. Such interventions may lead to new CKD anaemia treatments.


The impact of the length of total and intravenous systemic antibiotic therapy for the remission of diabetic foot infections.
We investigated the impact of the total length of systemic antibiotic therapy (ABT) and its initial intravenous (IV) part on clinical failure (CF) and microbiological failure (MF) in diabetic foot infections (DFIs). In this single-center, retrospective, unmatched case-control study, we included DFI episodes treated with a combined surgical-antibiotic approach. We included 721 DFI episodes, 537 with osteomyelitis (DFO). CF occurred in 191 (26.5%) and MF in 42 (5.8%) episodes. Multivariate Cox regression analysis showed that a short ABT of 8-21 days (hazard ratio [HR] 0.4; 95% CI 0.2-0.7) was inversely associated with CF. This was also applicable for IV ABT with relatively short durations of 2-7 days (HR 0.5; 95% CI 0.3-0.8) or 8-14 days (HR 0.6; 95% CI 0.4-0.9). We failed to detect a minimal threshold of total or IV ABT predictive for CF or MF. Compared with total ABT of more than 84 days and IV therapy of more than 14 days, shorter total and IV ABT yielded no enhanced risk of CF or MF. Considering the "bias by indication" that is inherent to retrospective DFI studies, the best study design concerning the duration of ABT would be a stratified, prospective randomized trial, which is currently under way in our medical center.


Multiplexed protein quantification with barcoded hydrogel microparticles.
We demonstrate the use of graphically encoded hydrogel microparticles for the sensitive and high-throughput multiplexed detection of clinically relevant protein panels in complex media. Combining established antibody capture techniques with advances in both microfluidic synthesis and analysis, we detected 1-8 pg/mL amounts of three cytokines (interleuken-2, interleuken-4, and tumor necrosis factor alpha) in single and multiplexed assays without the need for filtration or blocking agents. A range of hydrogel porosities was investigated to ensure rapid diffusion of targets and reagents into the particle as well as to maintain the structural integrity of particles during rinsing procedures and high-velocity microfluidic scanning. Covalent incorporation of capture antibodies using a heterobifunctional poly(ethylene glycol) linker enabled one-step synthesis and functionalization of particles using only small amounts of valuable reagents. In addition to the use of three separate types of single-probe particles, the flexibility of the stop-flow lithography (SFL) method was leveraged to spatially segregate the three probes for the aforementioned target set on an individual encoded particle, thereby demonstrating the feasibility of single-particle diagnostic panels. This study establishes the gel-particle platform as a versatile tool for the efficient quantification of protein targets and significantly advances efforts to extend the advantages of both hydrogel substrates and particle-based arrays to the field of clinical proteomics.


Selective modulation of monocyte and neutrophil responses with activated protein C in preterm infants.
Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects. We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation ex vivo in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls. Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry. LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants. Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.


An ordering phase transition, short hydrogen bonds and high Z' in the structure of Ni(Hpydc)2·3H2O.
The structure of Ni(Hpydc)2·3H2O (H2pydc = pyridine-2,6-dicarboxylic acid, also known as dipicolinic acid) has been reinvestigated at variable temperatures. At room temperature, it matches the known structure in the space group P21/c, but at 180 K it undergoes a phase transformation to a twinned structure in Cc. By 120 K, the structure is ordered and twinned with Z' = 4, and shows interesting short hydrogen-bonding interactions that include the formation of hydroxonium species.


Noninvasive evaluation of somatic embryogenesis.
Callus Suspension Cultures of Ipomea batates Poir. cv. White Star were grown in an airlift bioreactor. A machine vision system was used to monitor nondestructively callus growth during a 10 day culture period. Growth data obtained with this system included the overall reactor population and population estimates for the 200-1200-microm fractions at 200-microm intervals. A model of callus growth was developed to explain the mechanics of callus enlargement. The model was based on the assumptions that (1) the calli could not subdivide or shrink, (2) there was a fixed percentage of the initial population for each fraction that was nonviable, and (3) growth rates did not vary with time during the culture period. It was determined that the growth rates and nonviable ratios decreased as fraction size increased.


Overview of reviews in child health: evidence synthesis and the knowledge base for a specific population.
Overviews of reviews are an evolving form of evidence synthesis. The Cochrane Child Health Field has been producing overviews since 2006, during which time the methods that have been used have changed, both due to the development of guidance within The Cochrane Collaboration and to the decisions made by individual author teams. This paper studies the first 29 overviews published in EBCH. To describe some aspects of the approaches taken in EBCH overviews to producing evidence syntheses relevant to the healthcare needs of children; to highlight the contribution that overviews can make to the knowledge base for treatment for a particular population. Data was extracted on: whether the overview included systematic review (SR) data only, or also data from individual trials not present in the included SRs; name(s) of the Cochrane Review Group (CRG) that prepared the included SRs; topics of the overviews as compared to the topics of the included reviews; age-subgroup analyses presented in the overviews. In 23 overviews, all published in 2012, the authors included trial data as well as SR data; two overviews addressed conditions not explicitly addressed by the included reviews; three overviews included pre-specified age-subgroup analyses. The aim of clinical relevance has been achieved by means such as: drawing from reviews produced by multiple CRGs; using SR evidence to explore clinically relevant topics that may not match exactly with the topics covered by the SRs; ensuring that the evidence in overviews is as up to date as possible by redoing searches and including trials not incorporated in the included SRs; and, where permitted by the data, using age-subgroup analyses to present the data in a way which matches the stages of childhood development. Overview authors are dependent on the nature of the data and methods reported in the included SRs. This suggests a need for further study about how SRs could be conducted in order to facilitate the conduct of overviews.


Release of subretinal fluid with the aid of the microscope. Report on 100 cases.
When the incision of the choroid is performed with the aid of the microscope, release of subretinal fluid becomes an absolutely controlled microsurgical procedure. In a consecutive series of 100 eyes, operated with perforation and buckling, an anatomic reattachment rate of 83% was obtained. There have been 4 complications directly related to the release of subretinal fluid, 2 of which healed with good anatomical and functional result after additional treatment.


Co-occurrence of Psychopathology Problems in At-Risk Adolescents.
No known studies have investigated co-occurrence of psychopathology problems in adolescents with biologic and/or environmental susceptibility, including prenatal drug exposure. This study identified comorbidity patterns of psychopathology problems by utilizing data from urban, primarily African American, youth, majority of whom were at heightened risk for exposure to drugs in utero. The roles of Research Domain Criteria (RDoC)-informed behavioral constructs of the Negative Valence (irritability) and Social Process Systems (social disinhibition) as antecedents of the comorbidity patterns were further examined. Lastly, the predictive validity of the identified patterns was evaluated in relation to emerging adulthood outcomes. Participants were 358 urban adolescents, primarily African Americans, drawn from a 21-year prospective birth-cohort study of the effects of prenatal drug exposure. Psychopathology problems were assessed at age 15. Irritability and social disinhibition were self-reported at age 12. Emerging adulthood outcomes were measured at age 21. Latent class modeling indicated four patterns: Normative (57%), substance-use (SU; 24%), mental-health-problems-without-substance-use (MH; 11%), and substance-use-and-other-mental-health-problems (SUMH; 7%). Higher irritability increased the odds of developing the MH pattern, whereas higher social disinhibition increased the odds of developing the SU pattern. The odds of manifesting the SUMH pattern were higher for children with higher irritability. For children with higher social disinhibition, the odds of manifesting the SUMH pattern were higher at a trend level. Adolescent comorbidity patterns were differentially associated with problematic tobacco and marijuana use and clinically relevant mental health problems in emerging adulthood, and completion of high school education. Peri-pubertal identification of individual differences in irritability and social disinhibition may mitigate the emergence of adolescent psychopathology, which could influence emerging adulthood adjustment in this at-risk population.


