Using Spectroscopy to Guide the Adaptation of Aptamers into Electrochemical Aptamer-Based Sensors.
Electrochemical aptamer-based (EAB) sensors utilize the binding-induced conformational change of an electrode-attached, redox-reporter-modified aptamer to transduce target recognition into an easily measurable electrochemical output. Because this signal transduction mechanism is single-step and rapidly reversible, EAB sensors support high-frequency, real-time molecular measurements, and because it recapitulates the reagentless, conformation-linked signaling seen in vivo among naturally occurring receptors, EAB sensors are selective enough to work in the complex, time-varying environments found in the living body. The fabrication of EAB sensors, however, requires that their target-recognizing aptamer be modified such that (1) it undergoes the necessary binding-induced conformational change and (2) that the thermodynamics of this "conformational switch" are tuned to ensure that they reflect an acceptable trade-off between affinity and signal gain. That is, even if an "as-selected" aptamer achieves useful affinity and specificity, it may fail when adapted to the EAB platform because it lacks the binding-induced conformational change required to support EAB signaling. In this paper we reveal the spectroscopy-guided approaches we use to modify aptamers such that they support the necessary binding-induced conformational change. Specifically, using newly reported aptamers, we demonstrate the systematic design of EAB sensors achieving clinically and physiologically relevant specificity, limits of detection, and dynamic range against the targets methotrexate and tryptophan.


Sumatriptan nasal spray for migraine: a review of studies in patients aged 17 years and younger.
This review considers the epidemiology, clinical manifestations and functional consequences of migraine in children and adolescents and surveys the studies establishing the efficacy and tolerability of sumatriptan nasal spray in this patient population. Although therapeutic advances in paediatric and adolescent migraine have lagged behind those in adult migraine, the first systematic studies of migraine medications in young patients have brought about progress in the past five years. These studies show that therapeutic approaches suitable for adult patients are not always applicable to paediatric and adolescent patients. Because of the unique characteristics of paediatric and adolescent migraine, it has been difficult to demonstrate in young patients the efficacy of oral sumatriptan and other triptan tablets, which are the medications of choice for adult migraine. With sumatriptan, this finding has proven to be a consequence of the form in which the drug was administered rather than the inherent properties of the drug. The availability of sumatriptan nasal spray allows the benefits of migraine-specific therapy to be extended to children and adolescents. In both well-controlled, single-episode studies and long-term, multiple-episode studies, sumatriptan nasal spray has been effective and well tolerated for the acute treatment of migraine in children and adolescents. Except for unpleasant taste, which is not significantly distressing to patients, sumatriptan nasal spray has a tolerability profile similar to thatof placebo in young patients.


Application of Precise Positioning for Sputum Expectoration in ICU Patients with Pulmonary Infection.
To determine the application value of precise positioning for sputum expectoration in intensive care unit (ICU) hospitalized patients with pulmonary infection (PI). A total of 183 patients with PI treated in the ICUs of Shengjing Hospital of China Medical University from June 2019 to June 2020 were divided into a control group (n = 91) and an observation group (n = 92), all of whom received conventional drug therapy. The control group was given routine nursing intervention, based on which, the observation group was supplemented with precise positioning for sputum expectoration. The 24-hour sputum volume, respiratory rate (RR), blood gas analysis indexes, inflammatory indicators, Clinical Pulmonary Infection Score (CPIS), Modified Medical Research Council (mMRC) dyspnea scale score, and quality of life (36-Item Short-Form Health Survey, SF-36) were observed in both arms before and after intervention. The incidence of adverse reactions was counted. The observation group showed better mMRC scores than the control group (P < 0.05). Compared with the control group, the sputum volume, RR, and CPIS score were lower, and the SF-36 score was higher in the observation group 7 days after intervention (P < 0.05). After intervention, the oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) were higher, while the carbon dioxide partial pressure (PaCO2), C-reactive protein (CRP), procalcitonin (PCT), and leukocyte count were lower in the observation group compared with the control group (P < 0.05). There was no significant difference in the incidence of complications between the two arms (P > 0.05). The application of precise positioning for sputum expectoration in nursing intervention of ICU patients with PI can alleviate the severity of PI and dyspnea, reduce inflammatory reaction, and improve the quality of life of patients.


Nanostructured n-ZnO / thin film p-silicon heterojunction light-emitting diodes.
Electroluminescence (EL) was obtained from a p-Si (100) thin film/nanostructured n-ZnO heterojunction diode fabricated by a simple dielectrophoresis (DEP) method. The Si substrate was pre-patterned with electrodes and an insulating separation layer by a standard photolithographic process. ZnO nanostructures were formed by a simple solution chemistry and subsequently transferred to the pre-patterned substrate. Application of the DEP force at a frequency of 100 kHz and 6 V peak-to-peak voltage allowed precise positioning of the ZnO nanostructures at the edge of the metal electrodes. The physically formed p-Si (100) thin film/nanostructured n-ZnO heterojunction displayed multi-color emission from the ZnO near band edge as well as emission from defective states within the ZnO band gap.


Actin filament morphology in living and nonliving cultured mesangial cells: formation and dissolution.
Mesangial cells are contractile and are believed to play a role in the regulation of glomerular filtration. Actin filaments constitute an integral part of the cytoskeleton of these cells. To visualize actin filaments in both living and fixed acetone-extracted (nonliving) mesangial cells, we have used the fluorophore nitrobenzoxadiazole-phallacidin. Under the fluorescence microscope, mesangial cells displayed continuous staining. Distinct linear structures running from one end to the other were actin filaments or stress fibers (SF). SF were rather feathery and of slightly curvilinear appearance in living versus fixed, acetone-extracted cells. Formation of SF started a 4 h, and the majority of the cells had well developed SF within 24 h. To find out whether adhesion to a substrate was necessary to SF formation, we plated mesangial cells on variable thickness of poly-HEMA(2-hydroxyethyl methacrylate). This plastic surface at a high concentration (10(-1) M) produces poor adherence of mesangial cells. At 10(-1) M of poly-HEMA, the cells were rounded even after 48 h and did not develop any SF. In contrast, at a lower concentration (10(-4) M), mesangial cells were well spread, and SF were readily observed. These data indicated that spreading as well as formation of SF were directly related to the adhesion properties of the substrate. To evaluate the role of SF in contraction and relaxation of mesangial cells, we have first treated these cells with angiotensin II (5 x 10(-7) M) or dibutyryl cyclic adenosine monophosphate (5 x 10(-4) M) and then labeled them with nitrobenzoxadiazole phallacidin. Dibutyryl cyclic adenosine monophosphate caused dissolution of SF.(ABSTRACT TRUNCATED AT 250 WORDS)


New era in treatment for phenylketonuria: Pharmacologic therapy with sapropterin dihydrochloride.
Oral administration of sapropterin hydrochloride, recently approved for use by the US Food and Drug Administration and the European Commission, is a novel approach for the treatment of phenylketonuria (PKU), one of the most common inborn errors of metabolism. PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Contemporary therapy is based upon restriction of dietary protein intake, which leads to reduction of blood phenylalanine levels. This therapy is difficult to maintain throughout life, and dietary noncompliance is commonplace. Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. In a subset of individuals with PAH deficiency, sapropterin administration leads to reduction in blood phenylalanine levels independent of dietary protein. For these individuals, sapropterin is an effective novel therapy for PKU.


Solitary lumbar osteochondroma presenting with spinal cord compression.
We report a case of a middle-aged woman with a solitary osteochondroma of the L2 right lamina with intraspinal extension and spinal cord compression. The case is unusual in terms of localisation and age at clinical presentation. In fact, spinal osteochondromas as solitary lesions-especially when affecting the lumbar segment-are rare tumours of a maturing adolescent skeleton, infrequently affecting the neurological structures, because most of the lesions grow out of the spinal canal. Although unusual, they should be considered in the differential diagnosis. Prompt and accurate radiological investigations are important in planning appropriate management. Surgical total excision is the best treatment modality to remove spinal cord and/or nerve root compression, and to avoid the risk of recurrence or malignant transformation.


Clinical outcomes of SeQuent Please paclitaxel-coated balloons for de novo small coronary artery lesion in a Japanese multicenter post-approval registry.
Drug-coated balloon (DCB) angioplasty has emerged as an effective management strategy worldwide. In June 2016, DCB became available for the treatment of de novo small coronary lesions in Japan; however, there has been no multicenter analysis in a post-approval real-world clinical setting to date. The aim of this study was to evaluate the efficacy of DCB for de novo small coronary lesions based on a Japanese multicenter registry. From June 2016 to July 2017, a total of 111 lesions (102 patients) treated with DCB for de novo small coronary lesions were enrolled at six Japanese institutions. The primary endpoint was the rate of target lesion revascularization (TLR) at 12 months. Angiographic follow-up endpoints were binary restenosis and late lumen loss (LLL). Clinical follow-up data at 12 months were available for 106 lesions, excluding five lesions that required bailout stenting. The TLR rate was 5.7% (6/106 lesions). No cardiac death or target lesion thrombosis was observed. The binary restenosis rate was 14.4% and LLL was 0.0017 ± 0.37 mm. DCB angioplasty for de novo small coronary lesions in the real-world environment in Japan is effective with acceptable 12-month outcomes.


Post-ablative serum thyroglobulin is an independent predictor of recurrence in low-risk differentiated thyroid carcinoma: a 16-year follow-up study.
To study whether post-surgical and/or post-ablative thyroglobulin (Tg) concentrations may serve as independent predictors of disease recurrence in patients treated for TNM stage I or II well-differentiated thyroid carcinoma (WDTC). An observational retrospective study with a median follow-up of 16 years (range 10-24). Post-operative and post-ablative Tg concentrations, age, tumour size, local infiltration and nodal metastasis at primary surgery as well as disease recurrences and cancer-specific deaths were evaluated in 495 low-risk (TNM stages I and II) patients, the majority of whom had total thyroidectomy and radioactive iodine remnant ablation as initial treatment. Fifty-one patients (10.3%) experienced disease recurrence during follow-up. In multiple logistic regression analysis, post-ablative Tg concentrations (odds ratio (OR) 3.72, confidence interval (CI) 1.71-8.05, P=0.0009) and local infiltration on primary surgery (OR 2.66, CI 1.03-6.90, P=0.04) were the only independent predictors of recurrence. Post-ablative Tg concentration is a strong predictor of disease recurrence in WDTC.


