[New infectious risks].
New infectious risks have been identified or better elucidated in the last few years. The concept of infectious risks implies: a receptive host; or more or less pathogenic agent, inducing pathologic phenomena with variable facility, depending the receptivity of the host; and individual or community environmental factors (risk of accidental and massive contact with a pathogenic agent). These new risks are linked to: 1. the appearance of new or newly identified pathogenic agents, and the periodic changes in the pathogenic strength of some microorganisms, modifying the epidemiology of some infections; 2. changes in host receptivity (immunodepression, either acquired or linked to aggressive therapy which leads to prolonged survival of receptive patients); 3. environmental modifications (spread of resistant pathogenic bacteria, for example, presently the tuberculosis bacillus; declining socioeconomic conditions; reduced efficacy of community measures for prevention); 4. exposure to new risks linked to progress in diagnostic and therapeutic techniques (invasiveness of medical treatments, new treatment techniques, transplantations, implantation of foreign materials, transfusions). These phenomena illustrate the constant change in infectious risks and the need for a multidisciplinary approach to the problem and its effects.


Phases of transition in cognitive development: evidence from the domain of spatial representation.
Data on changes in children's map drawing ability are used to examine 3 hypotheses concerning the relationship of level mixture to developmental change as proposed by Damon in a recent study of social reasoning: (1) that high total mixture precedes change, (2) that low total mixture precedes change, and (3) that high positive mixture (i.e., that at stages above the mode) precedes change. Further predictions are derived from our 6-phase model of transition; these are compared and contrasted with conclusions reached by Damon. Using Damon's approach, we replicate his finding that high positive mixture precedes model advance. More detailed analyses of 2 separate groups as suggested by the transitions model, however, show that all 3 types of mixture precede developmental change, albeit different types of change within each group.


Longitudinal myocardial blood flow gradient and CAD detection.
Conventional myocardial perfusion scintigraphy with SPECT/CT or with PET/CT has been established as pivotal clinical imaging modality for the identification of hemodynamically obstructive coronary artery disease (CAD) and risk stratification of patients with suspected or known CAD. While the assessment of the relative distribution of radiotracer uptake in the left-ventricular (LV) myocardium during vasomotor stress identifies the "culprit" or most severe CAD lesion in multivessel disease, flow-limiting effects of remaining but less severe epicardial lesions may be missed. This limitation principally may be overcome by the possibility of PET/CT with radiotracer-kinetic modeling to concurrently assess left-ventricular (LV) myocardial blood flow (MBF) in ml/g/min at rest and during vasomotor stress and the resulting myocardial flow reserve (MFR). While a stress-induced regional reduction in radiotracer uptake or perfusion identifies the most advanced epicardial lesion, flow-limiting effects of the other epicardial lesions may principally be identified by regional reductions in MFR. Conversely, reductions in MFR in CAD may be appreciated as suboptimal as they reflect not only the consequences of flow-limiting effects of epicardial stenosis but also of microvascular dysfunction. The relatively low specificity of a reduced therefore MFR may hamper a clear identification of the downstream hemodynamic effects of an epicardial lesion on hyperemic coronary flow increases. In this scenario, there is increasing evidence that the PET assessment of an abnormal decrease in MBF from the base to the apex of the LV during hyperemic flows, a so-called longitudinal flow gradient, is primarily related to fluid dynamic consequences of CAD-induced diffuse luminal and/or focal narrowing of the epicardial artery. The combined evaluation of the MFR and corresponding longitudinal MBF gradient could emerge as new a novel analytic concept to further optimize the identification and characterization of hemodynamic CAD burden in multivessel disease, which, however, warrants further clinical validation.


The Caenorhabditis elegans pvl-5 gene protects hypodermal cells from ced-3-dependent, ced-4-independent cell death.
Programmed cell death (PCD) is regulated by multiple evolutionarily conserved mechanisms to ensure the survival of the cell. Here we describe pvl-5, a gene that likely regulates PCD in Caenorhabditis elegans. In wild-type hermaphrodites at the L2 stage there are 11 Pn.p hypodermal cells in the ventral midline arrayed along the anterior-posterior axis and 6 of these cells become the vulval precursor cells. In pvl-5(ga87) animals there are fewer Pn.p cells (average of 7.0) present at this time. Lineage analysis reveals that the missing Pn.p cells die around the time of the L1 molt in a manner that often resembles the programmed cell deaths that occur normally in C. elegans development. This Pn.p cell death is suppressed by mutations in the caspase gene ced-3 and in the bcl-2 homolog ced-9, suggesting that the Pn.p cells are dying by PCD in pvl-5 mutants. Surprisingly, the Pn.p cell death is not suppressed by loss of ced-4 function. ced-4 (Apaf-1) is required for all previously known apoptotic cell deaths in C. elegans. This suggests that loss of pvl-5 function leads to the activation of a ced-3-dependent, ced-4-independent form of PCD and that pvl-5 may normally function to protect cells from inappropriate activation of the apoptotic pathway.


'Weak' research undermines profession.
The contribution of nursing is being underestimated because of 'weak and small scale' research, a leading workforce expert has warned.


Comparison of drug-eluting balloon angioplasty with self-expanding interwoven nitinol stent deployment in patients with complex femoropopliteal lesions.
Objective The aim of this study was to compare the drug-eluting balloon with self-expanding interwoven nitinol stent deployment in patients with complex femoropopliteal lesions. Methods We retrospectively identified patients at our clinic with complex femoropopliteal artery lesions treated either with self-expanding interwoven nitinol stent or drug-eluting balloon. All patients had ankle-brachial index measured before and after the intervention, and regular clinical follow-up with Doppler ultrasonography was performed at six months and one year. Patients underwent peripheral angiography if needed. Results From April 2012 to July 2015, 107 patients with complex femoropopliteal lesions treated with using self-expanding interwoven nitinol stent ( N = 49, mean length 143.5 mm, mean follow-up of 14.1 ± 3.7 months) or drug-eluting balloon ( N = 58, mean length 140.6 mm, mean follow-up of 13.8 ± 4.1 months). The technical success rate was 100% in Supera® and 96.6% in drug-eluting balloon group. There were seven restenosis in self-expanding interwoven nitinol stent (SUS) group (84.8% patency) and 11 restenosis in drug-eluting balloon group (79.2% patency). A significant increase in the ankle-brachial index in both groups after intervention demonstrated a hemodynamic success (SUS group 0.45 ± 0.06, drug-eluting balloon group 0.43 ± 0.07). The mean Rutherford Becker Class significantly decreased in both groups after a follow-up of 12 months (SUS group 0.70 ± 0.73, drug-eluting balloon group 0.74 ± 0.75). Conclusion Deploying drug-eluting balloon or self-expanding interwoven nitinol stent in patients with complex femoropopliteal lesions are both safe and effective with high patency rates with no statistical difference for one-year primary patency rates between them.


Rhodamine B derivative-functionalized upconversion nanoparticles for FRET-based Fe(3+)-sensing.
A novel fluorescence resonance energy transfer (FRET)-based probe, γ-cyclodextrin modified oleic acid-NaYF4:Yb, Ho upconversion nanoparticles functionalized with a rhodamine B derivative (RBD), has been achieved for Fe(3+)-sensing in aqueous solution with high sensitivity and selectivity.


Fabrication of Swellable Organic-Inorganic Hybrid Polymers for CO2-Assisted Hydration of Propylene Epoxide.
Swelling is a very common phenomenon in organic substances. However, the swelling behaviors of inorganic substances had rarely been reported. In this study, a new type of swellable organic-inorganic hybrid polymer (PIL@CHT) was designed and successfully synthesized through free-radical copolymerization of polymerizable phosphonium ionic liquid monomer and vinyl-functionalized hydrotalcite (CHT). The swelling behaviors of PIL@CHT in various solvents with a wide range of Hansen solubility parameters (δT) were investigated, and PIL@CHT exhibited excellent swellable capacity in the solvents with δT > 24.4 MPa1/2. The swollen state of the hybrid PIL@CHT in water presented a network structure with a diameter of approximately 8-12 μm, and CHT particles were well dispersed to the channel of PIL. PIL@CHT was applied to catalyze the CO2-assisted hydration of propylene oxide (PO), in which a cascade reaction including the cycloaddition of CO2 and PO and the subsequent hydrolysis of propylene carbonate (PC) occurred. PIL@CHT, combining the active sites of PIL and CHT, synergistically catalyzed this cascade reaction and achieved a high yield (93.0%) and selectivity (98.2%) of 1,2-propanediol (1,2-MPG) under a low H2O/PO ratio of 1.5/1. Moreover, the catalyst could be recycled seven times without any significant loss of catalytic activities and had good substrate generality.