Preparation of a nano- and micro-fibrous decellularized scaffold seeded with autologous mesenchymal stem cells for inguinal hernia repair.
Prosthetic meshes used for hernioplasty are usually complicated with chronic pain due to avascular fibrotic scar or mesh shrinkage. In this study, we developed a tissue-engineered mesh (TEM) by seeding autologous bone marrow-derived mesenchymal stem cells onto nanosized fibers decellularized aorta (DA). DA was achieved by decellularizing the aorta sample sequentially with physical, mechanical, biological enzymatic digestion, and chemical detergent processes. The tertiary structure of DA was constituted with micro-, submicro-, and nanosized fibers, and the original strength of fresh aorta was retained. Inguinal hernia rabbit models were treated with TEMs or acellular meshes (AMs). After implantation, TEM-treated rabbit models showed no hernia recurrence, whereas AM-treated animals displayed bulges in inguinal area. At harvest, TEMs were thicker, have less adhesion, and have stronger mechanical strength compared to AMs (P<0.05). Moreover, TEM showed better cell infiltration, tissue regeneration, and neovascularization (P<0.05). Therefore, these cell-seeded DAs with nanosized fibers have potential for use in inguinal hernioplasty.


High impact of uranyl ions on carrying-releasing oxygen capability of hemoglobin-based blood substitutes.
The effect of radioactive UO2 (2+) on the oxygen-transporting capability of hemoglobin-based oxygen carriers has been investigated in vitro. The hemoglobin (Hb) microspheres fabricated by the porous template covalent layer-by-layer (LbL) assembly were utilized as artificial oxygen carriers and blood substitutes. Magnetic nanoparticles of iron oxide (Fe3 O4 ) were loaded in porous CaCO3 particles for magnetically assisted chemical separation (MACS). Through the adsorption spectrum of magnetic Hb microspheres after adsorbing UO2 (2+) , it was found that UO2 (2+) was highly loaded in the magnetic Hb microspheres, and it shows that the presence of UO2 (2+) in vivo destroys the structure and oxygen-transporting capability of Hb microspheres. In view of the high adsorption capacity of UO2 (2+) , the as-assembled magnetic Hb microspheres can be considered as a novel, highly effective adsorbent for removing metal toxins from radiation-contaminated bodies, or from nuclear-power reactor effluent before discharge into the environment.


Antigenic variation of influenza A virus nucleoprotein detected with monoclonal antibodies.
Monoclonal antibodies were used to study antigenic variation in the nucleoprotein of influenza A viruses. We found that the nucleoprotein molecule of the WSN/33 strain possesses at least five different determinants. Viruses of other influenza A virus subtypes showed antigenic variation in these nucleoprotein determinants, although changes in only one determinant were detected in H0N1 and animal strains. The nucleoprotein of human strains isolated from 1933 through 1979 could be divided into six groups, based on their reactivities with monoclonal antibodies; these groups did not correlate with any particular hemagglutinin or neuraminidase subtype. Our results indicate that antigenic variation in the nucleoproteins of influenza A viruses proceeds independently of changes in the viral surface antigens and suggest that point mutations and genetic reassortment may account for nucleoprotein variability.


Adsorption Capability of Cationic Dyes (Methylene Blue and Crystal Violet) onto Poly-γ-glutamic Acid.
In this study, the adsorption capability of cationic dyes, which were methylene blue and crystal violet, by poly-γ-glutamic acid (PGA) in a single or binary solution system was investigated. The effect of the molecular weight of PGA, initial dye concentration, solution pH, and temperature on the adsorption of dyes was evaluated. The adsorption mechanism of dyes onto PGA was the interaction between -COOH group on the PGA surface and the polarity groups of dyes. These results indicated that PGA is useful for removal of dyes and cationic organic compounds from a single or binary solution system.


Identification of novel hereditary cancer genes by whole exome sequencing.
Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with ovarian hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years.


A one-dimensional coordination polymer formed from the reaction of 1,1-diphenyl-3,3'-[(1R,2R)-cyclohexane-1,2-diylbis(azanediyl)]dibut-2-en-1-one with MnCl2·4H2O.
In the title coordination polymer, catena-poly[[dichloridomanganese(II)]-μ-1,1-diphenyl-3,3'-[(1R,2R)-cyclohexane-1,2-diylbis(azaniumylylidene)]dibut-1-en-1-olate-κ(2)O:O'], [MnCl2(C26H30N2)]n, synthesized by the reaction of the chiral Schiff base ligand 1,1-diphenyl-3,3'-[(1R,2R)-cyclohexane-1,2-diylbis(azanediyl)]dibut-2-en-1-one (L) with MnCl2·4H2O, the asymmetric unit contains one crystallographically unique Mn(II) ion, one unique spacer ligand, L, and two chloride ions. Each Mn(II) ion is four-coordinated in a distorted tetrahedral coordination environment by two O atoms from two L ligands and by two chloride ligands. The Mn(II) ions are bridged by L ligands to form a one-dimensional chain structure along the a axis. The chloride ligands are monodentate (terminal). The ligand is in the zwitterionic enol form and displays intramolecular ionic N(+)-H...O(-) hydrogen bonding and π-π interactions between pairs of phenyl rings which strengthen the chains.


miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS.
A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice. Integrated transcriptome profiling and biotin-affinity miRNA pull-down approaches reveal stage-specific miR-219 targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune encephalomyelitis, principal animal models of multiple sclerosis. Together, our findings identify context-specific miRNA-regulated checkpoints that control myelinogenesis and a therapeutic role for miR-219 in CNS myelin repair.


Long-Term Performance of a Pilot-Scale Gas-Sparged Anaerobic Membrane Bioreactor under Ambient Temperatures for Holistic Wastewater Treatment.
Concerns regarding ambient temperature operation, dissolved methane recovery, and nutrient removal have limited the implementation of anaerobic membrane bioreactors (AnMBRs) for domestic wastewater treatment. This study addresses these challenges using a pilot-scale gas-sparged AnMBR, with post-treatment recovery of dissolved methane and nutrients. Operating under ambient temperatures for 472 days, the AnMBR achieved an average effluent quality of 58 ± 27 mg/L COD and 25 ± 12 mg/L BOD5 at temperatures ranging from 12.7 to 31.5 °C. The average total methane yield was 0.14 ± 0.06 L-CH4/g-COD fed, with 42% of the total methane dissolved in the permeate. Dissolved methane removal using a hollow fiber membrane contactor achieved an average removal efficiency of 70 ± 5%, producing effluent dissolved methane concentrations of 3.8 ± 0.94 mg/L. The methane recovered from gaseous and dissolved fractions could generate an estimated 72.8% of the power required for energy neutrality. Nutrient recovery was accomplished using coagulation, flocculation, and sedimentation for removal of sulfide and phosphorus, followed by a clinoptilolite ion-exchange column for removal of ammonia, producing effluent concentrations of 0.7 ± 1.7 mg-S/L, 0.43 ± 0.29 mg-P/L and 0.05 ± 0.05 mg-N/L. The successful integration of AnMBRs in a treatment train that addresses the critical challenges of dissolved methane and nutrients demonstrates the viability of the technology in achieving holistic wastewater treatment.