The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.
Charcot-Marie-Tooth disease comprises a heterogeneous group of hereditary neuropathies which fall into two main groups: demyelinating CMT1 with reduced nerve conduction velocity and axonal CMT2 with normal nerve conduction velocity. The neuropathological features correspond in most cases to this classification. Four genes were recently identified to cause autosomal dominant CMT2, including the neurofilament light gene. Thus far, only few mutations have been reported in neurofilament light involving eight amino acids of the gene. We identified a novel mutation, Glu397Lys, in a conserved motive signaling the end of the rod domain. The affected family members from three generations showed strikingly different clinical phenotypes, including weakness of the lower extremities, foot deformities, and deafness. The mutation was associated with nerve conduction velocities ranging from 27 m/s in a 25-year-old female to 43 m/s in an 82-year-old male in the lower extremity motor nerves. Sural nerve biopsies of two affected subjects were analyzed by light and electron microscopy. The pathological changes consisted of a reduction of predominantly large myelinated nerve fibers and various stages of onion bulb formation as typically seen in CMT1. This correlative study further confirms that neurofilament light gene mutations cause a wide clinical spectrum. Thus, analysis of the neurofilament light gene should not be restricted to pure axonal neuropathies.


Triton X-100-induced lipoteichoic acid release is correlated with the methicillin resistance in Staphylococcus aureus.
We previously reported that Triton X-100 (TRX) reduced methicillin resistance in Staphylococcus aureus, although the degree of reduction varied among strains. One of the biological effects of TRX on S. aureus cells was enhancement of lipoteichoic acid (LTA) release. We investigated the correlation between the amount of LTA released and the degree of reduction in methicillin resistance induced by TRX. The strains showing the greatest reduction of methicillin resistance released the largest amount of LTA, compared to those showing slight or moderate reduction. A mutant whose resistance was not affected by TRX did not increase its release of LTA. These findings suggest that LTA release is associated with a reduction in methicillin resistance in the presence of TRX.


[Management of rejection following heart transplantation using oral steroid medication].
After 47 orthotopic heart transplantations with long-term immunosuppression (cyclosporin A, 3-10 mg/kg; azathioprine, 1-2 mg/kg; prednisolone 0.1 mg/kg) there were 306 episodes of acute rejection. In 44 of these (14.8%) the oral prednisolone dosage was increased, from a mean of 10.8 +/- 2.95 mg/d to 36.6 +/- 7.2 mg/d, followed by stepwise reduction to the original maintenance dose. Compared with the customary intravenous bolus administration (1.0 g/d for three days: success rate 89%), the oral schedule was successful in 33 of the 44 episodes of rejection (75%). It is concluded that in selected patients acute rejection episodes after heart transplantation can be successful treated by an increase in the oral dose of steroids without changing the dosage of the other two immunosuppressive drugs.


Magnetic resonance imaging of the spine.
Low back and neck pain are common and result in significant patient disability and health care expenditure. When conservative treatment fails or worrisome clinical findings are present, magnetic resonance imaging (MRI) is the imaging modality of choice to assess the cause and complicating features of spine pain. There are many potential aetiologies of spine pain with similar clinical presentation, including degenerative changes, infection, and insufficiency and pathologic fractures. MRI allows for the differentiation of these sources of spine pain and potential complicating features, permitting the appropriate direction of therapy.


Facile Multiscale Patterning by Creep-Assisted Sequential Imprinting and Fuel Cell Application.
The capability of fabricating multiscale structures with desired morphology and incorporating them into engineering applications is key to realizing technological breakthroughs by employing the benefits from both microscale and nanoscale morphology simultaneously. Here, we developed a facile patterning method to fabricate multiscale hierarchical structures by a novel approach called creep-assisted sequential imprinting. In this work, nanopatterning was first carried out by thermal imprint lithography above the glass transition temperature (Tg) of a polymer film, and then followed by creep-assisted imprinting with micropatterns based on the mechanical deformation of the polymer film under the relatively long-term exposure to mechanical stress at temperatures below the Tg of the polymer. The fabricated multiscale arrays exhibited excellent pattern uniformity over large areas. To demonstrate the usage of multiscale architectures, we incorporated the multiscale Nafion films into polymer electrolyte membrane fuel cell, and this device showed more than 10% higher performance than the conventional one. The enhancement was attributed to the decrease in mass transport resistance because of unique cone-shape morphology by creep-recovery effects and the increase in interfacial surface area between Nafion film and electrocatalyst layer.


Altered fronto-cerebellar connectivity in alcohol-naïve youth with a family history of alcoholism.
Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA), related to fcMRI. FH+youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+youth through atypical control processing.


Comparative effectiveness of the cholera toxin B subunit and alkaline phosphatase as carriers for oral vaccines.
The purpose of this study was to determine whether the B subunit of cholera toxin (CtxB) has adjuvant activity over and above serving as a carrier protein for orally administered vaccines. An oligonucleotide that encodes an antigenic determinant (GtfB.1) from the glucosyltransferase B gene (gtfB) of Streptococcus mutans was genetically fused to the 5' terminus of either the CtxB gene (ctxB) or the Escherichia coli alkaline phosphatase gene (phoA). The resulting chimeric proteins were expressed in a phoA mutant strain of E. coli and then purified. The antigenicities of the proteins were confirmed by immunoblotting analysis using antisera specific for GtfB, CtxB, or PhoA. An equimolar amount of peptide on each carrier was administered by gastric intubation to mice three times at 10-day intervals. Antibody titers to the peptide, CtxB, and PhoA (in the serum, intestine, vagina, saliva, and bronchus) were determined by enzyme immunoassay. Antibody to the peptide was detected only in the sera of mice immunized with the peptide fused to CtxB. No antipeptide antibody was detected in mice immunized with the peptide fused to PhoA. The lack of detectable levels of antipeptide antibody in intestinal lavage fluid was attributed to dilution of the sample beyond the sensitivity of the assay. This was confirmed by cultivation of Peyer's patch and mesenteric lymph node tissue from mice orally immunized with the GtfB.1::CtxB chimera. Using this method, antipeptide antibody was detected in the culture fluid. We conclude that CtxB possesses unique properties that allow it to act as more than a simple carrier protein.


Infectious stunting syndrome of chickens in Great Britain: field and experimental studies.
Field cases of infectious stunting syndrome, and experimental cases produced by inoculating 1-day-old chicks with intestinal homogenates obtained from field cases, were studied. In the intestines of stunted 4- to 6-day-old chickens there was degeneration and necrosis of enterocytes in the crypts of Lieberkuhn and an infiltration of macrophages and lymphocytes into the lamina propria. Some crypts were distended with necrotic and degenerating cells, including heterophils, and there was hypertrophy of enterocytes in the crypts and zones of maturation. The proximal jejunum was more severely affected than other sections of the small intestine, and up to 25% of the crypts were involved. Cold stress increased the severity and extent of these intestinal lesions at 5 days of age. In chickens more than 8 days of age there were a few cystic crypts lined by cuboidal to squamous epithelium, and an apparent loss of crypts. Necrosis and degeneration of epithelial cells lining pancreatic ducts and ductules were observed in 9% of field cases aged 4 to 6 days and 2% of experimentally infected chickens at 5 days of age. Pancreatic degeneration was noted in 35% of field cases aged more than 13 days of age, but in only 0.75% of experimentally infected cases at 14 days of age. Five-day-old experimentally infected broiler chickens had a greater intestinal length per unit live-weight than controls, and they also had a greater intestinal weight per unit length. In field cases, the greatest intestinal length per unit live-weight was in severely stunted chickens with pancreatic degeneration. Osteodystrophy was a frequent, but not consistent, feature in poorly grown birds in many broiler flocks over 2 weeks of age which had infectious stunting syndrome, but it was not prominent in experimental cases.


Does social capital influence preferences for aging in place? Evidence from urban China.
This study investigated the relationships between social capital and preferences for aging in place among older urban adults in eastern China. Quota sampling was used to recruit 456 respondents aged 60 and older from Gusu District, Suzhou City, in 2015. Random-effects logistic regression was used to test the proposed model. Respondents who had better quality family social capital, a higher level of social trust, and more organization memberships were more likely to choose to live in local communities, even after we controlled for individual characteristics. The findings highlight the important role of both family and community social capital in influencing preferences for aging in place among older adults in urban China. This is particularly important for developing long-term care systems for older adults living in naturally occurring retirement communities.


Functional characterization of three clones of the human intestinal Caco-2 cell line for dietary lipid processing.
We aimed to improve the use of the human intestinal Caco-2 cell line for studying dietary lipid and cholesterol processing by using isolated pure clones (Chantret et al. 1994). Three clones (TC7, PD7 and PF11) were grown as monolayers on semi-permeable filters and compared for cell viability, fatty acid and cholesterol apical uptake or basolateral secretion, apolipoprotein B-48 basolateral secretion and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. The TC7 clone showed the best viability upon apical incubation with mixed micelles and should be preferred for routine work. Short-term (3.0 h) rates of apical uptake of cholesterol were not different with the three clones, whereas the rate of apical uptake of oleic acid (18:1) was lower (P<0.05) with PF11 (250.6 nmol/mg) and the basolateral secretion of cholesterol and oleic acid was lower with the TC7 clone (0.40 and 29.1 nmol/mg respectively). The secretion of apolipoprotein B-48 basolaterally was about 2-fold lower than from PD7 clone. The basal levels of HMG-CoA reductase activity were significantly different (P<0.05; TC7>PF11 >PD7). The down-regulation of the enzyme activity was moderate (range 13.8-21.0%) and comparable in the presence of apical micellar cholesterol, but was much marked upon basolateral incubation with LDL (range 34.0-53.6%), especially for the PD7 clone. In conclusion, the Caco-2 clones characterized here proved to be particularly suitable for studying lipid nutrients processing. Because these three clones exhibit some different metabolic capabilities, they provide a new tool to study intestinal response to lipid nutrients.


Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma.
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) has been shown to stimulate the growth of various cell types in an autocrine or paracrine manner. Although HB-EGF is widely expressed in tumors when compared with normal tissue, its contribution to cancer progression remains obscure. The objective of this study was to explore the effects of HB-EGF on proliferation, invasion activity and MMP-9 levels of an oral squamous cell carcinoma cell line, HSC3, in vitro. MTT assays, Matrigel invasion assays and RT-PCR in combination with RNA interference (RNAi) were used in this study. An RNAi-mediated decrease in HB-EGF expression reduced invasion activity and MMP-9 mRNA levels, but not proliferation, in HSC3 cells. The addition of purified HB-EGF to cell culture medium upregulated MMP-9 mRNA levels in HSC3 cells. Furthermore, the TACE inhibitor TAPI-2 or EGFR inhibitor AG1478 decreased MMP-9 mRNA levels in HSC3 cells. These data indicate that HB-EGF released from HSC3 cells by TACE stimulates EGFR in an autocrine manner, which in turn activates invasion activity via MMP-9 upregulation.


Effectiveness of a universal health-promoting parenting program: a randomized waitlist-controlled trial of All Children in Focus.
Parenting programs have been highlighted as a way of supporting and empowering parents. As programs designed to promote children's health and well-being are scarce, a new health-promotion program, All Children in Focus, has been developed. The purpose of this trial was to evaluate the potential effectiveness of the program in promoting parental self-efficacy and child health and development, as well as to investigate possible moderators of these outcomes. A multicenter randomized waitlist-controlled trial was conducted. The trial included 621 parents with children aged 3-12 years. Parents were randomized to receive the intervention directly or to join a waitlist control group. Parents completed questionnaires at baseline, 2 weeks after the intervention, and 6 months post-baseline. To evaluate potential effects of the program, as well as any moderating variables, multilevel modeling with a repeated-measures design was applied. Parents in the intervention group reported that their self-efficacy (p < .001), as well as their perceptions of children's health and development (p < .05), increased 6 months post-baseline when compared with parents in the control group. One variable was found to moderate both outcomes: parents' positive mental health. Furthermore, parents' educational level and number of children moderated parental self-efficacy, while the children's age moderated child health and development. Having a poor positive mental health, a university-level education, more than one child in the family, and older children, made the families benefit more. In the first randomized controlled trial of All Children in Focus, we found that the program appears to promote both parental self-efficacy and children's health and development in a general population. Additionally, we found that families may benefit differently depending on their baseline characteristics. This contributes to an existing understanding of the advantages of offering universal parenting programs as a public health approach to strengthening families. However, further research is needed to investigate long-term effects and mediating variables, as well as the potential cost-effectiveness of the program. Current Controlled Trials: ISRCTN70202532. November 7th 2012.


Inherited disorders of brain neurotransmitters: pathogenesis and diagnostic approach.
Neurotransmitters (NTs) play a central role in the efficient communication between neurons necessary for normal functioning of the nervous system. NTs can be divided into two groups: small molecule NTs and larger neuropeptide NTs. Inherited disorders of NTs result from a primary disturbance of NTs metabolism or transport. This group of disorders requires sophisticated diagnostic procedures. In this review we discuss disturbances in the metabolism of tetrahydrobiopterin, biogenic amines, γ-aminobutyric acid, foliate, pyridoxine-dependent enzymes, and also the glycine-dependent encephalopathy. We point to pathologic alterations of proteins involved in synaptic neurotransmission that may cause neurological and psychiatric symptoms. We postulate that synaptic receptors and transporter proteins for neurotransmitters should be investigated in unresolved cases. Patients with inherited neurotransmitters disorders present various clinical presentations such as mental retardation, refractory seizures, pyramidal and extrapyramidal syndromes, impaired locomotor patterns, and progressive encephalopathy. Every patient with suspected inherited neurotransmitter disorder should undergo a structured interview and a careful examination including neurological, biochemical, and imaging.


Racial differences in potassium response to spironolactone in heart failure.
Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African-American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5 mg/d, with up-titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in African Americans; p < 0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.


Template-Assisted meta-C-H Alkylation and Alkenylation of Arenes.
To expand the scope of meta-functionalization, a pyrimidine-based template effective for the formation of β-aryl aldehydes and ketones, using allyl alcohols, by meta-C-H activation of benzylsulfonyl esters is described. In addition, α,β-unsaturated aldehydes were generated by in situ olefination and deprotection of allyl benzyl ethers. These new functionalizations at the meta-position of an arene have also been successfully implemented in benzylphosphonate, phenethyl carbonyl, and phenethylsulfonyl ester scaffolds. Key to these successful new functionalizations is the creation of an electropositive palladium center by accepting the electron cloud from the metal to the energetically low-lying π-orbitals of pyrimidine ring, and it favors coordination of allyl alcohol to the metal center.


Manganese/Copper Co-catalyzed Electrochemical Wacker-Tsuji-Type Oxidation of Aryl-Substituted Alkenes.
A manganese/copper co-catalyzed electrochemical Wacker-Tsuji-type oxidation of aryl-substituted alkenes has been developed. The process involves the use of 5 mol % MnBr2 and 7.5 mol % CuCl2, in 4:1 acetonitrile/water in an undivided cell at 60 °C, with 2.8 V constant applied potential. α-Aryl ketones are formed in moderate to excellent yields, with the advantages of avoidance of palladium as a catalyst and any external chemical oxidant in an easily operated, cost-effective procedure.


Molecular Pivot-Hinge Installation to Evolve Topology in Rare-Earth Metal-Organic Frameworks.
Linker desymmetrization has been witnessed as a powerful design strategy for the discovery of highly connected metal-organic frameworks (MOFs) with unprecedented topologies. Herein, we introduce molecular pivot-hinge installation as a linker desymmetrization strategy to evolve the topology of highly connected rare-earth (RE) MOFs, where a pivot group is placed in the center of a linker similar to a hinge. By tuning the composition of pivot groups and steric hindrances of the substituents on various linker rotamers, MOFs with various topologies can be obtained. The combination of L-SO2 with C2v symmetry and 12-connected RE9 clusters leads to the formation of a fascinating (4,12)-c dfs new topology. Interestingly, when replacing L-SO2 with a tetrahedra linker L-O, the stacking behaviors of RE-organic layers switch from an eclipsed mode to a staggered stacking mode, leading to the discovery of an intriguing hjz topology. Additionally, the combination of the RE cluster and a linker [(L-(CH3 )6 )] with more bulky groups gives rise to a flu topology with a new 8-c inorganic cluster. The diversity of these RE-MOFs was further enhanced through post-synthetic installation of linkers with various functional groups. Functionalization of each linker with acidic and basic units in the mesoporous RE-based PCN-905-SO2 allows for efficient cascade catalytic transformation within the functionalized channels.


Law 66/88 modifying the Protection of Maternity Law of 1987.
This Law amends the Cyprus Protection of Maternity Law of 1987 to provide that nine of the 12 weeks of mandatory maternity leave must be taken in the period starting two weeks before delivery. Law 68/88 modifies the Social Insurance Law to provide for 12 weeks of maternity allowance.


In vivo assessment of lipid peroxidation products associated with age-related neurodegenerative diseases.
Numerous in vitro and cell culture experiments indicate that oxidative damage decreases astrocyte glutamate transport activity, and it has been proposed that products of lipid peroxidation, particularly 4-hydroxy-2-nonenal, may contribute to neurodegenerative diseases via inhibition of glutamate or glucose transporter activity. We have directly tested the hypothesis that lipid peroxidation products impair glutamate and glucose transport in vivo. Lipid peroxidation products that irreversibly modify protein lysyl residues caused a two- to sixfold elevation in extracellular glutamate in striatum and cerebral cortex of both freely moving and anesthetized rats undergoing microdialysis. No concomitant change in extracellular glucose concentrations was observed. Furthermore, lipid peroxidation product-evoked extracellular glutamate appeared to be derived from nonneuronal sources. Our results demonstrate a biochemical mechanism whereby oxidative damage products can increase extracellular glutamate levels in vivo, providing support for the proposal that oxidative damage leads to inhibition of glutamate transport and thereby may contribute to the progression of neurodegenerative diseases.


FK-506 (fujimycin) reverses the multidrug resistance of tumor cells in vitro.
Cyclosporin A (CsA) and FK-506 have similar immunosuppressive activity profiles and cyclophilin-like intracellular targets. Since CsA can reverse the multidrug resistance of tumor cells showing P-glycoprotein-mediated drug efflux, the possible resistance-modulating activity of FK-506 was evaluated in vitro with multidrug-resistant P388 cells and their sensitive parental controls. Higher concentrations of FK-506 than CsA were needed to achieve a similar degree of chemosensitization, suggesting that FK-506 might interact less efficiently than CsA with the P-glycoprotein expressed in multidrug-resistant tumor cells. However, FK-506 was active on a broader range of concentrations than CsA, particularly because of direct cytostatic effects of CsA which appeared at concentrations only slightly higher than those required to show a significant resistance-modulating activity.


Fluidic embedding of additional macroporosity in alginate-gelatin composite structure for biomimetic application.
Biomimetic characteristics of hydrogel scaffold are tuned in this study utilizing the synergy of alginate, gelatin, and microfluidically embedded voids. Superposition of alginate and gelatin polymer networks results in additional rigidity, which can be tuned by introduction of voids, and thereby allowing faster release of pore pressure through movement of aqueous phase through the pore network. More importantly, voids enabled the cells to penetrate from the surface of seeding into the depth of the scaffold and proliferate there, as demonstrated for MDA MB 231 breast cancer cells. The uniform voids, generated by the microfluidic device, self-align creating uniform macroporosity within the gel structure, get readily filled by the media due to hydrophilicity, and extend the characteristics of composite uniformly across the entire scaffold.