[Pharmacotherapy of panic disorder].
The concept of Panic Disorders has itself been developed on the strength of therapeutic effects of drug treatments and it is therefore not surprising that psychotropic medications are currently the main therapeutic tool for this condition. Their use may be indicated in two differing circumstances, as treatment for Panic Attack itself or as a long-term treatment for what is properly called Panic Disorder. The latter scenario is that which has been most actively studied and represents the more original side of the question. Treatment of acute Panic Attack involves administration of sedative anxiolytics, principally benzodiazepines (BZD). Long-term treatment aiming to prevent repeated attacks is the core strategy for treatment for Panic Disorder. For the past fifteen years, a large number of research projects have shown the elective anti-panic efficacy of a number of drugs, principally antidepressants and anxiolytics. The response profile to anti-depressant treatment is characterized by a lag time which is sometimes longer than that observed when they are used solely as antidepressants; frequently they are also less well tolerated which necessitates a very gradual step-up in dosage. The "classic" MAOI (non-selective and irreversible) have a proven anti-panic effect. Selective serotonin reuptake inhibitor (SSRI) anti-depressants are currently drugs of choice in the treatment of Panic Disorder. Although the anti-panic effect appears to be common to all the various SSRI drugs available, and directly attributable to their mechanism of action, not all of them however have undergone controlled studies. In France, paroxetine is the first anti-depressant in this group to obtain a marketing authorization for this particular indication. The advantages of the SSRI drugs are principally related to their limited adverse effects and lack of toxicity, thereby making them particularly straightforward to use. Benzodiazepines (BZD) are the second group of psychotropic medications which have been shown to be effective in the treatment of Panic Disorder. The major disadvantage of the BZD for this indication is chiefly related to the major risk of promoting a dependency state with the corresponding appearance of a withdrawal syndrome when treatment is stopped. This risk constitutes a major stumbling block to the use of BZD as a first-line treatment for Panic Disorder. Various other drugs have been evaluated in the treatment of Panic Disorder with varying success. The current anti-panic pharmacopoeia therefore appears to be relatively well stocked. In this context, antidepressants-especially the SSRI drugs-are the first-line treatment of choice for Panic Disorders. In all cases, it appears useful to integrate pharmacological treatment within an overall management plan for the patient with Panic Disorder, especially if it is hoped to maintain therapeutic benefit long-term.


[Clinical significance of intracranial hemorrhage caused by cerebral arteriovenous malformations: with special reference to intraventricular hemorrhage].
Forty-two cases with intracranial hemorrhage caused by cerebral arteriovenous malformation (AVM), which was diagnosed by CT scan, were reviewed with regard to the clinical significance of intracranial hemorrhage, especially intraventricular hemorrhage (IVH). Twenty-one patients were defined as poor risk cases whose level of consciousness at admission was 100 to 300 according to the Japan Coma Scale, whereas the remaining 21 patients were defined as good risk cases. Surgical excision of AVM was undertaken in 35 out of the 42 cases. Urgent surgical removal of intracerebral hematoma and AVM within 24 hours following onset was undertaken in 11 cases. In 14 patients, urgent continuous ventricular drainage was carried out. The effects of the following factors on the level of consciousness at admission, and on the result of AVM treatment were investigated to clarify the clinical significance of intracranial hemorrhage; 1) cast formation of 3rd and/or 4th ventricle, 2) volume of intraventricular hematoma, 3) accompanying intracerebral hematoma and 4) acute hydrocephalus. It was confirmed that all these factors significantly contributed to the development of serious disturbance of consciousness in the acute stage following intracranial hemorrhage. For good risk cases, the rate of patients who showed a good recovery or only moderate disability according to the Glasgow Outcome Scale reached 91%, whereas for poor risk cases, it was only 43%. The presence of large intracerebral hematomas of more than 4 cm in diameter accompanied with IVH was significantly correlated with the result of AVM treatment. The presence or absence of cast formation of 3rd and/or 4th ventricle, volume of intraventricular hematoma and acute hydrocephalus were not significantly related to the result of AVM treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Subclinical ketosis on dairy cows in transition period in farms with contrasting butyric acid contents in silages.
This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).


Monograph on "Lithoglyphopsis" aperta, the snail host of Mekong River schistosomiasis.
We discuss the morphology, histology, ecology, distribution, systematics, and evolutionary relationships of "Lithoglyphopsis" aperta Temcharoen, the snail host of Mekong River Schistosoma sp., and part of a vast, complex, endemic hydrobid fauna consisting of 11 genera and over 80 species. "L" aperta is a member of the Hydrobiidae (as broadly outlined by Fretter & Graham, 1962), subfamily Triculinae (as defined by Davis, 1968b). "L" aperta cannot be assigned to Ltihoglyphopsis because its shell and radula differ from those of the type-species, L. modesta (Gredler) from China, and because L. modesta is apparently more closely allied to other Mekong River genera in these traits. The female reproductive system of "L." aperta is similar to that of Tricula burchi Davis, a species from NW Thailand outside the Mekong River drainage. It is not possible to assign aperta to a named genus until the morphologies of numerous other hydrobiid taxa in the Mekong River are unknown. "L." aperta is typically hydrobiid in grade of morphological organization, in the nervous digestive, ctenidial and male reproductive systems. Differences from other hydrobiid taxa are in the female reproductive system and micromorphological features of the digestive tract. "L." aperta and species of Tricula from Thailand have a female reproduction system where sperm enter at the posterior end of the mantle cavity and travel to the bursa copulatrix via a spermathecal duct. These and related traits are the basis for the subfamily Triculinae. Hydrobiid taxa from Europe (Hydrobiinae s.s.) belong in a different phyletic line, where sperm enter the female reproductive system at the anterior end of the mantle cavity and travel via a ciliated groove in the palial oviduct to the bursa copulatrix. "L." aperta, as well as taxa of the Pomatiopsinae (e.g. Oncomelania, Pomatiopsis), differ from most known mesogastropods in lacking a hypobranchial gland. "L." aperta, other triculines, pomatiopsines and hydrobiines, as well as taxa studied in the Bithyniidae, Truncatellidae and Assimineidae differ from other mesogastropods, e.g. Viviparidae, Pleuroceridae, Littorinidae, etc., in that the salivary glands are dorsal to the nerve ring i.e. do not pass through the nerve ring. "L." aperta lives on solid substrata, particularly wood, shells and leaves in the Mekong River from Khemarat, Thailand, to the Cambodian border, 200 river miles downstream. The range probably extends another 100 river miles downstream to Kratie, Cambodia. It is an "r"-selected species by having a high density-independent mortality and using much of its resources for reproduction. The species is a colonizer in a river with severe annual floods. Females live less than 12 months; they apparently lay eggs in late January or February and die. In early March neither adults nor young can be collected. By mid or late March young suddenly flourish. The new generation does not mature until late May or June, after the beginning of the rainy season...


SILAC Based Proteomic Characterization of Exosomes from HIV-1 Infected Cells.
Proteomics is the large-scale analysis of proteins. Proteomic techniques, such as liquid chromatography tandem mass spectroscopy (LC-MS/MS), can characterize thousands of proteins at a time. These powerful techniques allow us to have a systemic understanding of cellular changes, especially when cells are subjected to various stimuli, such as infections, stresses, and specific test conditions. Even with recent developments, analyzing the exosomal proteome is time-consuming and often involves complex methodologies. In addition, the resultant large dataset often needs robust and streamlined analysis in order for researchers to perform further downstream studies. Here, we describe a SILAC-based protocol for characterizing the exosomal proteome when cells are infected with HIV-1. The method is based on simple isotope labeling, isolation of exosomes from differentially labeled cells, and mass spectrometry analysis. This is followed by detailed data mining and bioinformatics analysis of the proteomic hits. The resultant datasets and candidates are easy to understand and often offer a wealth of information that is useful for downstream analysis. This protocol is applicable to other subcellular compartments and a wide range of test conditions.


C1 Esterase Inhibitor Activity Is Reduced in the Acute Phase Following Burn Injury: A Prospective Observational Study.
Hereditary angioedema has been attributed to an inherited deficiency of C1 esterase inhibitor that increases vascular permeability. The role of C1 esterase inhibitor in burn patients has not been described previously. In this study, we attempted to identify the relationship between serial changes of C1 esterase inhibitor activity and the clinical course in major burn patients. This study was a single-center, prospective, observational study. C1 esterase inhibitor activity values were serially examined in major burn patients admitted into the burn center from April 2014 to December 2016. Inclusion criteria were age ≥16 years old and %TBSA burned ≥20%. This study included 38 patients with major burn. C1 esterase inhibitor activity after burn dropped acutely on days 1 and 2 but increased immediately until days 3 to 5, after which it continued to gradually increase to above the reference value. C1 esterase inhibitor activity on admission showed significant inverse correlation with the volume of infusion per body weight required in the first 24 hours after injury and %TBSA burned (r = -0.405, P = 0.01; r = -0.375, P = 0.02, respectively). C1 esterase inhibitor activity on admission was significantly lower in the nonsurvivors than in the survivors during the 28-day evaluation period (59% vs 90%, P = 0.01). These findings suggest that C1 esterase inhibitor may play a critical role in regulating vascular permeability in the acute phase following the burn injury.