RNAi-directed assembly of heterochromatin in fission yeast.
Heterochromatin is an epigenetically heritable and conserved feature of eukaryotic chromosomes with important roles in chromosome segregation, genome stability, and gene regulation. The formation of heterochromatin involves an ordered array of chromatin changes, including histone deacetylation, histone H3-lysine 9 methylation, and recruitment of histone binding proteins such as Swi6/HP1. Recent discoveries have uncovered a role for the RNA interference (RNAi) pathway in heterochromatin assembly in the fission yeast Schizosaccharomyces pombe and other eukaryotes. Purification of two RNAi complexes, RITS and RDRC, from fission yeast has provided further insight into the mechanism of RNAi-mediated heterochromatin assembly. These discoveries have given rise to a model in which small interfering RNA molecules act as specificity factors that initiate epigenetic chromatin modifications and double strand RNA synthesis at specific chromosome regions.


High-throughput screening of suppression subtractive hybridization cDNA libraries using DNA microarray analysis.
Efficient construction of cDNA libraries enriched for differentially expressed transcripts is an important first step in many biological investigations. We present a quantitative procedure for screening cDNA libraries constructed by suppression subtractive hybridization (SSH). The methodology was applied to two independent SSHs from pearl millet and banana. Following two-color cyanin dye labeling and hybridization of subtracted tester with either unsubtracted driver or unsubtracted tester cDNAs to the SSH libraries arrayed on glass slides, two values were calculated for each clone, an enrichment ratio 1 (ER1) and an enrichment ratio 2 (ER2). Graphical representation of ER1 and ER2 enabled the identification of clones that were likely to represent up-regulated transcripts. Normalization of each clone by the SSH process was determined from the ER2 values, thereby indicating whether clones represented rare or abundant transcripts. Differential expression of pearl millet and banana clones identified from both libraries by this quantitative approach was verified by inverse Northern blot analysis.


Truncated apolipoprotein C-I induces apoptosis in neuroblastoma by activating caspases in the extrinsic and intrinsic pathways.
Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control. The results of the CCK-8 assay showed that the truncated peptide selectively inhibited cell proliferation compared with the signal peptide, and inhibited migration and invasion as determined by wound healing and Transwell assays. Flow cytometry analysis demonstrated that the truncated peptide induced apoptosis and cell cycle arrest in the S phase. Bax, Bim, and tBid upregulation, and Bcl‑2 and Bcl‑xl downregulation were associated with permeabilization of the mitochondrial membrane, as detected by the JC-1 assay and the release of cytochrome c and apoptosis. Activation of caspase‑8 was associated with activation of cell death receptors such as the tumor necrosis factor receptor. PARP cleavage indicated apoptosis, and DNA damage was observed in the TUNEL assay. The results showed that the truncated apoC-I induced apoptosis in neuroblastoma by the extrinsic and intrinsic pathways. The anticancer effects were confirmed in vivo in a xenograft mouse model. In conclusion, the endogenous protein apoC-I may be a new promising therapeutic target to suppress tumor growth.


ATF3 and JDP2 deficiency in cancer associated fibroblasts promotes tumor growth via SDF-1 transcription.
The activating transcription factor 3 (ATF3) and the c-Jun dimerization protein 2 (JDP2) are members of the basic leucine zipper (bZIP) family of transcription factors. These proteins share a high degree of homology and both can activate or repress transcription. Deficiency of either one of them in the non-cancer host cells was shown to reduce metastases. As ATF3 and JDP2 compensate each other's function, we studied the double deficiency of ATF3 and JDP2 in the stromal tumor microenvironment. Here, we show that mice with ATF3 and JDP2 double deficiency (designated thereafter dKO) developed larger tumors with high vascular perfusion and increased cell proliferation rate compared to wild type (WT) mice. We further identify that the underlying mechanism involves tumor associated fibroblasts which secrete high levels of stromal cell-derived factor 1 (SDF-1) in dKO fibroblasts. SDF-1 depletion in dKO fibroblasts dampened tumor growth and blood vessel perfusion. Furthermore, ATF3 and JDP2 were found to regulate SDF-1 transcription and secretion in fibroblasts, a phenomenon that is potentiated in the presence of cancer cells. Collectively, our results suggest that ATF3 and JDP2 regulate the expression of essential tumor promoting factors expressed by fibroblasts within the tumor microenvironment, and thus restrain tumor growth.


Spectrum of histological lesions in 185 consecutive prostatic specimens.
One hundred and eighty five consecutive prostate specimens were studied. The predominant lesion noted was benign prostatic hyperplasia (B.P.H.) (92.97%). The incidence of carcinoma was low, (7.02%). Conditions which can mimic and should be considered in the differential diagnosis of carcinoma, like basal cell hyperplasia, atypical hyperplasia and atrophy associated hyperplasia were noted in 10, 4 and 3 cases of B.P.H. respectively. None of these cases showed evidence of carcinoma. Corpora amylacea were noted in 38.91% of the cases of B.P.H. and were conspicuously absent in cases of carcinoma. Chronic prostatitis was frequently encountered (58%) and metaplastic changes were seen in 11% of the cases.


A Twelve-Year Consecutive Case Experience in Thoracic Reconstruction.
We describe the second largest contemporary series of flaps used in thoracic reconstruction. A retrospective review of patients undergoing thoracomyoplasty from 2001 to 2013 was conducted. Ninety-one consecutive patients were identified. Thoracomyoplasty was performed for 67 patients with intrathoracic indications and 24 patients with chest wall defects. Malignancy and infection were the most common indications for reconstruction (P < 0.01). The latissimus dorsi (LD), pectoralis major, and serratus anterior muscle flaps remained the workhorses of reconstruction (LD and pectoralis major: 64% flaps in chest wall reconstruction; LD and serratus anterior: 85% of flaps in intrathoracic indication). Only 12% of patients required mesh. Only 6% of patients with <2 ribs resected required mesh when compared with 24% with 3-4 ribs, and 100% with 5 or more ribs resected (P < 0.01). Increased rib resections required in chest wall reconstruction resulted in a longer hospital stay (P < 0.01). Total comorbidities and complications were related to length of stay only in intrathoracic indication (P < 0.01). Average intubation time was significantly higher in patients undergoing intrathoracic indication (5.51 days) than chest wall reconstruction (0.04 days), P < 0.05. Average hospital stay was significantly higher in patients undergoing intrathoracic indication (23 days) than chest wall reconstruction (12 days), P < 0.05. One-year survival was most poor for intrathoracic indication (59%) versus chest wall reconstruction (83%), P = 0.0048. Thoracic reconstruction remains a safe and successful intervention that reliably treats complex and challenging problems, allowing more complex thoracic surgery problems to be salvaged.