[Pulmonary hypertension in patients with pure obstructive sleep apnea].
Patients with obstructive sleep apnoea (OSA) every night experience recurrent episodes of alveolar hypoxia. Alveolar hypoxia is the most potent pulmonary vasoconstrictor causing remodeling of pulmonary arteries and pulmonary hypertension. Development of pulmonary hypertension in patients with OSA is rather rarely observed but still discussed. We studied pulmonary haemodynamics, using Swan Ganz thermodilution catheter, in 67 patients (64 M and 3 F, mean age 45 years) with severe OSA (in full polysomnography mean AHI = 62) and normal pulmonary function data. We observed normal mean haemodynamic values at rest: PPA 15,8 mm Hg, PW 6.8 mm Hg, CO 5.6 L/min. PVR 150 dyn.sec.cm(-5). In 11 pts (16%) the pulmonary artery pressure at rest was elevated (PPA 23.9 mm Hg and PVR 234 dyn.sec.cm(-5)), they were younger, more obese and had higher number of apneic episodes per hour of sleep. During mild exercise (44 pts) PPA rose from 15.8 mm Hg to 29.8 mm Hg and was abnormally high in 17 pts. we observed pulmonary hypertension at rest in 16% patients with severe OSA, but during exercise in about 40%.


Novel lyssavirus in bat, Spain.
A new tentative lyssavirus, Lleida bat lyssavirus, was found in a bent-winged bat (Miniopterus schreibersii) in Spain. It does not belong to phylogroups I or II, and it seems to be more closely related to the West Causasian bat virus, and especially to the Ikoma lyssavirus.


[Borrelia burgdorferi Group: in-vitro antibiotic sensitivity].
Failures in the antibiotic therapy of Lyme disease have repeatedly been demonstrated by post-treatment isolations of the infecting borreliae. Analyses of the antibiotic susceptibility patterns of borreliae may help to understand the causes of such treatment failures and to develop new therapeutic regimens. The three subspecies of Borrelia burgdorferi known to be pathogenic for humans and to differ in their virulence and organ affinity possibly may also show divergent susceptibilities to some common antibacterial agents. In order to get real clues for such probable differences we compared the efficacy of six antimicrobial agents against 24 borrelial tick and skin isolates belonging to the three subspecies of B. burgdorferi sensu lato. In five comparative evaluations, some significantly different antibiotic sensitivity of the three borrelial species was found. The Borrelia burgdorferi sensu stricto isolates showed lower sensitivity to cephalosporin, tetracycline and ciprofloxacin as well as a higher sensitivity to erythromycin compared to the B. afzelii and B. garinii isolates. The B. garinii isolates proved to be more sensitive to penicillin in comparison to the B. burgdorferi s.s. and B. afzelii isolates. In the light of these data, treatment failures may be interpreted by serum and tissue levels of the antibiotic too low for an effective killing of the infecting Spirochetes. However, prolonged treatment regimens applying higher dosages of antibiotics, in order to get complete clearing of the infection, may be linked to aggravated side effects. Therefore, the combination of different antiborrelial agents with synergistic effect seems to be a meaningful alternative and should be included in future studies in vitro as well as in vivo.


A Natural Variation of Fumonisin Gene Cluster Associated with Fumonisin Production Difference in Fusarium fujikuroi.
Fusarium fujikuroi, a member of the Fusarium fujikuroi species complex, stands out as a rice bakanae disease pathogen with a high production of gibberellic acid. Not all, but some F. fujikuroi strains are known to produce a carcinogenic mycotoxin fumonisin. Fumonisin biosynthesis is dependent on the FUM cluster composed of 16 FUM genes. The FUM cluster was detected not only from a fumonisin producing strain, but also from a fumonisin nonproducing strain that does not produce a detectable level of fumonisin. Genetic mapping indicated the causative mutation(s) of fumonisin nonproduction is present in the FUM cluster of the fumonisin nonproducing strain. Comparative analyses of FUM genes between the fumonisin producing and the nonproducing strains and gene complementation indicated that causative mutation of fumonisin nonproduction is not a single occurrence and the mutations are distributed in FUM21 and FUM7. Our research revealed a natural variation in the FUM cluster involving fumonisin production difference in F. fujikuroi.


A structural DNA binding protein of African swine fever virus with similarity to bacterial histone-like proteins.
Here we describe an African swine fever virus (ASFV) protein encoded by the open reading frame 5-AR that shares structural and functional similarities with the family of bacterial histone-like proteins which include histone-like DNA binding proteins, integration host factor, and Bacillus phage SPO1 transcription factor, TF1. The ASFV 5-AR gene was cloned by PCR and expressed in E. coli. Monospecific antiserum prepared to the 5-AR bacterial expression product specifically immunoprecipitated a protein of approximately 11.6 kDa from ASFV infected swine macrophages at late times post infection. Additionally, the 5-AR expression product was strongly recognized by ASFV convalescent pig serum, indicating its antigenicity during natural infection. Cloned p11.6 bound both double and single stranded DNA-cellulose columns. Consistent with a DNA binding function, immunoelectronmicroscopy localized p11.6 to the virion nucleoid, To our knowledge, p11.6 is the first bacterial histone-like DNA-binding protein found in an animal virus or eukaryotic cell system.


Anatomy of the cavernous sinus region.
The cavernous region was examined in 20 fetuses, injected with Micropaque, and in 5 adults. The lateral wall of the cavernous region in fetuses was noticed to have four layers. The superficial membrane represents the dural sheath. The second membrane of dense connective tissue involves the trochlear nerve. The third layer, formed by loose connective tissue, involves the oculomotor nerve, and the ophthalmic and maxillary division. The fourth layer, which represents the lateral wall of the cavernous sinus, involves the abducent nerve. The meningohypophyseal trunk can be complete or incomplete. The inferolateral trunk and its branches were found to supply the cavernous portions of the mentioned cranial nerves. The obtained data make the anatomic basis for neurosurgical operations in the cavernous region.


Radiation-induced reactions via the lowest excited states in cinnamic acid crystals.
Radiation-induced reactions of cinnamic acid derivatives have been examined and compared with photoreactions in the crystalline state; all the reaction products were exactly the same as those of the photoreactions, indicating that the reactions proceed only via the lowest excited state to give [2 + 2] cycloadducts, E/Z isomerization products, or starting molecules.


[Large renal leiomyoma].
Renal leiomyomas are uncommon between renal tumors, and they have a benign mesenchymatous origin. Because of their low incidence, unspecific symptomatology an not well-defined iconographic semiology, they often raise problems with differential diagnosis from kidney masses, although they are often big size lessions. We report a patients with incidentally diagnosis of big solid left renal mass, who underwent radical nephrectomy resulting kidney pelvis leiomyoma. Diagnostic, histological and therapeutic aspects are briefly review in literature. Emphasis is made on the relevance of a high index suspicion considering big solid asymptomatic renal masses in middle-age women. Specially in renal tumors with well-defined limits and abscence of locoregional and systemic dissemination. We emphasized usefulness of Magnetic Angioresonance, immunohystochemical test and conservative surgery opportunity in small renal leiomyomas preoperatively confirmed.


MAP kinase phosphorylation of mSos1 promotes dissociation of mSos1-Shc and mSos1-EGF receptor complexes.
The mouse protein mSos1 has a central Ras guanine nucleotide exchange domain, and a long proline-rich C-terminal tail which contains several potential binding sites for the SH3 domains of the adaptor protein, Grb2. In fibroblasts, growth factor stimulation results in the recruitment of Grb2-mSos1 into complexes with activated receptors and cytoplasmic phosphoproteins such as Shc, which are apparently involved in Ras activation, and subsequently to an increase in mSos1 phosphorylation on serine and threonine. The catalytic and C-terminal domains of mSos1 contain several potential sites for phosphorylation by mitogen-activated protein kinases. In vitro, purified p42/p44 MAP-kinase selectively phosphorylated the C-terminal tail of mSos1. Comparative tryptic phosphopeptide mapping of mSos1 phosphorylated in vitro by MAP kinase and of mSos1 immunoprecipitated from EGF-stimulated cells, revealed several phosphopeptides in common. These common phosphorylation sites have been mapped to a region encompassing the first three proline (pro)-rich motifs in the tail of mSos1. Furthermore, a region of mSos1 containing the first two pro-rich motifs could associate with MBP kinase activity in vitro. Phosphorylation of mSos1 did not affect binding of Grb2 to mSos1, but appeared to decrease binding of the mSos1-Grb2 complex to Shc and the EGF-receptor. These findings suggest a potential inhibitory role for MAP-kinase in attenuating nucleotide exchange on Ras, by uncoupling mSos1 from membrane-bound receptor complexes that lead to Ras activation.


[Langerhans Cell Histiocytosis in adults].
Five cases of Langerhans' cell histiocytosis in adult patients were reviewed. Signs, symptoms, the course of the disease and methods of treatment were presented. Results of tests, including results of organ biopsies that provided definitive diagnosis in most cases, were also analysed.


Natural transformation of Acinetobacter sp. strain BD413 with cell lysates of Acinetobacter sp., Pseudomonas fluorescens, and Burkholderia cepacia in soil microcosms.
To elucidate the biological significance of dead bacterial cells in soil to the intra- and interspecies transfer of gene fragments by natural transformation, we have exposed the kanamycin-sensitive recipient Acinetobacter sp. strain BD413(pFG4) to lysates of the kanamycin-resistant donor bacteria Acinetobacter spp., Pseudomonas fluorescens, and Burkholderia cepacia. Detection of gene transfer was facilitated by the recombinational repair of a partially (317 bp) deleted kanamycin resistance gene in the recipient bacterium. The investigation revealed a significant potential of these DNA sources to transform Acinetobacter spp. residing both in sterile and in nonsterile silt loam soil. Heat-treated (80 degrees C, 15 min) cell lysates were capable of transforming strain BD413 after 4 days of incubation in sterile soil and for up to 8 h in nonsterile soil. Transformation efficiencies obtained in vitro and in situ with the various lysates were similar to or exceeded those obtained with conventionally purified DNA. The presence of cell debris did not inhibit transformation in soil, and the debris may protect DNA from rapid biological inactivation. Natural transformation thus provides Acinetobacter spp. with an efficient mechanism to access genetic information from different bacterial species in soil. The relatively short-term biological activity (e.g., transforming activity) of chromosomal DNA in soil contrasts the earlier reported long-term physical stability of DNA, where fractions have been found to persist for several weeks in soil. Thus, there seems to be a clear difference between the physical and the functional significance of chromosomal DNA in soil.