Measurement of intraocular pressure over a gel lens.
Tonometric measurements of albino rabbits were determined with and without the use of a gel lens while the intraocular pressure (IOP) was manometrically controlled. The IOP was evaluated over a 50-mm Hg range of pressures. A high degree of correlation between measurements made with and without a gel lens was found. The results suggest that the technique may have clinical applications on patients for whom a corneal anesthesia is contraindicated or on whom repeated tonometry or tonography might cause corneal trauma.


The effect of preceding context on inhibition: an event-related fMRI study.
In this study we combined event-related fMRI with a parametric manipulation of the go nogo paradigm to examine the effect of preceding context on inhibitory processes. Nogo trials were preceded by either 1, 3, or 5 go trials and then compared to one another. Two distinct patterns of activation were associated with behavioral inhibition: First, the ventral prefrontal cortex, cingulate gyrus, and superior parietal regions showed a context effect with an increase in MR signal to nogo trials with increasing number of preceding go trials. Second, anterior regions in the supplementary and premotor cortex showed an increase in MR signal on the nogo condition after 5 preceding go trials, but not after only 1 or 3. A model using the BOLD response in our data was used to verify that the effect of context was not an artifact of the randomization scheme used in the design.


Venous shunting as a complication to penile revascularization--a case report.
As a serious complication to arterial penile revascularisation arterio-venous shunting was observed in a 60 years old male. The patient suffered bilateral obstruction of his pudendal arteries. Following revascularization using the left inferior epigastric artery he obtained good pulsation in the penis but no return of sexual function. Instead his general condition deteriorated. A follow-up angiogram revealed shunting of the contrast from the epigastric artery, via the penis, to the venous system. Venous ligation was carried out. The patient's general condition returned to normal status and he can now obtain rigid erections. Reconstructive arterial surgery for erectile dysfunction should never be carried out unless venous leak has been ruled out as a complicating factor.


Combustion Chemistry of Fuels: Quantitative Speciation Data Obtained from an Atmospheric High-temperature Flow Reactor with Coupled Molecular-beam Mass Spectrometer.
This manuscript describes a high-temperature flow reactor experiment coupled to the powerful molecular beam mass spectrometry (MBMS) technique. This flexible tool offers a detailed observation of chemical gas-phase kinetics in reacting flows under well-controlled conditions. The vast range of operating conditions available in a laminar flow reactor enables access to extraordinary combustion applications that are typically not achievable by flame experiments. These include rich conditions at high temperatures relevant for gasification processes, the peroxy chemistry governing the low temperature oxidation regime or investigations of complex technical fuels. The presented setup allows measurements of quantitative speciation data for reaction model validation of combustion, gasification and pyrolysis processes, while enabling a systematic general understanding of the reaction chemistry. Validation of kinetic reaction models is generally performed by investigating combustion processes of pure compounds. The flow reactor has been enhanced to be suitable for technical fuels (e.g. multi-component mixtures like Jet A-1) to allow for phenomenological analysis of occurring combustion intermediates like soot precursors or pollutants. The controlled and comparable boundary conditions provided by the experimental design allow for predictions of pollutant formation tendencies. Cold reactants are fed premixed into the reactor that are highly diluted (in around 99 vol% in Ar) in order to suppress self-sustaining combustion reactions. The laminar flowing reactant mixture passes through a known temperature field, while the gas composition is determined at the reactors exhaust as a function of the oven temperature. The flow reactor is operated at atmospheric pressures with temperatures up to 1,800 K. The measurements themselves are performed by decreasing the temperature monotonically at a rate of -200 K/h. With the sensitive MBMS technique, detailed speciation data is acquired and quantified for almost all chemical species in the reactive process, including radical species.


The (•)OH radical yield in the H2O2 + O3 (peroxone) reaction.
The peroxone process is one of the AOPs that lead to (•)OH. Hitherto, it has been generally assumed that the (•)OH yield is unity with respect to O3 consumption. Here, experimental data are presented that suggest that it must be near 0.5. The first evidence is derived from competition experiments. The consumption of 4-chlorobenzoic acid (4-CBA), 4-nitrobenzoic acid (4-NBA) and atrazine present in trace amounts (1 μM) has been followed as a function of the O3 concentration in a solution containing H2O2 (1 mM) and tertiary butanol (tBuOH, 0.5 mM) in excess over the trace compounds. With authentic (•)OH generated by γ-radiolysis such a competition can be adequately fitted by known (•)OH rate constants. Fitting the peroxone data, however, the consumption of the trace indicators can only be rationalized if the (•)OH yield is near 0.5 (4-CBA: 0.56, 4-NBA: 0.49, atrazine: 0.6). Additional information for an (•)OH yield much below unity has been obtained by a product analysis of the reactions of tBuOH with (•)OH and dimethyl sulfoxide with (•)OH. The mechanistic interpretation for the low (•)OH yield is as follows (Merényi et al. Environ. Sci. Technol. 2010, 44, 3505-3507). In the reaction of O3 with HO2(-) an adduct (HO5(-)) is formed that decomposes into O3(•-) and HO2(•) in competition with 2 O2 + OH(-). The latter process reduces the free-radical yield.


[Clinical usefulness of the (1-->3)-beta-D-glucan measurement kit using the improved alkaline pretreatment method--comparison with conventional method].
We had reported that the rate of non-specific reaction in measurement of (1-->3)-beta-D-glucan was decreased by improvement of the alkaline pretreatment reagent of Fungitec G-test MK (MK assay). To compare the clinical usefulness between conventional MK assay and new MK assay using improved alkaline pretreatment reagent, 121 plasma samples were tested. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) in conventional MK assay were 91.7%, 85.3%, 44.0% and 98.8%, respectively. Those in new MK assay were 75.0%, 91.6%, 52.9% and 96.7%, respectively. On the other hand, area under the curve (AUC) of receiver operating characteristic (ROC) analysis in conventional and new MK assay was 0.9175 and 0.9123 without a significant difference. It has been recognized that the sensitivity in conventional MK assay is higher than those in other beta-glucan assays. Then, the specificity of new MK assay was improved by using improved alkaline pretreatment reagent, without decreasing the sensitivity. Thus, the present findings indicate that the new MK assay is clinically quite useful.


Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics.
A shift has occurred in the diagnostic and therapeutic modalities considered for patients with primary immunodeficiency diseases (PIDs). Early diagnosis remains the mainstay in appropriate management and remarkably influences the prognosis. More specific diagnostic tests as well as therapeutic modalities have been introduced in the last few decades. Nonetheless, the importance of a thorough history taking and physical examination should not be neglected. Novel diagnostic modalities including genetic sequencing have led to the recognition of previously unknown defects underlying PIDs. In addition, newborn screening is being advocated as an imperative diagnostic test. In terms of treatment, hematopoietic stem cell transplantation is considered the optimal treatment modality for many cases and has dramatically improved the outcome. Gene transfer into hematopoietic stem cells prior to transplantation has improved the efficacy of hematopoietic stem cell transplantation. In this article, the latest advances made in terms of diagnosis and treatment of PIDs are reviewed.


Microalbuminuria associated with systolic blood pressure and arterial compliance in Chinese metabolic syndrome patients.
There is significant evidence showing that microalbuminuria and arterial compliance are sensitive markers for early cardiovascular diseases. However, whether microalbuminuria is associated with reduced arterial compliance in Chinese metabolic syndrome (MS) patients remains unknown. According to the definition of MS proposed by ATPIII in 2001, USA, subjects (n = 362) were divided into three groups according to the number of risk factors: group 1 (control), group 2 (medium, < 3 risk factors) and group 3 (MS, = 3 risk factors). Both large artery compliance (C1) and small artery compliance (C2) were measured with the CVProfilor DO-2020 Cardiovascular Profiling System, and microalbuminuria was evaluated with the ratio of albumin to urine creatinine. (1) As C1 and C2 levels elasticity decreased, albumin creatinine ratio (ACR) and the prevalence of microalbuminuria increased within those groups with MS risk factors. C1 and C2 were negatively correlated with the ranking of MS risk factors, ACR was positively correlated with the ranking of MS risk factors (all P < 0.05). (2) Subjects were also categorized into a microalbuminuria group and a normal group, C1 and C2 in the microalbuminuria group were lower than in the normal group. (3) Multivariate regression analysis showed that increased systolic blood pressure (SBP) and reduced arterial compliance were the main risk factors for microalbuminuria in the MS group. The risk of developing microalbuminuria was higher in the subjects with multiple metabolic abnormalities. Increased systolic blood pressure and reduced arterial compliance may be the main predictors for microalbuminuria in MS.


Two coagulase-variant forms of Staphylococcus aureus isolated from blood cultures.
Two coagulase-variant forms of Staphylococcus aureus were isolated from blood cultures of a patient with infective endocarditis. The coagulase-positive isolate was hemolytic, whereas the coagulase-negative isolate was nonhemolytic. All other properties examined were identical in both strains. Since coagulase-negative S. aureus strains have been isolated from clinical specimens, laboratories should consider using a combination of other biological properties along with coagulase production for the identification of S. aureus.