Screening Patients With Cataract for Premium IOL Candidacy Using Microperimetry.
To explore the use of microperimetry in the evaluation of macular dysfunction in patients with cataract, to aid in proper intraocular lens selection (multifocal vs monofocal), and to set expectations for postoperative visual function. One randomly chosen eye of 10 patients diagnosed as having mild (1+) to moderate (3+) cataract was evaluated before and 1 week after cataract surgery with the MAIA microperimeter (Centervue S.p.A, Padova, Italy). Corrected distance visual acuity, dilated and undilated biomicroscopy and indirect fundus examinations, intraocular pressure measurement, and a MAIA microperimeter test to measure macular sensitivity and fixation pattern were also performed. Two patients showed macular abnormalities before and after surgery that were noted on MAIA testing: one patient showed reduced average threshold sensitivity and abnormal percent reduced threshold, whereas the other patient showed fixation drift demonstrating eccentric fixation. Both eyes had reduced postoperative visual performance after uneventful cataract surgeries. Because not every macular lesion noted on fundus examination or optical coherence tomography may be clinically significant, microperimetry can be useful to detect clinically significant retinal dysfunction prior to cataract surgery. The outcome may aid in the selection of intraocular lens type and may yield a better documented surgical prognosis. Further studies are necessary to confirm these findings.


Effects of androgen on vascular and inflammatory biomarkers in a female hypertensive population.
Androgen is a steroid hormone associated with high blood pressure (BP). The effect of androgen on BP in females is unknown. Androgen, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 were evaluated in females with menstruation disorders (n = 135, 28 ± 5 years old) and normal BP, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Normal-BP (n = 57), pre-hypertension (n = 44), stage-1-hypertension (n = 21), and stage-2-hypertension (n = 13) females had similar androgen (3.3 ± 1.5, 2.7 ± 1.2, 3.1 ± 1.4, and 3.5 ± 1.3 ng/ml, p > 0.05) and IL-6 levels (1.7 ± 2.2, 1.9 ± 2.6, 1.3 ± 1.2 and 2.4 ± 3.3 pg/ml, p > 0.05). However, normal BP females had lower MMP-9 (609 ± 307 versus 891 ± 385 ng/ml, p < 0.05) than stage-1-hypertension females. In addition, normal BP females had lower VEGF (166 ± 103 versus 255 ± 139, 272 ± 128 and 301 ± 216 pg/ml, p < 0.05) than the other three groups. In normal-androgen females, VEGF levels were similar among the four groups. However, in high-androgen females, normal BP groups had lower VEGF levels than pre-hypertension, stage-1, and stage-2 hypertension groups (166 ± 94 versus 294 ± 153, 281 ± 160 and 357 ± 253 p < 0.05). Androgen can modulate growth factors and extracellular matrix proteins, which may contribute to the pathophysiology of hypertension in young females.


[Surgical management of infectious keratitis].
Infectious keratitis is one of the most common causes of blindness worldwide. Despite the existence of a wide arsenal of quite effective antimicrobial drugs, some forms of bacterial and viral keratitis are resistant. Advanced acanthamoeba and mycotic lesions of the cornea, as well as mixed forms of infection usually do not respond well to conservative treatment. In the absence of positive dynamics from the applied etiotropic therapy with observed further progression of the microbial process, there is a risk of corneal perforation and spread of infection to the sclera or deep ocular structures with a high probability of irreversible functional disorders or anatomical death of the eye. In such cases, a timely transition to surgical treatment is necessary in order to maintain structural integrity of the eyeball. For this purpose, corneal crosslinking, microdiathermocoagulation, tissue adhesive, autoconjunctival plasty, amniotic membrane, corneoscleral flap coating, various combinations of these methods, as well as therapeutic keratoplasty are used most often in clinical practice. The choice depends on the etiology, size and depth of the lesion, its localization, prognosis of visual outcomes, somatic status of the patient. Therapeutic keratoplasty is the most radical and effective method of surgical intervention that allows eradication of the infectious focus and best possible restoration of the structural integrity of the eyeball. However, in some cases due to inaccessibility of donor material or high risks of the surgery and non-transparent graft engraftment, it is advised to use alternative surgical approaches, and keratoplasty, if necessary, should be carried out for optical purposes at a further, "quiet" period.


Interlocking wedge osteotomy of the proximal tibia for gonarthrosis.
Modification of the lateral closing wedge osteotomy of the proximal tibia is described for gonarthrosis associated with varus deformities. In this procedure, the anterior and posterior cortices are left attached to the distal and proximal fragments respectively when the bone wedge is removed. The defect is closed by applying valgus stress and medial rotation to the distal fragment so that the tibial tubercle advances anteriorly and the posterior cortex of the proximal fragment overrides the distal fragment. Contact area and stability at the osteotomy site are increased by an interlocking effect of the cortices and the stress under the patella is reduced by anterior advancement of the tibial tubercle. Satisfactory results have been obtained in 36 cases followed for one to three years with few complications.


Recognition Moieties of Small Molecular Fluorescent Probes for Bioimaging of Enzymes.
Enzymes are a class of important substances for life, and their abnormal levels are associated with many diseases. Thus, great progress has been made in the past decade in detecting and imaging enzymes in living biosystems, and in this respect fluorescent probes combined with confocal microscopy have attracted much attention because of their high sensitivity and unrivaled spatiotemporal resolution. Fluorescent probes are usually composed of three moieties: a signal or fluorophore moiety, a recognition or labeling moiety, and an appropriate linker to connect the two aforementioned moieties. At present, however, research and reviews on enzymatic probes mostly focus on fluorophores and/or linkers, whereas those on the recognition moiety are relatively few. Moreover, current enzymatic probes with some recognition moieties have drawbacks such as poor selectivity, high background fluorescence, or/and low sensitivity and are unsatisfactory for practical applications. Thus, developing new recognition moieties with higher specificity or/and sensitivity to the enzyme of interest is very desirable but still challenging. In this Account, we introduce the recognition moieties of fluorescent probes for several enzymes, including tyrosinase, monoamine oxidase A (MAO-A), nitroreductase (NTR), and aminopeptidases. Highlights are given on how new specific recognition moieties of tyrosinase and MAO-A were designed to eliminate the interference by reactive oxygen species (ROS) and MAO-B, respectively. Here we present four recent examples in which designed fluorescent probes are employed to image enzymes in living biosystems. The first example shows that 3-hydroxyphenyl can serve as a new and more specific recognition moiety than the traditional 4-hydroxyphenyl group for tyrosinase, enabling the development of a highly selective fluorescent probe for imaging of tyrosinase without interference by ROS. The second presents a general design strategy for fluorescent probes specific for an enzyme, which involves combining the characteristic structure of an inhibitor of the target enzyme along with its traditional reactive group as a new recognition moiety, and successfully demonstrates it by selective detection of MAO-A in the presence of its isomeric MAO-B. The third mainly illustrates that 5-nitrothiophen-2-yl alcohol with a stronger electron-donating S atom is a better fluorescence quenching and recognition moiety than 5-nitrofuran-2-yl alcohol for NTR, leading to the development of a highly sensitive method for NTR assay. Lastly, on the basis of known observations, we show that besides the specific interaction with the target, another function of some recognition moieties may be responsible for tuning the fluorescence signal, which is exemplified by the linking of several aminopeptidases' recognition moieties to the free hydroxyl or amino group of different fluorophores. It is our wish that this Account will promote the appearance of more specific recognition moieties and fluorescent probes with excellent properties and that new biofunctions of the enzymes will be uncovered.