A domain of RecC required for assembly of the regulatory RecD subunit into the Escherichia coli RecBCD holoenzyme.
The heterotrimeric RecBCD enzyme of Escherichia coli is required for the major pathway of double-strand DNA break repair and genetic exchange. Assembled as a heterotrimer, the enzyme has potent nuclease and helicase activity. Analysis of recC nonsense and deletion mutations revealed that the C terminus of RecC is required for assembly of the RecD subunit into RecBCD holoenzyme but not for recombination proficiency; the phenotype of these mutations mimics that of recD deletion mutations. Partial proteolysis of purified RecC polypeptide yielded a C-terminal fragment that corresponds to the RecD-interaction domain. RecD is essential for nuclease activity, regulation by the recombination hotspot Chi, and high affinity for DNA ends. The RecC-RecD interface thus appears critical for the regulation of RecBCD enzyme via the assembly and, we propose, disassembly or conformational change of the RecD subunit.


Familial Kleine-Levin syndrome: two siblings with unusually long hypersomnic spells.
Kleine-Levin syndrome is a rare, sporadic disorder, with discrete spells of hypersomnolence occurring during adolescence, variously accompanied by megaphagia, behavioral changes, psychosis, and mild autonomic symptoms. Familial cases have not previously been reported. We describe 2 siblings who shared uncharacteristically prolonged episodes of hypersomnolence, and the HLA-DR2 haplotype. In one patient, levels of cerebrospinal fluid orexin (hypocretin) during an attack were normal. The presence of an increased sleep drive, despite the occurrence of large amounts of ostensibly restorative sleep, suggests the possible existence of a disorder of sleep satiety.


[Titanium porous-surface screw implant].
Titanium porous-surfaced screw implant was made by plasma-spray with Ti powder. The pore size was 80-300 microns. Two groups of implants were implanted in the mandibles of 15 dogs. Group A: porous-surfaced screw implant: Group B: smooth surface screw implant. The bone healing was evaluated by L. M. SEM. and shear strength testing. The results show that the osteo integration of two groups were completed after 12 weeks. The bone grew into porous surface. The shear strength of group A was significantly higher than that of group B.


Role of hepatic alpha- and beta-adrenergic receptor stimulation on hepatic glucose production during heavy exercise.
The role of catecholamines in the control of hepatic glucose production was studied during heavy exercise in dogs, using a technique to selectively block hepatic alpha- and beta-adrenergic receptors. Surgery was done > 16 days before the study, at which time catheters were implanted in the carotid artery, portal vein, and hepatic vein for sampling and the portal vein and vena cava for infusions. In addition, flow probes were implanted on the portal vein and hepatic artery. Each study consisted of a 100-min equilibration, a 30-min basal, a 20-min heavy exercise (approximately 85% of maximum heart rate), a 30-min recovery, and a 30-min adrenergic blockade test period. Either saline (control; n = 7) or alpha (phentolamine)- and beta (propranolol)-adrenergic blockers (Blk; n = 6) were infused in the portal vein. In both groups, epinephrine (Epi) and norepinephrine (NE) were infused in the portal vein during the blockade test period to create supraphysiological levels at the liver. Isotope ([3-3H]glucose) dilution and arteriovenous differences were used to assess hepatic function. Arterial Epi, NE, glucagon, and insulin levels were similar during exercise in both groups. Endogenous glucose production (Ra) rose similarly during exercise to 7.9 +/- 1.2 and 7.5 +/- 2.0 mg.kg-1.min-1 in control and Blk groups at time = 20 min. Net hepatic glucose output also rose to a similar rate in control and Blk groups with exercise. During the blockade test period, arterial plasma glucose and Ra rose to 164 +/- 5 mg/dl and 12.0 +/- 1.4 mg.kg-1.min-1, respectively, but were essentially unchanged in Blk. The attenuated response to catecholamine infusion in Blk substantiates the effectiveness of the hepatic adrenergic blockade. In conclusion, these results show that direct hepatic adrenergic stimulation does not participate in the increase in Ra, even during the exaggerated sympathetic response to heavy exercise.


DENOISING AND DEINTERLEAVING OF EPSI DATA USING STRUCTURED LOW-RANK MATRIX RECOVERY.
Echo-planar spectroscopic imaging (EPSI) sequence with spectrally interleaving is often used to rapidly collect metabolic MRI data. The main problem in using it on high field scanners is the presence of spurious peaks resulting from phase distortions between interleaves as well as the low signal to noise ratio. We introduce a novel structured low-rank framework for the simultaneous denoising and deinterleaving of spectrally interleaved EPSI data. The proposed algorithm exploits annihilation relations resulting from the linear predicability of exponential signals as well as due to uncorrected phase relations between interleaves. The algorithm is formulated as a structured nuclear norm minimization of a block Hankel matrix, derived from the interleaves. Experiments using hyperpolarized 13 C mouse kidney EPSI data demonstrate the ability of the algorithm to remove ghost peaks from EPSI data collected using bipolar readout gradients.


Estimating Bounds on Collisional Relaxation Rates of Spin-Polarized 87Rb Atoms at Ultracold Temperatures.
We present quantum scattering calculations for the collisional relaxation rate coefficient of spin-polarized 87Rb(f = 2,m = 2) atoms, which determines the loss rate of cold Rb atoms from a magnetic trap. Unlike the lighter alkali atoms, spin-polarized 87Rb atoms can undergo dipolar relaxation due to both the normal spin-spin dipole interaction and a second-order spin-orbit interaction with distant electronic states of the dimer. We present ab initio calculations for the second-order spin-orbit terms for both Rb2 and Cs2. The corrections lead to a reduction in the relaxation rate for 87Rb. Our primary concern is to analyze the sensitivity of the 87Rb trap loss to the uncertainties in the ground state molecular potentials. Since the scattering length for the a3Σ+u state is already known, the major uncertainties are associated with the X1Σ+g potential. After testing the effect of systematically modifying the short-range form of the molecular potentials over a reasonable range, and introducing our best estimate of the second-order spin-orbit interaction, we estimate that in the low temperature limit the rate coefficient for loss of Rb atoms from the f = 2,m = 2 state is between 0.4 × 10-15 cm3/s and 2.4 × 10-15 cm3/s (where this number counts two atoms lost per collision). In a pure condensate the rate coefficient would be reduced by 1/2.


Variations in Kinetic Properties of Ribulose-1,5-bisphosphate Carboxylases among Plants.
Studies of ribulose-1,5-bisphosphate (RuBP) carboxylase from taxonomically diverse plants show that the enzyme from C(3) and crassulacean acid metabolism pathway species exhibits lower K(m)(CO(2)) values (12-25 micromolar) than does that from C(4) species (28-34 micromolar). RuBP carboxylase from aquatic angiosperms, an aquatic bryophyte, fresh water and marine algae has yielded consistently high K(m)(CO(2)) values (30-70 micromolar), similar in range to that of the enzyme from C(4) terrestrial plants. This variation in K(m)(CO(2)) is discussed in relation to the correlation between the existence of CO(2)-concentrating mechanisms for photosynthesis and the affinity of the enzyme for CO(2). The K(m)(RuBP) of the enzyme from various sources ranges from 10 to 136 micromolar; mean +/- sd = 36 +/- 20 micromolar. This variation in K(m)(RuBP) does not correlate with different photosynthetic pathways, but shows taxonomic patterns. Among the dicotyledons, the enzyme from crassinucellate species exhibits lower K(m)(RuBP) (18 +/- 4 micromolar) than does that from tenuinucellate species (25 +/- 7 micromolar). Among the Poaceae, RuBP carboxylase from Triticeae, chloridoids, andropogonoids, Microlaena, and Tetrarrhena has yielded lower K(m)(RuBP) values (29 +/- 11 micromolar) than has that from other members of the grass family (46 +/- 10 micromolar).


Crystal Facet Structure Dependence and Promising Pd-Based Catalytic Materials for Resistance toward Deactivation and Catalytic Performance in Direct Oxidative Esterification.
Designing an effective Pd-based catalytic material with higher stability and catalytic performance for direct oxidative esterification is a great challenge. In this work, a systematic study on the activation mechanism of H2O on the different crystal facets of monometallic Pd, bimetallic Pd-Pb(Bi), and trimetallic Pd-Pb-Bi catalysts was first performed, which showed that the (111) crystal facet of Pd-Pb-Bi had stronger stability of resistance toward deactivation induced by H2O. Further, a detailed direct oxidative esterification mechanism on the screened crystal facet was investigated, where Pd-Pb-Bi catalytic materials showed higher stability and intrinsic catalytic performance for direct oxidation esterification, which was attributed to a dimer Pd-active unit and the synergistic effect of Pb and Bi compared to that of Pd-Pb(Bi) and Pd and also applied to other aldehydes with electron-donating groups producing corresponding esters. Meanwhile, the essential relationship between structures of Pd-based catalytic materials and catalytic performance for direct oxidation esterification was obtained. This work opens up a new simultaneous path for improving the stability of resistance toward deactivation and catalytic performance for direct oxidative esterification of Pd-based catalytic materials, which can be realized by regulating the surface-active unit with dimer Pd adsorbed more O-preadsorbed using Pb and Bi promoters.


Profiling microRNA expression using sensitive cDNA probes and filter arrays.
MicroRNAs (miRNAs) are small noncoding RNAs (approximately 22 nucleotides) that have recently emerged as important regulators of gene expression in both plants and animals. With few exceptions, however, the target genes and the expression levels of most miRNAs are unknown. Here we show that direct random-primed cDNA synthesis on either chemically synthesized small RNAs (21-22 nucleotides) or gel-purified mature miRNAs from human cells can produce specific and sensitive full-length cDNA probes. Using oligonucleotide filter arrays, we demonstrate that the internally labeled cDNA probes are sensitive for detecting differential miRNA expression between untreated and O-tetradecanoylphorbol-13-acetate (TPA)-treated HL60 cells. The present study should facilitate a high-throughput analysis of miRNA expression between samples.