Observation of Charge Generation and Transfer during CVD Growth of Carbon Nanotubes.
Carbon nanotube (CNT) is believed to be the most promising material for next generation IC industries with the prerequisite of chirality specific growth. For various approaches to controlling the chiral indices of CNTs, the key is to deepen the understanding of the catalytic growth mechanism in chemical vapor deposition (CVD). Here we show our discovery that the as-grown CNTs are all negatively charged after Fe-catalyzed CVD process. The extra electrons come from the charge generation and transfer during the growth of CNTs, which indicates that an electrochemical process happens in the surface reaction step. We then designed an in situ measurement equipment, verifying that the CVD growth of CNTs can be regarded as a primary battery system. Furthermore, we found that the variation of the Fermi level in Fe catalysts have a significant impact on the chirality of CNTs when different external electric fields are applied. These findings not only provide a new perspective on the growth of CNTs but also open up new possibilities for controlling the growth of CNTs by electrochemical methods.


Noninvasive assessment of metabolic turnover during inflammation by in vivo deuterium magnetic resonance spectroscopy.
Inflammation and metabolism exhibit a complex interplay, where inflammation influences metabolic pathways, and in turn, metabolism shapes the quality of immune responses. Here, glucose turnover is of special interest, as proinflammatory immune cells mainly utilize glycolysis to meet their energy needs. Noninvasive approaches to monitor both processes would help elucidate this interwoven relationship to identify new therapeutic targets and diagnostic opportunities. For induction of defined inflammatory hotspots, LPS-doped Matrigel plugs were implanted into the neck of C57BL/6J mice. Subsequently, 1H/19F magnetic resonance imaging (MRI) was used to track the recruitment of 19F-loaded immune cells to the inflammatory focus and deuterium (2H) magnetic resonance spectroscopy (MRS) was used to monitor the metabolic fate of [6,6-2H2]glucose within the affected tissue. Histology and flow cytometry were used to validate the in vivo data. After plug implantation and intravenous administration of the 19F-containing contrast agent, 1H/19F MRI confirmed the infiltration of 19F-labeled immune cells into LPS-doped plugs while no 19F signal was observed in PBS-containing control plugs. Identification of the inflammatory focus was followed by i.p. bolus injection of deuterated glucose and continuous 2H MRS. Inflammation-induced alterations in metabolic fluxes could be tracked with an excellent temporal resolution of 2 min up to approximately 60 min after injection and demonstrated a more anaerobic glucose utilization in the initial phase of immune cell recruitment. 1H/2H/19F MRI/MRS was successfully employed for noninvasive monitoring of metabolic alterations in an inflammatory environment, paving the way for simultaneous in vivo registration of immunometabolic data in basic research and patients.


Spectrum of microbial flora in diabetic foot ulcers.
A prospective study was carried out on patients with diabetic foot lesions to determine their clinical characteristics, the spectrum of aerobic microbial flora and to assess their comparative in vitro susceptibility to the commonly used antibiotics. A total of 157 organisms (143 bacteria and 14 fungi) were isolated and an average of 1.52 isolates per case was reported. Polymicrobial infection was found in 35% of the patients. In this study, Pseudomonas aeruginosa among the gram-negative (22%) and Staphylococcus aureus among the gram-positive (19%) were the predominantly isolated organisms, while Candida was the most predominantly isolated fungus. Antimicrobial sensitivity pattern of the isolates is discussed in detail. There was a linear increase in the prevalence of organisms with increase in Wagner's grade. Neuropathy (76%) and peripheral vascular disease (57.28%) was a common feature among the patients. Poor glycemic control was found in 67% of the patients. Awareness about lower limb complications of diabetes was very low (23%) among the patients.


The Effect of Preoperative Rehabilitation Training on the Early Recovery of Joint Function after Artificial Total Knee Arthroplasty and Its Effect Evaluation.
To study the effect of preoperative rehabilitation training on the rehabilitation of patients after total knee arthroplasty. A total of 120 patients diagnosed with knee osteoarthritis and undergoing total knee arthroplasty were selected and divided into experimental group and control group according to a random number table, with 60 cases in each group. The control group only carried out routine clinical nursing before the operation, and the experimental group used the formulated preoperative rehabilitation training method based on the control group for training. By comparing the visual analogue score (VAS), keen society score (KSS), postoperative time to get out of bed for the first time, patient satisfaction, and other related indicators between the two groups of patients, the recovery of keen joint function of patients after surgery was evaluated. The visual analogue scale (VAS) of the experimental group was significantly lower than that of the experimental group at three days after operation. The keen society score (KSS) of the experimental group was significantly better than that of the control group at three days after surgery and one month after surgery. The time to get out of bed for the first time after operation in the experimental group (44.93 ± 13.63) was significantly less than that in the control group (78.33 ± 13.52). The patient satisfaction of the experimental group was significantly higher than that of the control group (88.30 ± 3.61). The above statistical results were all p < 0.05 of the two groups, and the differences were statistically significant. Preoperative rehabilitation training can significantly reduce the pain of patients after knee replacement, improve the functional state of knee joints, shorten the time to get out of bed for the first time after surgery, and win the best recovery opportunity, which can better improve patient satisfaction in hospitalization and improve medical care services level.


Does receiving a cash grant improve individual earnings in a war-torn country? Evidence from a randomized experiment in Afghanistan.
In this paper, the effect of receiving a non-trivial cash grant and mentorship for business practice on individual earnings in Afghanistan was assessed. This randomized control trial(RCT) included 2177 individuals (n=2177), with the age range of 18-35 years. The amount of cash grant was approximately equal to the gross domestic product (GDP) per capita in the country (500 USD). By a process of lottery, eligible applicants were equally divided into the group that received the grant (treatment group) and the group that did not (control group). The regression estimation was conducted for the analysis. The percentage of increased annual income to the size of this cash grant almost two years after this study was approximately 173 % and 69 % for males and females, respectively. This result was much higher than the estimated percentage reported in previous literature assessing the effect of microfinance loans and cash grants in other countries. The treatment group had a 7 percentage point higher probability of having an officially registered business than the control group. The treatment group also increased labor supply and employed additional workers, compared to the control group. The male treatment group bought more capital equipment (e.g., trike and commercial carts) than the male control group, while the female treatment group bought more domestic animals. A non-trivial cash grant has a strong positive effect on the earnings of the recipient of the cash grant in Afghanistan. If the state of increased income continues for the next few years, the sum of increased income will be more than the sum of the administration cost, the interest cost and the amount of cash grant given. It implies that the project passes the standard criteria to determine the appropriateness of government program. Additionally, we did not find any economically and statistically significant positive effect of mentorship on income.


[Endocrine, paracrine and electrophysiologic regulation of human labor].
The problem of labor and delivery, either at term or occurring prematurely, are among the greatest problems facing physicians nowadays. The understanding of the process of preparation and initiation of active labor is of utmost importance. Currently, the clinical methods to assess the changes of the uterus and cervix are still subjective, inaccurate and crude. Fortunately, a noninvasive method of transabdominal uterine muscle electrical activity analysis (electromiography, EMG) is digitalized and standardized in recognizing uterine contractility, and biochemical changes, as well as ultrasound and fluorescent methods, are emerging to estimate cervical preparation prior to active labor. Studies in humans indicate that uterine and cervical function an be accurately monitored during pregnancy and during the preparation for labor. In the review article all aspects of uterine muscle and uterine cervix architecture, preparation for labor and control of these processes are presented. The development of new methods of diagnosis for the patient in labor will improve our ability to diagnose preterm labor early enough to undertake all kinds of scientifically based methods and strategies specifically for the management of this condition.


Biliary Complications After Liver Transplantation in the United States: Changing Trends and Economic Implications.
Biliary complications (BCs) continue to impact patient and graft survival after liver transplant (LT), despite improvements in organ preservation, surgical technique, and posttransplant care. Real-world evidence provides a national estimate of the incidence of BC after LT, implications for patient and graft outcomes, and attributable cost not available in transplant registry data. An administrative health claims-based BC identification algorithm was validated using electronic health records (N = 128) and then applied to nationally linked Medicare and transplant registry claims. The real-world evidence algorithm identified 97% of BCs in the electronic health record review. Nationally, the incidence of BCs within 1 y of LT appears to have improved from 22.2% in 2002 to 20.8% in 2018. Factors associated with BCs include donor type (living versus deceased), recipient age, diagnosis, prior transplant, donor age, and donor cause of death. BCs increased the risk-adjusted hazard ratio (aHR) for posttransplant death (aHR, 1.43; P < 0.0001) and graft loss (aHR, 1.48; P < 0.0001). Nationally, BCs requiring intervention increased risk-adjusted first-year Medicare spending by $39 710 ( P < 0.0001). BCs remain an important cause of morbidity and expense after LT and would benefit from a systematic quality-improvement program.