Treat-to-target for osteoporosis: is now the time?
Current clinical practice guidelines identify patients at high risk for fracture who are likely to benefit from pharmacological therapy and suggest ways to monitor for effectiveness of therapy. However, there is no clear guidance on when fracture risk has been reduced to an acceptably low level. As a consequence, some patients at low risk for fracture may be treated for longer than necessary, whereas others at high risk for fracture may have treatment stopped when they might benefit from continuation of the same treatment or a change to a more potent therapeutic agent. The objective of this statement is to describe the potential clinical utility of developing a "treat-to-target" strategy for the management of patients with osteoporosis. We recommend that a task force of clinicians, clinical investigators, and other stakeholders in the care of osteoporosis explore the options, review the evidence, and identify additional areas for investigation to establish osteoporosis treatment targets. Data from large, prospective, randomized, placebo-controlled registration trials for currently available osteoporosis therapies should be analyzed for commonalities of correlations between easily measured endpoints and fracture risk. Osteoporosis experts, professional organizations, and patient care advocates should be involved in the process of developing consensus on easily measurable osteoporosis treatment targets that are supported by the best available evidence and likely to be accepted by clinicians and patients in the care of osteoporosis. A treat-to-target strategy for osteoporosis offers the potential of improving osteoporosis care by reducing the burden of osteoporotic fractures and limiting adverse effects of therapy.


The Calvin cycle enzyme phosphoglycerate kinase of Xanthobacter flavus required for autotrophic CO2 fixation is not encoded by the cbb operon.
During autotrophic growth of Xanthobacter flavus, energy derived from the oxidation of hydrogen methanol or formate is used to drive the assimilation of CO2 via the Calvin cycle. The genes encoding the Calvin cycle enzymes are organized in the cbb operon, which is expressed only during autotrophic growth. Although it has been established that the transcriptional activator CbbR is required for the expression of the cbb operon, it is unclear whether CbbR is the only factor contributing to the regulation of the cbb operon. This paper describes the isolation of X. flavus mutants which were affected in the regulation of the cbb operon. One of the mutant strains was subject to an enhanced repression of the cbb operon promoter by the gluconeogenic substrate succinate and in addition failed to grow autotrophically. The rate of growth of the X. flavus mutant on succinate-containing medium was lower than that of the wild-type strain, but rates of growth on medium supplemented with gluconate were identical. A genomic library of X. flavus was constructed and was used to complement the mutant strain. The nucleotide sequence of the DNA fragment required to restore autotrophic growth of the X. flavus mutant was determined. One open reading frame that displayed extensive similarities to phosphoglycerate kinase-encoding genes (pgk) was identified. The X. flavus mutant lacked phosphoglycerate kinase activity following growth on gluconate or succinate. Introduction of the pgk gene into the X. flavus mutant partially restored the activity of phosphoglycerate kinase. Induction of the cbb operon of the X. flavus wild-type strain resulted in a simultaneous and parallel increase in the activities of ribulose-1,5-biphosphate carboxylase and phosphoglycerate kinase, whereas the latter activity remained absent in the X. flavus pgk mutant. It is concluded that X. flavus employees a single phosphoglycerate kinase enzyme and this is not encoded within the cbb operon.


RICD: a rice indica cDNA database resource for rice functional genomics.
The Oryza sativa L. indica subspecies is the most widely cultivated rice. During the last few years, we have collected over 20,000 putative full-length cDNAs and over 40,000 ESTs isolated from various cDNA libraries of two indica varieties Guangluai 4 and Minghui 63. A database of the rice indica cDNAs was therefore built to provide a comprehensive web data source for searching and retrieving the indica cDNA clones. Rice Indica cDNA Database (RICD) is an online MySQL-PHP driven database with a user-friendly web interface. It allows investigators to query the cDNA clones by keyword, genome position, nucleotide or protein sequence, and putative function. It also provides a series of information, including sequences, protein domain annotations, similarity search results, SNPs and InDels information, and hyperlinks to gene annotation in both The Rice Annotation Project Database (RAP-DB) and The TIGR Rice Genome Annotation Resource, expression atlas in RiceGE and variation report in Gramene of each cDNA. The online rice indica cDNA database provides cDNA resource with comprehensive information to researchers for functional analysis of indica subspecies and for comparative genomics. The RICD database is available through our website http://www.ncgr.ac.cn/ricd.


Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations: A PRISMA-compliant meta-analysis.
Recently, a growing number of studies show that the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms may play a role in the systemic lupus erythematosus (SLE) susceptibility. Nonetheless, the results were inconsistent. Thus, a meta-analysis was carried out by integrating multiple research to clarify the association between KIR polymorphisms and SLE susceptibility. The Web of Science, Embase (Ovid), PubMed, Elsevier Science Direct, the Chinese Biomedical Database and CNKI, Wanfang databases (last search was updated on May 15, 2016) were systematically searched to select studies on addressing the association between the KIR polymorphisms and susceptibility to SLE in populations. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated. A total of 10 published case-control studies involving 1450 SLE patients and 1758 controls were available for this meta-analysis. Results suggested that KIR2DL1 might be a risk factor for SLE (OR 2DL1 =1.047, 95% CI=1.011-1.083) in all subjects. The KIR2DL3, KIR2DL5 were identified as protective factors for SLE in Asian populations (OR2DL3= 0.215, 95% CI = 0.077-0.598; OR2DL5 = 0.588, 95% CI = 0.393-0.881), but not in Caucasians. The meta-analysis results suggested that 2DL1 might be a potential risk factor and 2DL3, 2DL5 might be protective factors for SLE in Asians but not in Caucasians.


Phloem-mobile messenger RNAs and root development.
Numerous signal molecules move through the phloem to regulate development, including proteins, secondary metabolites, small RNAs and full-length transcripts. Several full-length mRNAs have been identified that move long distances in a shootward or rootward direction through the plant vasculature to modulate both floral and vegetative processes of growth. Here we discuss two recently discovered examples of long-distance transport of full-length mRNAs into roots and the potential target genes and pathways for these mobile signals. In both cases, the mobile RNAs regulate root growth. Previously, RNA movement assays demonstrated that transcripts of StBEL5, a transcription factor from the three-amino-loop-extension superclass, move through the phloem to stolon tips to enhance tuber formation in potato (Solanum tuberosum L.). StBEL5 mRNA originates in the leaf and its movement to stolons is induced by a short-day photoperiod. Movement of StBEL5 RNA to roots correlated with increased growth and the accumulation of several transcripts associated with hormone metabolism, including GA2-oxidase1, YUCCA1a and -c, several Aux/IAA types, and PIN1, -2, and -4 was observed. In another example, heterografting techniques were used to identify phloem-mobile Aux/IAA transcripts in Arabidopsis. Movement assays confirmed that these Aux/IAA transcripts are transported into the root system where they suppress lateral root formation. Phloem transport of both StBEL5 and Aux/IAA RNAs are linked to hormone metabolism and both target auxin synthesis genes or auxin signaling processes. The mechanisms of transport for these mobile RNAs, the impact they have on controlling root growth, and a potential transcriptional connection between the BEL1/KNOX complex and Aux/IAA genes are discussed.


[3 summit conferences on Earth insufficient to save the Planet, Controversies and achievements].
This review summarizes the present concerns on the deteriorated biological systems. This concern has generated many publications since it is a very serious subject. The human being has produced a deep impact on the environment that could even could induce climatic changes. Because these circumstances have increased the socioeconomical differences between developed and third world countries, the United Nations Organization had organized three summit conferences (Oslo, 1972; Rio do Janeiro, 1992; Johannesburgh, 2002) in order to propose solutions. This review discusses the conclusions held at these conferences.