Nanomechanics of biocompatible hollow thin-shell polymer microspheres.
The nanomechanical properties of biocompatible thin-shell hollow polymer microspheres with approximately constant ratio of shell thickness to microsphere diameter were measured by nanocompression tests in aqueous conditions. These microspheres encapsulate an inert gas and are used as ultrasound contrast agents by releasing free microbubbles in the presence of an ultrasound field as a result of free gas leakage from the shell. The tests were performed using an atomic force microscope (AFM) employing the force-distance curve technique. An optical microscope, on which the AFM was mounted, was used to guide the positioning of tipless cantilevers on top of individual microspheres. We performed a systematic study using several cantilevers with spring constants varying from 0.08 to 2.3 N/m on a population of microspheres with diameters from about 2 to 6 microm. The use of several cantilevers with various spring constants allowed a systematic study of the mechanical properties of the microsphere thin shell at different regimes of force and deformation. Using thin-shell mechanics theory for small deformations, the Young's modulus of the thin wall material was estimated and was shown to exhibit a strong size effect: it increased as the shell became thinner. The Young's modulus of thicker microsphere shells converged to the expected value for the macroscopic bulk material. For high applied forces, the force-deformation profiles showed a reversible and/or irreversible nonlinear behavior including "steps" and "jumps" which were attributed to mechanical instabilities such as buckling events.


A prospective randomized comparison of patellar tendon versus semitendinosus and gracilis tendon autografts for anterior cruciate ligament reconstruction.
Seventy patients with patellar tendon or hamstring tendon autografts for single-incision anterior cruciate ligament reconstruction were evaluated at least 2 years after surgery. All reconstructions were performed by the same surgeon, and metal interference screws were used for fixation of all grafts. No significant differences were noted between groups for Lysholm score, reduction in activity, KT-1000 arthrometer findings, quadriceps muscle size, return to sports, or ability to jump and do hard cuts and pivots. Significantly more patients in the patellar tendon group had patellofemoral pain at 6 months after surgery than did the hamstring tendon patients (48% versus 20%), and at last follow-up the incidence of patellofemoral pain was 42% and 20%, respectively. Fourteen patients in the patellar tendon group and seven in the hamstring tendon group had loss of motion (approximately 5 degrees ). Four patients (two in each group) had treatment failures and their results were not included in the clinical examination data. At 2 years' follow-up, 97% of patients with patellar tendon grafts and 100% of patients with hamstring tendon grafts rated their results as good or excellent. We found that hamstring tendon grafts performed similarly to patellar tendon grafts, although fewer patients in the hamstring tendon group had patellofemoral pain and loss of motion.


Structural Analysis of SMYD3 Lysine Methyltransferase for the Development of Competitive and Specific Enzyme Inhibitors.
Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, hepatocellular carcinomas, and breast cell carcinomas support a model in which its aberrant expression modifies established patterns of gene expression, ultimately driving unrestrained proliferation. Herein, we dissect the unique structural features of SMYD3 relative to other SET enzymes, with an emphasis on the implications for selective design of therapeutics for the clinical management of cancer. Further, we illustrate the ability of inhibitors targeting the SET domain of SMYD3 to reduce the viability of colorectal and lung carcinoma cells.


Physical, behavioral, and hormonal changes in the resumption of sexual receptivity during postpartum infertility in female bonobos at Wamba.
The operational sex ratio (OSR) is used as a predictor for the intensity of mating competition. While many factors affect the OSR, there tends to be a high male bias in primate species with long interbirth intervals and non-seasonal breeding, such as hominid apes. However, the OSR of bonobos (Pan paniscus) is lower than that of chimpanzees (Pan troglodytes), which is thought to reduce competitive and aggressive male behaviors. The low OSR of bonobos is considered to result from the early resumption of female sexual receptivity during postpartum infertility and the receptivity that they continue to show until the late stage of pregnancy. In this study, we aimed to examine the early resumption of sexual receptivity by providing quantitative data on the resumption of maximal swelling (MS) in sexual skin and copulation, and changes in urinary estrone conjugate (E1C) concentrations during postpartum infertility in wild bonobos at Wamba in the Luo Scientific Reserve, Democratic Republic of the Congo. An analysis of 9 years of data revealed that females showed the first MS at 225.4 ± 132.7 days after parturition and performed the first copulation at 186.8 ± 137.5 days after parturition, both of which were in the early stage of postpartum infertility. The proportion of days with MS and the frequency of copulation steadily increased subsequently; however, the rate of increase gradually slowed approximately 42-48 months after parturition. There was a significant correlation between the proportion of days with MS and the frequency of copulation in each period for each female. We confirmed that E1C concentrations were significantly higher during the MS phase than during the non-MS phase. Data collected over 15 months on the E1C concentration during MS showed that it increased linearly from the early stage of lactation to the next conception. These results suggest that, although female bonobos do not usually conceive until 49.7 months after parturition, they resume MS and receptivity at a low level of E1C concentration during an early stage of postpartum infertility. This study of female bonobo receptivity and sex hormone changes during the postpartum non-fertile period provides important insights for examining the evolution of low OSR, which has been considered to contribute to peaceful social relationships among bonobos.


[Clinical review of 97 patients with endometrial stromal sarcoma].
To review the survival outcomes in patients with endometrial stromal sarcoma (ESS) in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, and to discuss prognostic factors and the role of post-operative adjuvant radiotherapy and chemotherapy. Hospital records and pathology reports for 97 patients with ESS were reviewed. Among 97 patients, 69 had low-grade ESS (LGESS), 16 had high-grade ESS (HGESS) and 12 had unclear grade. The median age at diagnosis was 44.0 years. The median follow-up time was 62 months (5 - 277 months). Atypical vaginal bleeding (43%) and prolonged and increased menses (36%) were the main symptoms. Totally 2-year and 5-year cumulative survival rates were 93% and 84%, respectively. Cumulative survival curves were significantly different between LGESS and HGESS, and so did cumulative survival curves between stage I - II and stage III - IV (P < 0.05). Totally, 34 patients (37%) had local or distant recurrence. The median time-to-recurrence (TTR) was 27 months. The recurrence rates of the patients with or without preserve of ovary were 89% and 24%, respectively (P = 0.000). The local-control-rates of the patients who received or did not receive post-operative radiotherapy were 81% and 43%, respectively (P = 0.011). The prognosis of HGESS is obviously worse than that of LGESS. The risk of recurrence of patients with preserve of ovary was remarkably higher than that of patients without preserve of ovary. Postoperative radiotherapy could increase the local-control-rates.


Cigarette smoking and ADHD: An examination of prognostically relevant smoking behaviors among adolescents and young adults.
Attention-deficit/hyperactivity disorder (ADHD) is associated with health risks in adolescence which includes the potential for smoking cigarettes, early smoking initiation, and rapid progression to daily smoking. Much less is known, however, about prognostically relevant smoking behaviors among individuals with childhood ADHD. Further research in this area is important for identifying individuals at pronounced risk for nicotine addiction, and for developing effective interventions for this population. This study examined initiation of cigarette smoking, progression to regular smoking, quantity of use, indicators of tobacco dependence, and quit rates among adolescents and young adults with (n = 364) and without (n = 240) childhood ADHD. Individuals with, versus without, ADHD histories were significantly more likely to become daily smokers independent of conduct disorder (CD). They were also more likely to initiate smoking at younger ages and to progress to regular smoking more quickly. There were no significant group differences in cigarettes smoked per day, Fagerström Test of Nicotine Dependence (FTND), or Nicotine Dependence Syndrome Scale (NDSS) scores or in smoking within 30 min of waking. However, smokers with ADHD reported more intense withdrawal and craving during periods of abstinence than non-ADHD smokers. There were no significant group differences in number of quit attempts. Lastly, there were no significant differences among symptom persisters and desisters in daily smoking and amount. Individuals with ADHD histories are at high risk for persistent smoking given their early onset, rapid course, and abstinence characteristics. Smoking cessation programs may need to be adapted or otherwise intensified for those with ADHD. (PsycINFO Database Record


Analysis of the differences in microbial community structures between suspended and sessile microorganisms in rivers based on quinone profile.
In this study, a quinone profiling method was applied to clarify the differences in community structure between suspended and sessile microorganisms in rivers. The compositions of microbial quinone of 6 sites for 4 rivers were analyzed. Ubiquinone (UQ)-8, UQ-10, menaquinone (MK)-7, and plastoquinone (PQ)-9 were observed in all samples of suspended and sessile microorganisms for the sites investigated. The dominant quinone species in suspended microorganisms was ubiquinone, and that in sessile microorganism was photosynthetic quinones (namely PQ-9 and vitamin K1). This indicated that aerobic bacteria were abundant in the suspended microorganisms, and photosynthetic microorganisms such as micro-algae and cyanobacteria dominated in the sessile microorganisms. The quinone concentration in the river waters tested, which reflects the concentration of suspended microorganisms, ranged from 0.045 to 1.813 nmol/L. The microbial diversities of suspended and sessile microorganisms calculated based on the composition of all quinones were in the range from 3.4 to 7.5, which was lower than those for activated sludge and soils. Moreover, the diversity of heterotrophic bacteria for sessile microorganisms in the rivers was higher than that for the suspended microorganisms.


Degradation of hydroxypropyl guar gum at wide pH range by a heterogeneous Fenton-like process using bentonite-supported Cu(0).
To seek for efficient Fenton-like oxidation processing for treatment of waste fracturing fluid containing hydroxypropyl guar gum (HPGG), in heterogeneous reaction, five bentonite-supported zero-valent metal catalysts were prepared by liquid-phase reduction. The results showed that the bentonite-supported zero-valent copper exhibited best catalytic performance, attributed to the high dispersion of active sites of zero-valent copper. The effects of the most relevant operating factors (H2O2 concentration, catalyst dosage, temperature and pH) were evaluated in detail. Moreover, the chemical oxygen demand removal rate of HPGG can achieve 76% when the reaction time was selected at 45 min under optimal experimental conditions. The stability evaluation showed that the catalytic performance was almost unaffected after the catalyst was recycled and used once more showing the good stability of the bentonite-supported zero-valent copper in the application process.