RORgammat recruits steroid receptor coactivators to ensure thymocyte survival.
Thymocytes undergo apoptosis unless a functional TCR is assembled. Steroid receptor coactivators (SRCs) regulate nuclear receptor-mediated transcription by associated histone acetyltransferase activity. However, it has been a challenge to demonstrate the in vivo function of SRCs due to the overlapping functions among different members of SRCs. In this study, we show that recruitment of SRCs is required for thymic-specific retinoic acid-related orphan receptor gamma (RORgamma)t-regulated thymocyte survival in vivo. An activation function 2 domain, identified at the carboxyl terminus of RORgammat, is responsible for recruiting SRCs. A mutation in the activation function domain (Y479F) of RORgammat disrupted the interaction with SRCs and abolished RORgammat-mediated trans-activation but not its ability to inhibit transcription. Transgenes encoding the wild-type RORgammat, but not the mutant, restored thymocyte survival in RORgamma null mice. Our results thus clearly demonstrate that RORgammat recruits SRCs to impose a gene expression pattern required to expand the life span of thymocytes in vivo, which increases the opportunities for assembling a functional TCR.


[Predictive markers of immunotherapy of cancer, practical issues of PD-L1 testing].
Pathologists have detected signs of antitumor immune reactions for a long time but only in case of a few cancer types became this part of the report. The advent of immunotherapy of cancers, however, radically alters this routine and promotes the development of clinically valid prognostic and predictive immunological makers. The most advanced immunological markers are the Immunoscore (density of T-cell subpopulations), and PD-L1 protein expression on tumor or immune cells. PD-L1 testing of cancers raises new issues since almost all novel therapies developed its own in vitro diagnostics. Due to the incompatibility of these assays it is suggested to use the companion diagnostic of the given immunotherapeutic drug defined in its label.


Reduced-dose prasugrel monotherapy without aspirin after PCI with the SYNERGY stent in East Asian patients presenting with chronic coronary syndromes or non-ST-elevation acute coronary syndromes: rationale and design of the ASET Japan pilot study.
The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.


Contribution of transmembrane regions to ATP-gated P2X2 channel permeability dynamics.
ATP-gated P2X(2) channels undergo activation-dependent permeability increases as they proceed from the selective I(1) state to the I(2) state that is readily permeable to organic cations. There are two main models about how permeability changes may occur. The first proposes that permeability change-competent P2X channels are clustered or redistribute to form such regions in response to ATP. The second proposes that permeability changes occur because of an intrinsic conformational change in P2X channels. In the present study we experimentally tested these views with total internal reflection fluorescence microscopy, electrophysiology, and mutational perturbation analysis. We found no evidence for clusters of P2X(2) channels within the plasma membrane or for cluster formation in response to ATP, suggesting that channel clustering is not an obligatory requirement for permeability changes. We next sought to identify determinants of putative intrinsic conformational changes in P2X(2) channels by mapping the transmembrane domain regions involved in the transition from the relatively selective I(1) state to the dilated I(2) state. Initial channel opening to the I(1) state was only weakly affected by Ala substitutions, whereas dramatic effects were observed for the higher permeability I(2) state. Ten residues appeared to perturb only the I(1)-I(2) transition (Phe(31), Arg(34), Gln(37), Lys(53), Ile(328), Ile(332), Ser(340), Gly(342), Trp(350), Leu(352)). The data favor the hypothesis that permeability changes occur because of permissive motions at the interface between first and second transmembrane domains of neighboring subunits in pre-existing P2X(2) channels.


Laparoscopic one port appendectomy: Evaluation in pediatric surgery.
Appendectomy is a well-established surgical procedure in pediatric surgery used in the management of acute appendicitis. With the continuous advancement in the field of minimal invasive surgery, the recent focus is on single incision laparoscopic (SIL) surgery. SILA also goes further in order to decrease pain, improve recovery and enhance patient satisfaction. However, this approach is still not a well-established technique and not widely practiced, especially in pediatric surgery. We prospectively recorded the data in our pediatric universitary hospital center since January, 01 2017 to July, 01 2017. Patients included in this study were randomized in two groups: SILA group (managed by one-port laparoscopy, n=40) and LA group (conventional laparoscopy using three trocars, n=40). The mean operative time for SILA was significantly lower. There were no postoperative complications in SILA group. If peritonitis was associated with appendicitis, the operative duration was not significantly different between each group. The duration in recovery room after surgery was significantly lower in SILA group. The morphine consumption was significantly lower for SILA group according to patient weight. SILA is less painful significantly than CLA for the first postoperative 6 h. After, even if SILA appears less painful, difference is not significant. The hospital length of stay was significantly higher in LA than SILA group CONCLUSIONS: SILA procedure for appendectomy appears to be safe and efficient for appendicitis management in children. This technique could be applied in routine as in emergency tome. Prospective comparative study LEVEL OF EVIDENCE: II.


Influence of nicotinic receptor modulators on CB2 cannabinoid receptor agonist (JWH133)-induced antinociception in mice.
Delta9-tetrahydrocannabinol is the active component in cannabis and has long been associated with pain relief. This effect is believed to be mediated through central and peripheral CB1 and peripheral CB2 receptors. We have explored the possible antinociceptive effect of a CB2 receptor agonist, JWH133, using the formalin test in mice. The drug was administered by the intracerebroventricular and intraperitoneal routes. Although no antinociceptive effect was observed after intracerebroventricular administration of JWH133, when the drug was administered by the intraperitoneal route, it produced an analgesic effect. The influence of nicotinic cholinergic receptor modulators, nicotine and mecamylamine, on antinociceptive effect of JWH133 was also studied. Nicotine increased and mecamylamine decreased the antinociceptive effect of JWH133. It is concluded that JWH133-induced analgesia is influenced by nicotinic cholinergic receptor activity.


Is p16(INK4a) protein expression in oral ST lesions a reliable precancerous marker?
This study correlates the expression of p16(INK4a) and p53 with the detection of high risk human papillomavirus (HPV) in three clinical grades of smokeless tobacco keratosis (STK) as compared with patients without a history of smokeless tobacco use. Tissue samples, including squamous cell carcinoma (SCC) were evaluated for the expression of p16(INK4a) and p53 by indirect immunohistochemical methods using commercially obtained antibodies. HPV DNA analysis was performed using consensus sequence polymerase chain reaction (PCR). At least focal p16(INK4a) expression was detected in Grade I, II and III STK, SCC and control samples of alveolar ridge keratoses (ARK). p16(INK4a) expression in STK and in ARK was typically weak but was relatively strong in all SCC. Strong p53 nuclear staining was detected in STK, SCC and ARK. HPV DNA was detected in Grade I, II and III STK, SCC and ARK, but did not correlate with p16(INK4a) expression. p16(INK4a) distribution did not correlate with STK grade and does not appear to be related to the detection of HPV DNA by PCR in either STK or in SCC. There is an apparent relationship between the grade of STK and the presence of HPV. HPV was rarely detected in high-grade lesions.


What the patient should order.
Open global standards, workflow integration profiles, and related processes have been developed through consensus-based procedures. Although these standards and profiles should be augmented with additional therapeutic area-based content standards, they are available now to enable the use of electronic health records to directly support clinical research concurrent with patient care. Improving the exchange of information and integrating workflow between research and health care are inherently necessary to accelerate the pace of informing clinical decisions based on current research findings and for an efficient, cost-effective health care system to improve the quality of patient care.


Accuracy of inertial motion sensors in static, quasistatic, and complex dynamic motion.
Inertial motion sensors (IMSs) combine three sensors to produce a reportedly stable and accurate orientation estimate in three dimensions. Although accuracy has been reported within the range of 2 deg of error by manufacturers, the sensors are rarely tested in the challenging motion present in human motion. Their accuracy was tested in static, quasistatic, and dynamic situations against gold-standard Vicon camera data. It was found that static and quasistatic rms error was even less than manufacturers' technical specifications. Quasistatic rms error was minimal at 0.3 deg (+/-0.15 deg SD) on the roll axis, 0.29 deg (+/-0.20 deg SD) on the pitch axis, and 0.73 deg (+/-0.81 deg SD) on the yaw axis. The dynamic rms error was between 1.9 deg and 3.5 deg on the main axes of motion but it increased considerably on off-axis during planar pendulum motion. Complex arm motion in the forward reaching plane proved to be a greater challenge for the sensors to track but results are arguably better than previously reported studies considering the large range of motion used.


Receptor tyrosine kinase profiles and human papillomavirus status in oropharyngeal squamous cell carcinoma.
Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OSCCs) are two distinct entities. We defined the molecular profiles of druggable receptor tyrosine kinases (RTKs) in both groups. E5 expression and RTK alterations were studied in 17 HPV-positive and 59 HPV-negative formalin-fixed OSCCs. RTK activation was explored in further 12 frozen OSCCs. The HPV-positive OSCCs showed E5 expression and 33.3% expressed low level of HER2. The HPV-negative OSCCs showed HER2 expression (31.2%), increased HER2 gene copy number (46.51%, P = 0.045) and HER2 activation through HER2/EGFR heterodimerisation; HER3 (51.06%, P = 0.008) and neuregulin (65.63%; P = 0.03) expression, HER3 activation and HER3/EGFR heterodimerisation; and increased IGF-1R copy number (40.50%, P = 0.021), high IGF-1R cDNA values (P = 0.002), IGF-1R activation and expression of IGF1/2 and amphiregulin. PI3KCA mutations/expression/increased gene copy number and PTEN mutations were found in both groups, whereas PTEN gene loss was only observed in the HPV-positive cases. Human papillomavirus-positive and HPV-negative OSCC showed different RTK profiles. In HPV-positive cases, it would be interesting to study the expression of E5, which may modulate EGFR turnover and activate VEGF and PDGFRβ. In HPV-negative cases, HER3 may be a promising druggable biomarker that deserves further investigation. PI3KCA and PTEN alterations encourage the promising clinical evaluation of PI3K/mTOR inhibitor activity in OSCC, particularly in HPV-positive/PI3KCA-mutated OSCCs because they may be driven by PI3KCA mutation alone.