Assessment of salt intake: how accurate is it?
The aims of this review paper are to provide an overview of the association of sodium intake with cardiovascular health, to identify sodium in our global food supply and to describe problems associated with assessment of dietary sodium intake. Excess sodium intake may contribute to the development of hypertension in some individuals, consequently increasing CVD risk. The average intake of sodium in populations around the world far exceeds the actual body's needs. Processed and restaurant foods contribute the most dietary sodium for Americans and other populations worldwide. There is a worldwide focus on reducing sodium content of food products in an effort to reduce health related issues associated with excessive salt and sodium intake in individuals. In several countries, regulations have been introduced to lower the sodium content of foods. Manufacturers are complying with these regulations by formulating new products to meet these standards. However, the variability in food sodium content poses challenges to researchers to accurately assess dietary sodium intakes of individuals. There are differences in sodium content of foods in databases compared with nutritional information provided by manufacturers for the same food products. Variations also exist in restaurant foods, where values differ from those available on restaurant websites. Sodium may be either underestimated or overestimated; it is not always on target. Awareness of the variability among food products is crucial but capturing sodium content of every food in the market is not feasible. Whenever possible, updating databases is critical. In conclusion, it is not feasible to capture the sodium content of every food in the marketplace but being aware of these differences is essential to assessing actual sodium consumption. Since biological determinations are burdensome and impractical, it is imperative for researchers and other health professionals to participate in the development and implementation of tools to accurately assess sodium intake in individuals.


Midwives and HIV: the case for continuing education.
On a worldwide scale, HIV transmission figures continue to rise dramatically. This paper looks at the impact the pandemic is likely to have on women of childbearing age in the future. The author finds that if current statistical predictions are to become a reality, midwives and perinatal nursing staff are increasingly likely to be exposed to clients with the disease or carrying the virus. Continuing staff education, she says, is crucial.


Estimation of the depth of left-sided double-lumen endobronchial tube placement using preoperative chest radiographs.
Accurate placement of the double-lumen endobronchial tube (DLETs) is essential for optimal gas exchange during one-lung ventilation. The present study was designed to estimate the insertion depth of left-sided DLET using a preoperative chest radiograph. Forty-five patients who underwent thoracic operations requiring intubation of a DLET were studied. The distance between the cephalic edge of the sixth cervical vertebra and the carina of the trachea (Dc-c) was measured from the anterior-posterior view of preoperative chest radiograph. After the tube was positioned in the main bronchus, a fiberoptic bronchoscope was introduced into the tracheal lumen to ensure the appropriate position of the DLET. Simple regression analysis for the insertion depth of the DLETs and Dc-c was performed. There was a highly significant correlation between the insertion depth of the DLET and both the Dc-c (y = 0.5304x + 19.646) and the body height (y = 0.1022x + 10.525), with P < 0.001 and P < 0.01, respectively. To get the distance from the cephalic edge of the 6th cervical vertebra to the Dc-c from the chest radiograph preoperatively would be helpful for the evaluation of the proper insertion depth of the placement of DLET.


Theoretical Investigation of the Reactivity of Sodium Dicyanamide with Nitric Acid.
There is a need to replace current hydrazine fuels with safer propellants, and dicyanamide (DCA-)-based systems have emerged as promising alternatives because they autoignite when mixed with some oxidizers. Previous studies of the hypergolic reaction mechanism have focused on the reaction between DCA- and the oxidizer HNO3; here, we compare the calculated pathway of DCA- + HNO3 with the reaction coordinate of the ion pair sodium dicyanamide with nitric acid, Na[DCA] + HNO3. Enthalpies and free energies are calculated in the gas phase and in solution using a quantum mechanical continuum solvation model, SMD-GIL. The barriers to the Na[DCA] + HNO3 reaction are dramatically lowered relative to those of the reaction with the bare anion, and an exothermic exit channel to produce NaNO3 and the reactive intermediate HDCA appears. These results suggest that Na[DCA] may accelerate the ignition reaction.


Biodegradable protein-based rockets for drug transportation and light-triggered release.
We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.


Agar/collagen membrane as skin dressing for wounds.
Agar, a highly hydrophilic polymer, has a special gel property and favorable biocompatibility, but moderate intension strength in an aqueous condition and a low degradation rate. In order to tailor both properties of mechanical intension and degradation, type I collagen was composited with agar in a certain ratio by drying at 50 degrees C or by a freeze-dry process. Glutaraldehyde was chosen as a crosslinking agent, and the most favorable condition for crosslinking was that the weight ratio of agar to glutaraldehyde was 66.7 and the pH value about 5. Dynamic mechanical analysis results showed that the single agar membrane had a modulus value between 640 MPa and 1064 MPa, but it was between 340 MPa and 819 MPa after being composited with type I collagen. It was discovered under an optical microscope that the pores were interconnected in the composite scaffolds instead of the honeycomb-like pores in a single type I collagen scaffold or the laminated gaps in a single agar scaffold. The results of an acute toxicity test disclosed that the composites were not toxic to mice although the composites were crosslinked with a certain concentration of glutaraldehyde. The results of gross examinations showed that when the composite membranes or scaffolds were applied to a repair rabbit skin lesion, the composites had a good repair effect without infection, liquid exudation or visible scar in the lesion covered with them. But in the control group, the autologous skin showed necrosis and there were a lot of scar tissues in the lesion site. H&E staining results showed that the repair tissue was similar to the normal one and very few scaffolds or membranes were left without degradation after 2 or 3 weeks. In conclusion, it is proved that type I collagen increases the toughness of the agar membrane, and the agar/type I collagen composites are promising biomaterials as wound dressings for healing burns or ulcers.


Effectiveness of monopolar dielectric transmission of pulsed electromagnetic fields for multiple sclerosis-related pain: a pilot study.
Pain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing. This study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale. Statistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups. Treatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment.


A PTP4A3 peptide PIMAP39 modulates TNF-alpha levels and endotoxic shock.
Lipopolysaccharide (LPS) stimulation of macrophages initiates intracellular signaling pathways leading to activation of MAPK and its subsequent influence on cytokine production. We recently identified a LITAF-STAT6(B) complex regulated by p38 MAPK in response to LPS stimulation. However, the LPS-induced cascade in the p38/LITAF/TNF signaling pathway remains unclear. Here, we identified PTP4A3, a protein tyrosine phosphotase, as a novel negative regulator of LPS-induced LITAF/TNF-alpha production. PTP4A3 exerts its negative role by dephosphorylating p38 alpha MAPK in response to LPS stimulation of primary macrophages. PTP4A3 expression is upregulated in primary macrophages. Further structure-function analysis revealed that a unique short peptide (PIMAP39) derived from PTP4A3 is capable of mimicking the functionality of full-length PTP4A3 to selectively dephosphorylate p38 alpha and indirectly suppress LPS-induced LITAF-STAT6B complex when it is translocated from the cytoplasmic region to the nucleus of the cell. Treatment of mice with PIMAP39 significantly attenuates the severity of adverse host responses to LPS stimulation, and in some cases provides complete resistance to a lethal dose of LPS due to suppression of TNF-alpha production. All together, these results reveal a previously unrecognized role for the PTP4A3 pathway in response to LPS.