Comparative Evaluation of McGrath MAC, Truview Video Laryngoscopes and Macintosh Laryngoscope for Endotracheal Intubation in Patients Undergoing Surgery under General Anaesthesia.
Videolaryngoscopy is a newly developed technique to improve tracheal intubation success. It was made to bypass the need of directly visualising the glottic inlet. These devices are advantageous as there is no need of aligning the laryngeal, pharyngeal and oral axes for a clear view, thus making intubation easier and faster. Primary objective of the study was to determine the duration of laryngoscopy and intubation and Cormack - Lehane grading when intubating with McGrath MAC, Truview video laryngoscope and Macintosh laryngoscope. Secondary objectives of the study were to determine the number of attempts and optimization manouveres required to intubate. This study was conducted on total of 120 patients in age 20-70 years, either sex, with American Society of Anaesthesiologists physical status classes I or II scheduled for elective surgery under general anaesthesia. They were randomly assigned equally to group 1, 2 and 3 (n = 40) to be intubated by Mcgrath MAC video laryngoscope, Truview video laryngoscope and Macintosh laryngoscope respectively. Parameters recorded were duration of laryngoscopy and intubation, Cormack Lahane grading, ease of intubation, number of attempts and optimisation manouveres required for intubation. Comparison of mean value among the three groups was done using student t test and percentage comparison was done using chi square test. To compare more than two variables ANOVA test was used. The P values of less than 0.05 was considered statistically significant. Duration of laryngoscopy was significantly less in McGrath MAC group when compared to Truview group (P = 0.02) and to Macintosh group (P < 0.001) and the duration of intubation was comparable among all three study groups (P > 0.05). The difference in Cormack - Lehane grading was not significant between McGgrath MAC and Trueview (P = 0.71) but was significant between McGrath MAC and Macintosh (P = 0.002) and Trueview and Macintosh (P = 0.002). Ease of intubation was better in McGrath MAC and Truview groups compared to Macintosh group (P < 0.05). Intubation was successful in the first attempt in 39 (97.50%) patients in McGrath MAC group, 40 (100%) patients in Truview group and 35 (87.50%) patients in Macintosh group. McGrath MAC and Truview groups performed better with respect to optimization manoeuvres compared to Macintosh group (P < 0.05). Trauma was observed in 2 (5%) patients in Truview group and 5 (12.50%) patients in Macintosh group. In McGrath MAC group, no patient underwent any trauma. Although duration of laryngoscopy was significantly shorter in McGrath as compared to Truview video laryngoscope and Macintosh laryngoscope but the duration of intubation was comparable between the three groups. Both these video laryngoscopes performed significantly better than Macintosh laryngoscope with respect to laryngoscopic view, requirement of optimization manoeuvre and need for second attempt for intubation.


[A successfully treated case of aspiration pneumonia with adult respiratory distress syndrome and shock].
Right hip replacement was scheduled for a 74-year-old man who was treated with morphine for cancer pain. As the patient developed dyspnea and hypoxia after anesthesia, he was intubated and kept under mechanical ventilation. A diagnosis of aspiration pneumonia with adult respiratory distress syndrome was made based on the detection of gall obtained from the endotracheal tube. A chest X-ray showed pulmonary edema. He was treated with positive pressure ventilation and inotropic support. As he developed severe shock 10 hours after the intubation, he was treated with 20 mg.kg-1 of methylprednisolone for 3 days. The steroid therapy was successful and he was extubated on the 6th postoperative day and was discharged from the ICU on the 7th postoperative day. High-dose pulse methylprednisolone therapy resulted in a remarkable clinical improvement. Corticosteroids rescue treatment is effective for such a severe case of aspiration pneumonia with shock when the treatment is done in the early phase of the pneumonia.


Two exercise schemes in postoperative breast cancer: comparison of effects on shoulder movement and lymphatic disturbance.
We attempted to determine the best method of performing the exercises in rehabilitation after breast cancer surgery and their influence on postoperative complications. Currently, there are no guidelines for these exercises. The scope of this study was to evaluate the effect of two schemes of physiotherapy exercises (directed or free) on shoulder function and lymphatic disturbance in postoperative rehabilitation. Sixty women who underwent a modified radical mastectomy or quadrantectomy with axillary dissection were randomized into two groups. The physiotherapy technique used was kinesiotherapy. The directed group performed physiotherapy following a regimen of 19 exercises. The free group performed the exercises following the biomechanical physiological movements of the shoulder without a previously defined sequence or number of repetitions. The averages of the flexion, abduction and external rotational movements of the shoulder showed better recovery with statistical significance in the directed group compared to the free group. There was no significant difference between the groups in lymphatic disturbance. At the end of 42 days of follow-up, the movements of flexion, extension, abduction and external rotation of the shoulder were better rehabilitated in the directed group. The two schemes of exercises were not different with regard to lymphatic disturbance.


Quantifying Protein Disorder through Measures of Excess Conformational Entropy.
Intrinsically disordered proteins (IDPs) and proteins with a large degree of disorder are abundant in the proteomes of eukaryotes and viruses, and play a vital role in cellular homeostasis and disease. One fundamental question that has been raised on IDPs is the process by which they offset the entropic penalty involved in transitioning from a heterogeneous ensemble of conformations to a much smaller collection of binding-competent states. However, this has been a difficult problem to address, as the effective entropic cost of fixing residues in a folded-like conformation from disordered amino acid neighborhoods is itself not known. Moreover, there are several examples where the sequence complexity of disordered regions is as high as well-folded regions. Disorder in such cases therefore arises from excess conformational entropy determined entirely by correlated sequence effects, an entropic code that is yet to be identified. Here, we explore these issues by exploiting the order-disorder transitions of a helix in Pbx-Homeodomain together with a dual entropy statistical mechanical model to estimate the magnitude and sign of the excess conformational entropy of residues in disordered regions. We find that a mere 2.1-fold increase in the number of allowed conformations per residue (∼0.7kBT favoring the unfolded state) relative to a well-folded sequence, or ∼2(N) additional conformations for a N-residue sequence, is sufficient to promote disorder under physiological conditions. We show that this estimate is quite robust and helps in rationalizing the thermodynamic signatures of disordered regions in important regulatory proteins, modeling the conformational folding-binding landscapes of IDPs, quantifying the stability effects characteristic of disordered protein loops and their subtle roles in determining the partitioning of folding flux in ordered domains. In effect, the dual entropy model we propose provides a statistical thermodynamic basis for the relative conformational propensities of amino acids in folded and disordered environments in proteins. Our work thus lays the foundation for understanding and quantifying protein disorder through measures of excess conformational entropy.


Influence of safety motivation and climate on safety behaviour and outcomes: evidence from the Saudi Arabian construction industry.
Over the last three decades, safety literature has focused on safety climate and its role in forecasting injuries and accidents. However, research findings regarding the relationships between safety climate and other key outcome constructs are somewhat inconsistent. Recent safety climate literature suggests that examining the role of safety motivation may help provide a better explanation of such relationships. The research presented in this article aimed to empirically analyse the relationships among safety motivation, safety climate, safety behaviour and safety outcomes within the context of the Saudi Arabian construction industry. A conceptual model was developed to examine the relationships among four main constructs: safety motivation, safety climate, safety behaviour and safety outcomes. Based on the survey data collected in Saudi Arabia from site engineers and project managers (n = 295), statistical analyses were carried out, including confirmatory and exploratory factor analysis, and structural equation modelling to assess the model and test the hypotheses. The main results indicated that safety motivation could positively influence safety behaviour through safety climate, which plays a mediating role for this mechanism. The results also confirmed that safety behaviour could predict safety outcomes within the context of the Saudi Arabian construction industry.


Addressing substance use in primary care.
Problematic use of alcohol, tobacco, and other drugs, including prescription medications, contributes to increased risk for injury, illness, suffering, and premature death across the lifespan. Nurse practitioners can positively impact the health of patients, their families, and communities by addressing substance use and related disorders in primary care settings.


Functional properties of developing rat Leydig cells after treatment with ethylene dimethanesulphonate (EDS).
The development of a new population of Leydig cells after specific elimination of existing Leydig cells in mature rats by ethylene dimethanesulphonate (EDS) was characterized by investigating the testicular activities of 5 alpha-reductase and non-specific esterase, the serum concentrations of 3 alpha-androstanediol and testosterone and the Leydig cell morphology. Plasma concentrations of both androgens were strongly reduced up to 15 days after administration of EDS. Thereafter, in contrast to the gradual and continuous increase of serum testosterone values, the changes in serum 3 alpha-androstanediol were transient, with the highest level on Day 35. The temporal pattern of testicular 5 alpha-reductase activity was almost similar to that of serum 3 alpha-androstanediol. The testicular esterase activity increased gradually from Day 25 until Day 76. The temporal changes in steroid concentrations and enzyme activities after EDS administration indicate that the development of the Leydig cells in EDS-treated rats occurs in a fashion similar to that in pubertal rats. However, the numerous lipid droplets and large nuclei in these Leydig cells indicate that these cells may also be classified as fetal cells. It is concluded that, after treatment with EDS, fetal and pubertal characteristics are present in Leydig cells. It is, however, unknown whether both characteristics are present in one or in two distinct cell populations.


Vectors: recognising the challenge and reducing neglect.
Vector control is essential for the prevention and reduction of malaria transmission and is increasingly recognised as a key element of several neglected tropical disease (NTD) elimination programmes. Very few vector control interventions have a strong evidence base for their public health impact, and those that do are insecticide-based and threatened by resistance. The pipeline of new interventions and new insecticides is being filled and several are undergoing randomised controlled trials. If these are subsequently to be used sustainably, interventions will need to be combined. The major challenge will be to generate the evidence base and funding to achieve this sustainable combination at the country level. Unless this is done, the selection pressure for resistance to the new generation of vector control tools is likely to rapidly reduce our ability to control insect vectors in the foreseeable future.