First-principles electronic structure study of the monoclinic crystal bismuth triborate BiB3O6.
Monoclinic BiB(3)O(6) is an excellent nonlinear optical material with many advantages compared to other borate crystals. The origins of the optical effects and the chemical stability of BiB(3)O(6) are studied with gradient-corrected hybrid B3PW density functional theory within the Gaussian-orbital-based CO-LCAO scheme. Including spin-orbit coupling, the B3PW hybrid functional provides an estimate of the indirect band gap of 4.29-4.99 eV closer to the experimental value of 4.3 eV than HF, LDA, or GGA. The crystal orbital overlap population to give a detailed first-principles analysis of chemical bonding and the density of optical absorptions by convoluting the occupied density of states and the virtual density of states have been calculated. Obvious Bi-O covalent bonds have been found with different energy ranges for 6s-2p and 6p-2p interactions. The reason that [BiO(4)](5-) units are mainly responsible for the optics of BiB(3)O(6) in the long-wavelength region is due to the electronic transfer from occupied O 2p to empty Bi 6p orbitals favored by the Bi-O covalent bonds. The relativistic and correlation effects lead to fundamental differences of the band structure, chemical bonds, and optical effects for BiB(3)O(6) compared with nonrelativistic and uncorrelated calculations.


The automatic recognition and counting of cough.
Cough recordings have been undertaken for many years but the analysis of cough frequency and the temporal relation to trigger factors have proven problematic. Because cough is episodic, data collection over many hours is required, along with real-time aural analysis which is equally time-consuming. A method has been developed for the automatic recognition and counting of coughs in sound recordings. The Hull Automatic Cough Counter (HACC) is a program developed for the analysis of digital audio recordings. HACC uses digital signal processing (DSP) to calculate characteristic spectral coefficients of sound events, which are then classified into cough and non-cough events by the use of a probabilistic neural network (PNN). Parameters such as the total number of coughs and cough frequency as a function of time can be calculated from the results of the audio processing. Thirty three smoking subjects, 20 male and 13 female aged between 20 and 54 with a chronic troublesome cough were studied in the hour after rising using audio recordings. Using the graphical user interface (GUI), counting the number of coughs identified by HACC in an hour long recording, took an average of 1 minute 35 seconds, a 97.5% reduction in counting time. HACC achieved a sensitivity of 80% and a specificity of 96%. Reproducibility of repeated HACC analysis is 100%. An automated system for the analysis of sound files containing coughs and other non-cough events has been developed, with a high robustness and good degree of accuracy towards the number of actual coughs in the audio recording.


Preexisting Bipolar Disorder Influences the Subsequent Phenotype of Parkinson's Disease.
Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


In vitro alkylating of alpha, beta-unsaturated amidoesters, diethyl pyridylmethylphosphonates and their cis-Pt(II)complexes.
The alkylating ability of alpha,beta-unsaturated amidoesters 1a-8d, diethyl pyridylmethylphosphonate esters and their cis-platinum(II) complexes has been investigated based on the test with 4-(4'-nitrobenzyl)pyridine (NBP) (Preussmann Test). Of the compounds tested for alkylating activity, only cis-platinum(II) phosphonate complexes were found to possess activity. The highest activity was found for CiS-[PtCl2(4-pmpe)2] where 4-pmpe is diethyl 4-pyridylmethylphosphonate. The results show a correlation between alkylating activity in vitro and cytotoxic activity in vivo for platinum(II) complexes.


Optimization of microflow LC-MS/MS and its utility in quantitative discovery bioanalysis.
Aim: The sensitivity advantage of microflow LC (μFLC)-MS/MS is potentially impactful for challenging compounds not detectable by conventional flow LC-MS/MS in drug discovery bioanalysis. Relatively new to μFLC technology, discovery bioanalytical scientists would benefit from an effective strategy for method development and optimization. Results: A systematic μFLC-MS/MS method optimization approach was developed in this study. With optimized conditions, μFLC-MS/MS demonstrated an improved sensitivity compared with conventional LC-MS/MS analysis, ranging from 6× to 49× (by peak area) depending on the compounds, with acceptable analytical performance and robustness. The optimized conditions demonstrated universal applicability to various compounds of diverse properties. Conclusion: The systematic method optimization strategy, and the general applicability of the optimized conditions could facilitate the routine utilization of μFLC in quantitative discovery bioanalysis.


Analysis of Different Positions of Fiber-Reinforced Composite Retainers versus Multistrand Wire Retainers Using the Finite Element Method.
Background. The aim of this study was to evaluate root displacement of the lower incisors fixed with FRC in different positions versus FSW retainers using the finite element method. Materials and Methods. 3D finite element models were designed for a mandibular anterior segment: Model 1: flexible spiral wire bonded to the lingual teeth surfaces, Model 2: FRC bonded to the upper third of lingual teeth surfaces, and Model 3: FRC bonded to the middle third. FE analysis was performed for three models and then tooth displacements were evaluated. Results. In contrast to lateral incisors and canines, the FSW retainer caused the central teeth to move more than the teeth bonded with FRC in both loadings. Comparison between Models 2 and 3 (in vertical loading) showed that FRC retainers that bonded at the upper third of lingual teeth surfaces made central and canine teeth move less than FRC retainers bonded at the middle third; however, for lateral teeth it was the opposite. Conclusion. FRC retainers bonded at the upper third of lingual teeth surfaces make central and canine teeth move less than FRC retainers bonded at the middle third in vertical loading; however, for lateral teeth it was the opposite.


Significance of blood-tinged post-nasal drip in paranasal sinus disease.
Blood-tinged post-nasal drip is a rare manifestation of paranasal sinus disease. Although the presence of such a symptom would intuitively prompt suspicion of malignancy, no previously published study has addressed this issue. One hundred and ninety-three patients with paranasal sinus lesions, who had undergone endoscopic sinus surgery for treatment or biopsy, were prospectively recruited. Their clinical information was collected and analysed. In patients without blood-tinged post-nasal drip, 177/181 (97.8 per cent) had chronic paranasal sinusitis and fungal sinusitis. However, in patients who presented with this symptom, six of 12 (50 per cent) were diagnosed with other conditions. The difference was statistically significant (Fisher's exact test, two tails, p < 0.001). In patients with blood-tinged post-nasal drip, diagnoses other than chronic paranasal sinusitis and fungal sinusitis were found more frequently in older males. The chance of diagnoses other than the usual sinusitis increased significantly in patients with paranasal sinus diseases who presented with blood-tinged post-nasal drip, especially in older males.


Educating patients with diabetes about cardiovascular disease risk.
In persons with diabetes mellitus, atherosclerosis is increased, develops prematurely, and is associated with an accelerated progression of atherosclerotic changes. More than 55% of deaths from diabetes are from cardiovascular disease. Central to the optimal management of diabetes and the prevention of chronic complications is effective patient education. The necessity of optimal glycemic control in the prevention of long-term diabetes-related complications, particularly microvascular disease, has been a primary focus of diabetes education during the past decade. It has become clear that to prevent cardiovascular disease in persons with diabetes, an increased emphasis on patient education aimed at reducing cardiovascular disease risk factors is essential. This review explores the scope, impact, and prevention of diabetes-related cardiovascular disease, focusing on integration of cardiovascular disease risk reduction during patient teaching and education programs.


Puberty blockade: Clinical guideline for the diagnosis and treatment of precocious puberty.
The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the interventions for the inhibition of central precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be consulted in this same supplement.


[Neurological complications of anticancer treatments].
After bone marrow toxicity, neurological toxicities are the second most common complications of cancer. They can be observed throughout the course of the disease or even after the end of treatment. Establishing the correct diagnosis may be a challenge but is of outmost importance to minimize the risk of long-term neurological deficits and to improve the quality of life of the patients. This review will focus on neurological complications induced by chemotherapeutic agents. As the life expectancy and number of treatment lines used in cancer patients increases, these complications are bound to become more frequent and should be aware to neurologists.


User evaluation: PA catheter waveforms troubleshooting system.
This paper reports on a user satisfaction survey of a system for consultation and education in troubleshooting pulmonary artery catheter waveforms. The twelve-item End-User Computing Satisfaction Questionnaire was used to assess users' ratings in four areas. On a scale of 1-5 (with 1 the lowest), the ratings were: Content, 3.5; Accuracy, 4.5; Format, 4.2; Ease of Use, 4.4, and Timeliness, 4.1. Comparison with ratings in a survey that included a variety of applications and settings is provided.