Ultra high performance liquid chromatography with tandem mass spectrometry for rapid separation and identification of main constituents in Chinese herbal formula Xuan Hu Suo San.
Xuan Hu Suo San (XHSS) is a traditional Chinese medicine that has been extensively applied in the treatment of osteoarthritis for many years, however, its chemical composition has not yet been elucidated. Thus, a rapid, efficient, and precise method based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied in both positive- and negative-ion modes to rapidly separate and identify the main chemical ingredients in XHSS for the first time. Finally, with the optimised separation and detection method, a total of 57 compounds were simultaneously separated within 13 min, among which 14 compounds were confirmed by comparing retention time and MS data with reference standards and others were tentatively identified by comparing with reference literatures. This rapid and sensitive approach is highly useful for the identification and characterisation of chemical constituents, and provides fundamental and extensive information supporting further metabolic and pharmacokinetic studies of XHSS.


[Therapy of High Risk Patients After Decompensation of Heart Failure Under NT-proBNP Control. Main Results].
to compare efficacy of treatment of high risk patients after acute decompensation (AD) of chronic heart failure (CHF) based on monitoring of NT-proBNP concentration and standard treatment. Patients (n=100) with class III-IV CHF and left ventricular ejection fraction (LV EF) <40% due to ischemic heart disease (IHD), dilated cardiomyopathy (DCMP), or arterial hypertension (AH) after compensation of HF before discharge were distributed into groups of low (NT-proBNP <1400 picog/ml, n=30) or high (NT-proBNP more or equal 1400 picog/ml, n=70) risk. High risk patients were randomized into 2 treatment groups: NT-proBNP based (group I, n=35) and standard (group II, n=35) therapy. At study closure we formed another group consisting of group I and II participants noncomplaint with study protocol (group NC, n=10). Groups practically did not differ by main clinical functional characteristics. Aim of treatment was lowering of NT-proBNP level below 1000 picog/ml or more or equal 50% from baseline. At discharge median NT-proBNP concentration was 3750.0 (2224.0; 6613.0), 2783.0 (2021.5; 4827.5), and 2162.0 (1684.5; 5750.0) picog/ml in groups I, II, and NC, respectively (=0.315). At study entry all group I and II patients received combination of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, -adrenoblockers, antagonists of mineralocorticoid receptors. After 6 months changes of doses of neuro-hormonal modulators in group I were more pronounced than in group II. NT-proBNP concentration decreased by 53% down to 1585.5 (976,6; 2742,5) picog/ml, =0.001, and by 10.2% in groups I and II, respectively (between group =0.001). In group I compared with II we observed more pronounced improvement of clinical functional indicators, quality of life, and parameters of systolic and diastolic LV function (<0.05), fewer cardiovascular deaths (4 vs. 10, =0.033) and repeat decompensations and rehospitalizations because CHF (4 vs. 14, =0.007). Compared with standard therapy long-term NT-proBNP guided treatment of high risk patients significantly significantly decreased rate of CV deaths and repeat decompensations and rehospitalizations because CHF, and more effectively influenced clinical and functional state, quality of life and main echocardiographical parameters of LV systolic and diastolic function.


Contrasting patterns of DNA strand breakage and ADP-ribosylation-dependent DNA ligation during granulocyte and monocyte differentiation.
Previous studies have shown that structural changes in DNA, including the ligation of pre-existing DNA breaks and the opening and closure of new breaks, occur shortly after exposure of granulomonocytic precursors (CFU-GM) to granulocyte-macrophage colony stimulating activity (GM-CSA). Monocytic differentiation of CFU-GM is selectively inhibited by compounds known to inhibit the nuclear enzyme ADP-ribosyl transferase (ADPRT). Since this enzyme, which transfers ADP-ribose units to chromatin proteins, is known to activate DNA ligase, we attempted to determine whether ligation of one or both types of DNA break is required for monocytic differentiation. Breaks in DNA were examined using the nucleoid sedimentation technique in which DNA breaks cause loss of DNA supercoiling in nucleoids and concomitant changes in their sedimentation through neutral sucrose gradients. We here report that two distinct patterns of DNA strand breakage and ligation are associated with differentiation to the granulocyte and monocyte lineages. Monocytic inducers (phorbolester and vitamin D3) predominantly produce closure of pre-existing strand breaks, whereas granulocytic inducers (granulocyte colony stimulating activity, G-CSA; retinoic acid) cause opening and closure of new breaks. Only ligation of the pre-existing breaks is highly sensitive to inhibition by 3-methoxybenzamide (a potent ADPRT inhibitor), and only monocytic differentiation is impaired by addition of this compound. These findings suggest that DNA structural changes may be directly involved in granulocyte-macrophage switching.


Three phosphatidylglycerol-phosphate phosphatases in the inner membrane of Escherichia coli.
The phospholipids of Escherichia coli consist mainly of phosphatidylethanolamine, phosphatidylglycerol (PG), and cardiolipin. PG makes up ∼25% of the cellular phospholipid and is essential for growth in wild-type cells. PG is synthesized on the inner surface of the inner membrane from cytidine diphosphate-diacylglycerol and glycerol 3-phosphate, generating the precursor phosphatidylglycerol-phosphate (PGP). This compound is present at low levels (∼0.1% of the total lipid). Dephosphorylation of PGP to PG is catalyzed by several PGP-phosphatases. The pgpA and pgpB genes, which encode structurally distinct PGP-phosphatases, were identified previously. Double deletion mutants lacking pgpA and pgpB are viable and still make PG, suggesting the presence of additional phosphatase(s). We have identified a third PGP-phosphatase gene (previously annotated as yfhB but renamed pgpC) using an expression cloning strategy. A mutant with deletions in all three phosphatase genes is not viable unless covered by a plasmid expressing either pgpA, pgpB, or pgpC. When the triple mutant is covered with the temperature-sensitive plasmid pMAK705 expressing any one of the three pgp genes, the cells grow at 30 but not 42 °C. As growth slows at 42 °C, PGP accumulates to high levels, and the PG content declines. PgpC orthologs are present in many other bacteria.


Effect of Parasitoid: Host Ratio and Group Size on Fitness of Spathius galinae (Hymenoptera: Braconidae): Implications for Mass-Rearing.
Producing insect natural enemies in laboratories or insectaries for biological pest control is often expensive, and developing cost-effective rearing techniques is a goal of many biological control programs. Spathius galinae Belokobylskij and Strazenac (Hymenoptera: Braconidae), a newly described ectoparasitoid of emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), is currently being evaluated for environmental introduction in the United States to provide biological control of this invasive pest. To improve mass-rearing outcomes for S. galinae, we investigated the effects of parasitoid: host ratio and parasitoid and host group size (density) on parasitoid fitness. Our results showed that when 1 emerald ash borer larva was exposed to 1, 2, 4, or 8 female parasitoids, parasitism rate was positively associated with increasing parasitoid: host ratio, while brood size, sex ratio, and fitness estimates of progeny were not affected. When a constant 1:1 parasitoid: host ratio was used, but group size varied from 1 female parasitoid and 1 host, 5 parasitoids and 5 hosts, 10 of each, and 20 of each in same size rearing cages, parasitism rates were highest when at least 5 females were exposed to 5 host larvae. Moreover, the number of progeny produced per female parasitoid was greatest when group size was 10 parasitoids and 10 hosts. These findings demonstrate that S. galinae may be reared most efficiently in moderately high-density groups (10 parasitoids and hosts) and with a 1:1 parasitoid: host ratio.