Physiological principles of Starling-like control of rotary ventricular assist devices.
Introduction: This review explores the Starling-like physiological control method (SLC) for rotary ventricular assist devices (VADs) for severe heart failure. The SLC, based on mathematical models of the circulation, has two functions modeling each ventricle. The first function controls the output of the VAD to the arterial pool according to Starling's law, while the second function accounts for how the blood returns to the heart from the veins. The article aims to expose clinicians to SLC in an accessible and clinically relevant discussion. Areas Covered: The article explores the physiology underlying the controller, its development and how that physiology can be adapted to SLC. Examples of controller performance are demonstrated and discussed using a benchtop model of the cardiovascular system. A discussion of the limitations and criticisms of SLC is presented, followed by a future outlook on the clinical adoption of SLC. Expert Opinion: Due to its simplicity and emulation of the natural cardiac autoregulation, SLC is the superior physiological control method for rotary VADs. However, current technical and regulatory challenges prevent the clinical translation of SLC of VADs. Further technical and regulatory development will enable the clinical translation of SLCs of VADs in the coming years.


The microbial metabolome in metabolic-associated fatty liver disease.
Metabolism-associated fatty liver disease (MAFLD) is defined as the presence of excess fat in the liver in the absence of excess alcohol consumption and metabolic dysfunction. It has also been described as the hepatic manifestation of metabolic syndrome. The incidence of MAFLD has been reported to be 43-60% in diabetics, ~90% in patients with hyperlipidemia, and 91% in morbidly obese patients. Risk factors that have been associated with the development of MAFLD include male gender, increasing age, obesity, insulin resistance, diabetes, and hyperlipidemia. All of these risk factors have been linked to alterations of the gut microbiota, that is, gut dysbiosis. MAFLD can progress to non-alcoholic steatohepatitis with the presence of inflammation and ballooning, which can deteriorate into cirrhosis, MAFLD-related hepatocellular carcinoma, and liver failure. In this review, we will be focused on the role of the gut microbial metabolome in the development, progression, and potential treatment of MAFLD.


Effects of kinesiotape on pain, range of motion, and functional status in patients with osteoarthritis: a randomized controlled trial.
This study aimed to determine the effects of kinesiotape (KT) on pain, range of motion, and functional status in patients with osteoarthritis of the knee. In this randomized controlled trial, patients with knee osteoarthritis, based on American College of Rheumatology criteria, and Kellgren-Lawrence grade 2 or 3 criteria were selected. Visual analogue scale and active range of motion were the primary outcome measures. Timed Up and Go test and 6-min walk test, were the secondary outcome measures. Evaluation was performed at baseline (T0), after 1 hr (T1), and after 72 hr (T2). We recruited 27 patients with osteoarthritis (age, 57.33±8.72 years; 63% female; body mass index, 29.7±4.3 kg/m2) who were randomly assigned into KT or sham-KT groups. There was a significant group by time interaction for the visual analogue scale (P< 0.001, η 2=0.593), active range of motion (flexion) (P<0.001, η 2=0.492), active range of motion (extension) (P<0.001, η 2=0.351), 6-min walk test (P<0.001, η 2=0.568), and Timed Up and Go test (P=0.026, η 2=0.136). Between-group comparisons revealed significant differences between KT and sham-KT in visual analogue scale and Timed Up and Go test in T1 and T2 assessments, with changes in knee flexion (P<0.002) and extension active range of motion (P<0.010) and 6-min walk test (P<0.044) at 72-hr posttreatment. This study showed that, 1 hr of KT is an effective treatment for decreasing pain and improving active range of motion and physical function at a 72-hr follow-up in patients with osteoarthritis.


Application of machine learning in understanding plant virus pathogenesis: trends and perspectives on emergence, diagnosis, host-virus interplay and management.
Inclusion of high throughput technologies in the field of biology has generated massive amounts of data in the recent years. Now, transforming these huge volumes of data into knowledge is the primary challenge in computational biology. The traditional methods of data analysis have failed to carry out the task. Hence, researchers are turning to machine learning based approaches for the analysis of high-dimensional big data. In machine learning, once a model is trained with a training dataset, it can be applied on a testing dataset which is independent. In current times, deep learning algorithms further promote the application of machine learning in several field of biology including plant virology. Plant viruses have emerged as one of the principal global threats to food security due to their devastating impact on crops and vegetables. The emergence of new viral strains and species help viruses to evade the concurrent preventive methods. According to a survey conducted in 2014, plant viruses are anticipated to cause a global yield loss of more than thirty billion USD per year. In order to design effective, durable and broad-spectrum management protocols, it is very important to understand the mechanistic details of viral pathogenesis. The application of machine learning enables precise diagnosis of plant viral diseases at an early stage. Furthermore, the development of several machine learning-guided bioinformatics platforms has primed plant virologists to understand the host-virus interplay better. In addition, machine learning has tremendous potential in deciphering the pattern of plant virus evolution and emergence as well as in developing viable control options. Considering a significant progress in the application of machine learning in understanding plant virology, this review highlights an introductory note on machine learning and comprehensively discusses the trends and prospects of machine learning in the diagnosis of viral diseases, understanding host-virus interplay and emergence of plant viruses.


TBAI-Catalyzed Oxidative Coupling of Benzyl Ketones to Synthesize 2,3-Diaryl-1,4-Diketones in Water.
An efficient and green route of C-C bond formation was disclosed to construct 2,3-diaryl-1,4-diketones from α-methylene ketones by the catalysis of tetrabutylammonium iodide (TBAI) with tert-butyl hydroperoxide (TBHP) as an oxidant in water. This reaction affords the desired products in good to excellent yields from readily available materials, with a broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, tetrasubstituted furan and pyrrole were smoothly constructed from α-methylene ketones in one pot with 96 and 90% yields, respectively.


Diagnostic value of 123I-phenylpentadecanoic acid (IPPA) metabolic and thallium 201 perfusion imaging in stable coronary artery disease.
The diagnostic value of 123I-phenylpentadecanoic acid (IPPA) metabolic cardiac imaging was studied in a group (n = 29) of patients with angiographically confirmed CAD using single photon emission computed tomography (SPECT). A symptom-limited exercise test was first done with IPPA, and 2 days later with thallium. Medications were not withheld during testing. Fourteen healthy control subjects participated in parallel IPPA and 15 in thallium tests. Data acquisition and output were comparable in the two imaging modalities. By testing various relatively simple criteria for abnormality we found that the semiquantitative interpretation was more accurate than the visual readings. The best compromise of accuracy with the scored criteria consisted of a sensitivity of 86% and a specificity of 86%, obtained with IPPA polar tomograms (mild exercise defect) and a sensitivity of 86% and a specificity of 80% obtained with thallium (regionally decreased washout). With visual interpretation alone, a sensitivity of 83% and a specificity of 71% was detected with IPPA (mild exercise defect) and 72% and 73%, respectively, with thallium (partial reversibility). The sensitivity of the exercise ECG alone was 62%. The results of this study imply that IPPA imaging could be a rational, uncomplicated clinical method for non-invasive diagnosis of CAD. The diagnostic ability of IPPA is at least as good as that of thallium, and it is possible to use them in succession.


Prevalence and Antibiotic Susceptibility Patterns of Extended-Spectrum ß-Lactamase and Metallo-ß-Lactamase-Producing Uropathogenic Escherichia coli Isolates.
Healthcare professionals worldwide have expressed concern over infections by extended-spectrum ß-lactamase (ESBL) and metallo-ß-lactamase (MBL)-producing bacteria. We evaluated the prevalence of ESBL- and MBL-producing Escherichia coli (E. coli) isolated from community-acquired urinary tract infections (UTIs) and their antibiotic-resistance profiles at 3 private laboratories in Tehran, Iran. E. coli isolates were mostly susceptible to meropenem (90.4%) and imipenem (90.0%), followed by amikacin (89.0%) and gentamicin (84.7%). Moreover, we detected that, of the E. coli isolates, 67 (22.3%) were ESBL producers and 21 (7.0%) of E. coli isolates were MBL positive via the imipenem-ethylenediaminetetraacetic acid (EDTA) combined disc test. This report is the first, to our knowledge, on the prevalence of MBL-producing uropathogenic E. coli (UPEC) strains in Iran. The antibiotic resistance of E. coli isolates revealed that 122 (40.7%) were multidrug resistant. The high number of antibiotic-resistant and ß-lactamase-producing UPEC strains necessitates further attention and consideration, particularly MBL-producing strains.


Biomonitoring for Exposure Assessment to Styrene in the Fibreglass Reinforced Plastic Industry: Determinants and Interferents.
Fifty-eight workers exposed to styrene were monitored in four fibreglass reinforced plastic industries of Central Italy. The aim of the study was to explore the factors that can influence the levels of styrene exposure biomarkers of the workers and the aspects that might interfere with the exposure assessment measures, such as the co-exposure to acetone. Personal monitoring of professional exposure to airborne styrene and acetone was carried out by Radiello samplers and GC/MS analysis. Biological monitoring was performed by the determination of urinary metabolites, mandelic (MA), and phenylglyoxylic (PGA) acids with HPLC/MS/MS and unmetabolized styrene in saliva and venous blood by HS/GC/MS. The median values of the four sites ranged between 24.1 to 94.0mg m(-3) and 7.3 to 331.1mg g(-1) creatinine for airborne styrene and MA + PGA, respectively. A good linear correlation was found between styrene in air and its urinary metabolites (r = 0.854). The median value for airborne styrene was found to exceed the (Threshold Limit Value - Time Weighted Average) of 85 mg m(-3) in one site for all the workers and in two if only moulders are considered. The multiple linear regression model showed that the determinants of urinary MA + PGA excretion were the type of process, workers' tasks, level of acetone co-exposure, and the use of respiratory protection devices. Data show that the simultaneous exposure to acetone modify the styrene metabolism with a reduction in the levels of (MA + PGA) excreted. A significant linear log-correlation was found between salivary levels of styrene and blood concentration (r = 0.746) sampled at the same t x time.