Relationship of lactose intolerance to milk intolerance in young children.
The prevalence of lactose intolerance as revealed by the standard lactose tolerance test was compared with the occurrence of intolerance to graded amounts of milk in 69 black and 30 white children. Of the black children studied, 11% of those 4 to 5 years old, 50% of those 6 to 7 years old, and 72% of those 8 to 9 years old were found to be lactose-intolerant, yet no child was intolerant to 240 ml of milk. Symptom responses to greater amounts of milk did not suggest that the frequency of primary lactose intolerance might be a reason for limiting existing milk programs for young children. No significant differences were found between the milk intakes of black lactose-tolerant and black lactose-intolerant children, nor between milk intakes of 6- and 7-year-old black and white children in Boston. However, 8- to 9-year-old black children drank significantly less milk than 8- to 9-year-old white children did. The blood glucose response at 0, 20, and 45 min after the ingestion of 2 g lactose/kg (maximum 50 g) was unreliable as an indicator of an individual's symptomatic response to lactose.


Site-directed glycosylation tagging of functional Kir2.1 reveals that the putative pore-forming segment is extracellular.
Inwardly rectifying K+ channels or Kirs are a large gene family and have been predicted to have two transmembrane segments, M1 and M2, intracellular N and C termini, and two extracellular loops, E1 and E2, separated by an intramembranous pore-forming segment, H5. H5 contains a stretch of eight residues that are similar in voltage-dependent K+ channels, Kvs, and this stretch is called the signature sequence of K+ channels. Because mutations in this sequence altered selectivity in Kvs, it has been designated as the selectivity filter. Previously, we used N-glycosylation substitution mutants to map the extracellular topology of a weak inwardly rectifying K+ channel, Kir1.1 or ROMK1, and found that the entire H5 segment was extracellular. We now report utilization of introduced N-glycosylation sites, NX(S/T), at positions Ser(128) in E1, and Gln(140), Ileu(143), and Phe(147) in the H5 sequence of a strong inwardly rectifying K+ channel, Kir2.1. Furthermore, we show that biotinylated channel proteins with N-linked oligosaccharides attached at positions 140 and 143 in the signature sequence are located at the cell surface. Mutant channels were functional as detected by whole-cell and single-channel recordings. Unlike Kir1.1, position Lys(117) was not occupied. We conclude that, for yet another K+ channel, the invariant G(Y/F)G sequence is extracellular rather than intramembranous.


PLCγ1-PKCε-IP3R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells.
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in pulmonary arteries, but not in mesenteric arteries. Hypoxia caused a large increase in [Ca2+]i in PASMCs, which is diminished by the PLC inhibitor U73122 and not by its inactive analog U73433 . Hypoxia augments PLCγ1-dependent inositol 1,4,5-trisphosphate (IP3) generation. Exogenous ROS, hydrogen peroxide (H2O2), increases PLCγ1 phosphorylation at tyrosine-783 and IP3 production. IP3 receptor-1 (IP3R1) knock-down remarkably diminishes hypoxia- or H2O2-induced increase in [Ca2+]i. Hypoxia or H2O2 increases the activity of IP3Rs, which is significantly reduced in protein kinase C-ε (PKCε) knockout PASMCs. A higher PLCγ1 expression, activity, and basal [Ca2+]i are found in PASMCs, but not in mesenteric artery smooth muscle cells from mice exposed to chronic hypoxia (CH) for 21 days. CH enhances H2O2- and ATP-induced increase in [Ca2+]i in PASMCs and PLC-dependent, norepinephrine-evoked pulmonary vasoconstriction. In conclusion, acute hypoxia uniquely causes ROS-dependent PLCγ1 activation, IP3 production, PKCε activation, IP3R1 opening, Ca2+ release, and contraction in mouse PASMCs; CH enhances PASM PLCγ1 expression, activity, and function, playing an essential role in pulmonary hypertension in mice.


Ideonella alba sp. nov. and Ideonella aquatica sp. nov. isolated from an aquaculture farm.
The three novel bacterial strains designated as 3Y2T, 4Y16 and 4Y11T were isolated from an aquaculture farm and characterized using a polyphasic taxonomic approach. These strains were determined to be catalase- and oxidase-positive and to hydrolyze gelatin and aesculin. The results of 16S rRNA gene-based phylogenetic analysis indicated that the three strains were related to members of the genus Ideonella. The phylogenomic results further indicated that the three strains formed two independent branches distinct from reference type strains within this genus. The digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and average amino acid identity (AAI) values between the three strains and their relatives were far below the thresholds of 70 % dDDH, 95-96 % ANI and 95 % AAI for species definition, respectively, indicating that the three strains represent two novel genospecies. The results of chemotaxonomic characterization indicated that the major cellular fatty acids of the three strains were summed feature 3 (C16 : 1ω6c and/or C16 : 1 ω7c) and C16 : 0; the common main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol; the respiratory quinone was ubiquinone-8. The genomic DNA G+C contents of the three strains were 70.2, 70.1 and 69.7%, respectively. On the basis of the different genotypes and distinctive phenotypes such as the phosphatidylcholine and glycolipid only in 3Y2T and the utilization of malic acid and trisodium citrate only in 4Y11T, strains 3Y2T and 4Y11T are concluded to represent two novel species of the genus Ideonella, for which the names Ideonella alba sp. nov. (type strain 3Y2T = GDMCC 1.2584T = KCTC 82813T) and Ideonella aquatica sp. nov. (type strain 4Y11T = GDMCC 1.1935T = JCM 34285T) are proposed.


[Chemotherapeutic studies on litomosoides carinii infection of mastomys natalensis. 5. Alterations of haematological parameters after the administration of filaricidal compounds (author's transl)].
The peripheral blood picture of multimammate rats (Mastomys natalensis) infected with Litomosoides carinii was studied. Changes were followed in patent infections from 64 to 176 days after infection in animals treated with diethylcarbamazine (5 x 100 mg/kg per os), HOE 258 V (5 X 10 mg/kg subcutaneously), suramin (5 x 40 mg/kg subcutaneously) and with a combined treatment of diethylcarbamazine and suramin. In addition, haematological changes were followed in non-infected animals treated with suramin alone as well as in non-infected and infected animals receiving no treatment. During the course of non-treated L. carinii infection in Mastomys natalensis, animals developed anaemia, an increased sedimentation rate and a leucopenia. In addition there was a relative increase in circulating eosinophils, in large lymphocytes and monocytes and a relative decrease in small lymphocytes. After treatment with the microfilaricidal drugs diethylcarbamazine and HOE 258 V blood changes followed those of infection controls but there was a transient change towards normal in peripheral blood values when the microfilariaemia was reduced by the drugs. After treatment with the macrofilaricide suramin, nearly normal values were reached at the end of the experiment for the red blood cell and leucocytes levels. Combined treatment with suramin and diethylcarbamazine resulted in relatively normal levels for some parameters. Suramin was shown to cause haematological changes in normal animals which became evident several days before use of the drug. Such changes added to the pathological alterations caused by the filarial infection. In both infected and non-infected animals suramin treatment resulted in oedema around the nose and on the front feet approximately three weeks afterwards.


Two large-scale forest scenario modelling approaches for reporting CO2 removal: a comparison for the Romanian forests.
Forest carbon models are recognized as suitable tools for the reporting and verification of forest carbon stock and stock change, as well as for evaluating the forest management options to enhance the carbon sink provided by sustainable forestry. However, given their increased complexity and data availability, different models may simulate different estimates. Here, we compare carbon estimates for Romanian forests as simulated by two models (CBM and EFISCEN) that are often used for evaluating the mitigation options given the forest-management choices. The models, calibrated and parameterized with identical or harmonized data, derived from two successive national forest inventories, produced similar estimates of carbon accumulation in tree biomass. According to CBM simulations of carbon stocks in Romanian forests, by 2060, the merchantable standing stock volume will reach an average of 377 m3 ha-1, while the carbon stock in tree biomass will reach 76.5 tC ha-1. The EFISCEN simulations produced estimates that are about 5% and 10%, respectively, lower. In addition, 10% stronger biomass sink was simulated by CBM, whereby the difference reduced over time, amounting to only 3% toward 2060. This model comparison provided valuable insights on both the conceptual and modelling algorithms, as well as how the quality of the input data may affect calibration and projections of the stock and stock change in the living biomass pool. In our judgement, both models performed well, providing internally consistent results. Therefore, we underline the importance of the input data quality and the need for further data sampling and model improvements, while the preference for one model or the other should be based on the availability and suitability of the required data, on preferred output variables and ease of use.