Equality in adults' oral health in Norway. Cohort and cross-sectional results over 33 years.
To assess social inequality in dental clinical parameters from 1973 to 2006. Samples from two birth-cohorts born between 1929-1938 and 1959-1960, respectively, and 35-44-year-olds were drawn in 1973, 1983, 1994 and in 2006 in the county of Nord-Trøndelag in Norway. Standard procedures were followed all the time. The examination comprised caries and caries treatment experience by DMF criteria and a questionnaire. Length of education in years was divided into quartiles in 1983, 1994 and 2006 to analyse the association between social status and clinical parameters. Statistical analyses were conducted within the same study year and between the years 1983 and 2006 by descriptive statistics and anova. The study showed that the DMFT/S index increased in the two birth-cohorts from 1973 to 1983 where after fewer changes occurred. However, there was a great improvement in oral health among 35-44-year old during the period from 1973 to 2006. The inequalities observed in 1983 remained or decreased and there was equality in number of present teeth all the time. The DMF results from the birth-cohorts showed that if social differences appear at an early age, they will persist in the cohorts the next 30 years and more. This is mainly because of the irreversibility of the DMF registrations. Social inequality was reduced but found in some indicators of dental status in 2006. Part of it can be explained by the insensitivity of the applied indexes. There is still a social divide in oral health and it affects elderly more than younger adults.


Morphological and functional maturity of the oral jaws covary with offspring size in Trinidadian guppies.
Large size of individual offspring is routinely selected for in highly competitive environments, such as in low-predation populations of the Trinidadian guppy (Poecilia reticulata). Large guppy offspring outcompete their smaller conspecifics, but the functional mechanisms underlying this advantage are unknown. We measured jaw kinematics during benthic feeding and cranial musculoskeletal morphologies in neonates and juveniles from five populations of Trinidadian guppy and found that both kinematics and morphologies vary substantially with neonatal size. Rotation at the intramandibular joint (IMJ), but not the quadratomandibular joint (QMJ), increases with size among guppy offspring, from 11.7° in the smallest neonates to 22.9° in the largest neonates. Ossification of the cranial skeleton varies from 20% in the smallest neonates to 90% in the largest. Relative to standard length (SL; jaw tip to caudal fin base distance), the surface area of jaw-closing musculature scales with positive allometry (SL2.72) indicating that muscle growth outpaces body growth. Maximum gape also scales with positive allometry (SL1.20), indicating that larger neonates are capable of greater jaw excursions. These findings indicate that size is not the sole adaptive benefit to producing larger offspring; maturation provides a potential functional mechanism underlying the competitive advantage of large offspring size among Trinidadian guppies.


Postoperative methicillin-resistant Staphylococcus aureus enteritis following hysterectomy: a case report and review of the literature.
Following a hysterectomy a 43-year-old woman developed colicky abdominal pain and profuse postoperative diarrhoea. Examination was unremarkable and initial investigations revealed a normal plain abdominal X-ray initially, but later there was some small bowel dilatation and evidence of raised inflammatory markers. No cause was identified at exploratory laparotomy 2 days post operation. Flexible sigmoidoscopy was normal. The patient was empirically treated with oral vancomycin for presumed Clostridium difficile diarrhoea, although subsequent stool cultures were negative for the usual intestinal pathogens and C. difficile toxin. The diarrhoea persisted for 9 days. By day 10 stool cultures had grown methicillin-resistant Staphylococcus aureus, establishing the diagnosis. To our knowledge this is the first report of methicillin-resistant S. aureus enteritis following hysterectomy.


Potential Use of Classroom Response Systems (CRS, Clickers) in Foods, Nutrition, and Dietetics Higher Education.
Although hundreds of articles have been published about the use of classroom response systems (CRS, clickers) in higher education, few address the use in foods, nutrition, and dietetics courses, especially upper-division, major courses. This technology has the potential to increase student engagement, motivation, assessment, and, possibly, learning. Thoughtfully designed questions may stimulate discussions, especially about challenging nutrition topics. This article presents the viability and potential benefits for the use of CRS in foods, nutrition, and dietetics classes through a brief literature summary, overview of the author's experiences, and guidance for implementing this technology.


A 3 trocar technique for transperitoneal laparoscopic nephrectomy.
Additional trocars and retractor instruments may enhance the risk of iatrogenic injuries during laparoscopic nephrectomy. We describe a modified technique of laparoscopic nephrectomy requiring only 3 ports of entry and no extra instruments instead of the 5 ports, 2 of which are used for retractors, usually required. With the patient in full flank position a 10 mm. trocar is inserted between the umbilicus and subcostal margin, a 5 mm. trocar is placed subcostal in the midclavicular line and a 12 mm. trocar is inserted over the iliac crest in the anterior axillary line. The first step is incision of the line of Toldt and medial reflection of the colon. During the second step of vascular controls the posterosuperior attachments of the kidney are left untouched, keeping the renal vessels stretched, with no need for an extra instrument. The third step consists of severing the remaining posterior and superior attachments of the kidney followed by specimen retrieval. A total of 14 consecutive patients underwent laparoscopic nephrectomy with this technique. All 14 procedures were completed without an additional port. There were no intraoperative or postoperative complications, except 1 abdominal wall hematoma. Mean operating time was 120 minutes (range 70 to 230) and mean hospital stay was 5 days (range 3 to 7). Transperitoneal laparoscopic nephrectomy with laparoscopic access limited to 3 trocars is a reliable and safe technique.


Effects of pitch spatial references on players' positioning and physical performances during football small-sided games.
The aim of this study was to identify the effects of adding spatial references during football small-sided games in youth players' tactical and physical performance. Twelve under-15 players performed a Gk+ 6v6+ Gk game under two playing conditions: (i) without spatial references (CONTROL condition); (ii) with spatial references, by dividing equally the pitch into three corridors and three sectors (experimental situation, LINES). Players' positional data was used to compute time-motion and tactical-related variables. The results revealed that performance under LINES situation increased the regularity in the zones occupied (~14%, Cohen's d: 0.5; ±0.3; p = 0.003) and in the distance between teammates' dyads (~19%, 0.9; ±0.2; p < 0.001). Oppositely, LINES condition decreased the longitudinal synchronization of players' displacements (0.4; ±0.2; p = 0.002), players' average speed (0.5; ±0.3; p = 0.002) and distance covered at lower (0.9; ±0.3; p < 0.001) and moderate speed (0.5; ±0.3; p < 0.001). Adding spatial references seems to promote a more structured pattern of play and increase positional regularity. However, coaches should be aware that this constraint may decrease the synchronization between players. Overall, these findings may be generalized to most invasion team sports.


[Treatment strategy for patients, with locally advanced non-small cell lung cancer].
A total of 89 patients with locally advanced lung cancer (pT3-4N0-1) underwent pulmonary resection from April 1994 to April 2003 at our institutions. The overall 5-year survival rate of the 89 patients was 35.5%. No significant difference in the 5-year survival rate was found according to the following variables: histologic type, type of operation, number of resected organs, performance of adjuvant therapy and pulmonary function. In patients with pN1 disease, when patients with nodal metastasis were divided into patients with hilar (# 10) or lobar (# 11 approximately 13) metastasis, the survival rate of lobar metastasis group was superior to those of hilar metastasis group, but not significantly. In patients with pN1 disease, 5 patients were survived for more than 1,000 days. The histology was squamous cell carcinoma in 4 cases. According to the characteristics of pN1 involvement, all cases was involved only a single station.