Phenotypic and genotypic analysis of bio-serotypes of Yersinia enterocolitica from various sources in Brazil.
Yersinia enterocolitica is a well-known foodborne pathogen widely distributed in nature with high public health relevance, especially in Europe. This study aimed to analyze the pathogenic potential of Y. enterocolitica isolated strains from human, animal, food, and environmental sources and from different regions of Brazil by detecting virulence genes inv, ail, ystA, and virF through polymerase chain reaction (PCR), phenotypic tests, and antimicrobial susceptibility analysis. Pulsed-field gel electrophoresis (PFGE) was used for the assessment of phylogenetic diversity. All virulence genes were detected in 11/60 (18%) strains of serotype O:3, biotype 4 isolated from human and animal sources. Ten human strains (4/O:3) presented three chromosomal virulence genes, and nine strains of biotype 1A presented the inv gene. Six (10%) strains were resistant to sulfamethoxazole-trimethoprim, seven (12%) to tetracycline, and one (2%) to amikacin, all of which are used to treat yersiniosis. AMP-CEF-SXT was the predominant resistance profile. PFGE analysis revealed 36 unique pulsotypes, grouped into nine clusters (A to I) with similarity ≥ 85%, generating a diversity discriminatory index of 0.957. Cluster A comprised all bio-serotype 4/O:3 strains isolated from animal and humans sources. This study shows the existence of strains with the same genotypic profiles, bearing all virulence genes, from human and animal sources, circulating among several Brazilian states. This supports the hypothesis that swine is likely to serve as a main element in Y. enterocolitica transmission to humans in Brazil, and it could become a potential threat to public health as in Europe.


Structural and membrane binding properties of the prickle PET domain.
The planar cell polarity (PCP) pathway is required for fetal tissue morphogenesis as well as for maintenance of adult tissues in animals as diverse as fruit flies and mice. One of the key members of this pathway is Prickle (Pk), a protein that regulates cell movement through its association with the Dishevelled (Dsh) protein. Pk presents three LIM domains and a PET domain of unknown structure and function. Both the PET and LIM domains control membrane targeting of Dsh, which is necessary for Dsh function in the PCP pathway. Here, we show that the PET domain is monomeric and presents a nonglobular conformation with some properties of intrinsically disordered proteins. The PET domain adopts a helical conformation in the presence of 2,2,2-trifluoroethanol (TFE), a solvent known to stabilize hydrogen bonds within the polypeptide backbone, as analyzed by circular dichroism (CD) and NMR spectroscopy. Furthermore, we found that the conserved and single tryptophan residue in PET, Trp 536, moves to a more hydrophobic environment when accompanied with membrane penetration and that the protein becomes more helical in the presence of lipid micelles. The presence of LIM domains, downstream of PET, increases protein folding, thermostability, and tolerance to limited proteolysis. In addition, pull-down and tryptophan fluorescence analyses suggest that the LIM domains physically interact to regulate membrane penetration of the PET domain. The findings reported here favor a model where the PET domain is engaged in Pk membrane insertion, whereas the LIM domains modulate this function.


Fetal immune response to chorioamnionitis.
Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, gastrointestinal tract, brain, and other fetal organs. Chorioamnionitis is a polymicrobial nontraditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection-related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis-induced injury in different fetal compartments. As chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses.


Single-mode 212 W tapered fiber laser pumped by a low-brightness source.
With a tapered double-clad all-glass ytterbium fiber as a gain medium, a maximum output power of over 200 W at 1079 nm and a slope efficiency of over 70% were demonstrated. The tapered double-clad fiber concept allows for using low-brightness diode bars and results in cost-effective and efficient high-power fiber lasers. The adiabatic conical fiber gain waveguide combines improved pump absorption owing to enhanced mode mixing in the pump cladding, low-noise single fundamental mode operation with M(2)< or =1.02, and strong potential for significant power scaling.


Focal Adhesion Kinase as a Potential Target in AML and MDS.
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 × 10-4) and relapse (P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3-ITD (P = 0.0024) or RAS (P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34+ (P = 5.42 × 10-20) and CD34+CD38- MDS (P = 7.62 × 10-9) cells compared with normal CD34+ cells. MDS patients with higher FAK in CD34+ cells tended to have better overall survival (P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR.


[Determination of trace metals in atmospheric dry deposition with a heavy matrix of PUF by inductively coupled plasma mass spectroscopy after microwave digestion].
Interest in atmospheric dry deposition results mostly from concerns about the effects of the deposited trace elements entering waterbody, soil and vegetation as well as their subsequent health effects. A microwave assisted digestion method followed by inductively coupled plasma mass spectrometric (MAD-ICP/MS) analysis was developed to determine the concentrations of a large number of trace metals in atmospheric dry deposition samples with a heavy matrix of polyurethane foam (PUF). A combination of HNO3-H2O2-HF was used for digestion. The experimental protocol for the microwave assisted digestion was established using two different SRMs (GBW 07401, Soil and GBW 08401, Coal fly ash). Subsequently, blanks and limits of detection for total trace metal concentrations were determined for PUF filter which was used for dry deposition sampling. Finally, the optimized digestion method was applied to real world atmospheric dry deposition samples collected at 10 sites in Jingjinji area in winter from Dec. 2007 to Feb. 2008. The results showed that the area-averaged total mass fluxes ranged between 85 and 912 mg x (m2 x d)(-1), and fluxes of most elements were highest at Baoding and lowest at Xinglong. In addition, the elemental fluxes in urban areas of Beijing, Tianjin and Tangshan were measured to be higher than that in suburb and rural sites. The average fluxes of crust elements (A1, Fe, Mn, K, Na, Ca and Mg) were one to three orders of magnitude higher than anthropogenic elements (Cu, Pb, Cr, Ni, V, Zn and Ba), varying from 151 to 16034 microg x (m2 x d)(-1) versus 14 to 243 microg x (m2 x d)(-1). Zinc was the most abundant heavy metal and calcium the highest of the crust elements while the elements Mo, Co, Cd, As and Be deposited less or even could not be detected. The anthropogenic and crustal contributions were estimated by employing enrichment factors (EF) calculated relative to the average crustal composition. The EF values of all elements except Pb and Zn were below 10, suggesting that local soil and/or dust generally dominate in the dry deposition flux.


Enhanced haemodynamic effects of propranolol in acute myocardial infarction.
To evaluate the possible influence of sympathetic activation on the haemodynamic response to intravenous beta-blockade, the dose-response characteristics of three boluses of propranolol were evaluated in 8 patients with uncomplicated infarction and compared in a similar number of patients with stable angina. Following a control period, when haemodynamic stability was confirmed, propranolol 2, 2 and 4 mg (cumulative dosage 2, 4 and 8 mg) was injected into the central circulation at 15 min intervals. Despite close matching in baseline control haemodynamic variables between the groups, in stable angina, propranolol resulted in dose-related depression of cardiac output without change in systemic blood pressure, whereas following myocardial infarction the drug induced significantly greater falls in cardiac output (P less than 0.05) and a dose-related decrease in systemic blood pressure. Despite the greater effects of propranolol on cardiac output following myocardial infarction, the left ventricular filling pressure was increased to a lesser extent compared with stable angina. The explanation for this observation may reside in a greater susceptibility of the left ventricular wall to increase its compliance, under conditions of high sympathetic stimulation, following beta-blockade. These data support experimental and biochemical evidence of sympathetic activation in myocardial infarction; the hyperadrenergic state conditions an augmented haemodynamic response to competitive antagonism of sympathetic stimulation at cardiac beta-adrenoceptors.


Ultrastructural evidence of collagenolytic activity in ductal infiltrating carcinoma of the human breast.
The stroma of ductal infiltrating carcinoma of the human breast shows characteristic and localized areas of collagen rarefaction and fragmentation. This finding has been correlated with a peculiar type of fibrillar damage, observed in a small percentage of collagen fibrils isolated in the native state from the tumour stroma. The same pattern of lesion has been reproduced in vitro by human collagenase digestion on reconstituted fibrils. No effect has been detected by other nonspecific proteases in the same system.


Oral language and narrative skills in children with specific language impairment with and without literacy delay: a three-year longitudinal study.
This longitudinal study compared the development of oral language and more specifically narrative skills (storytelling and story retelling) in children with specific language impairment (SLI) with and without literacy delay. Therefore, 18 children with SLI and 18 matched controls with normal literacy were followed from the last year of kindergarten (mean age=5 years 5 months) until the beginning of grade 3 (mean age=8 years 1 month). Oral language tests measuring vocabulary, morphology, sentence and text comprehension and narrative skills were administered yearly. Based on first and third grade reading and spelling achievement, both groups were divided into a group with and a group without literacy problems. Results showed that the children with SLI and literacy delay had persistent oral language problems across all assessed language domains. The children with SLI and normal literacy skills scored also persistently low on vocabulary, morphology and story retelling skills. Only on listening comprehension and storytelling, they evolved towards the level of the control group. In conclusion, oral language skills in children with SLI and normal literacy skills remained in general poor, despite their intact literacy development during the first years of literacy instruction. Only for listening comprehension and storytelling, they improved, probably as a result of more print exposure.


Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival.
This study assessed whether putative effectors of phosphatidylinositol3-kinase, including PTEN, protein kinase B (PKB), and p27(kip1), correlate with each other, with glioma histology, and with patient outcome. Components of the phosphatidylinositol 3-kinase signaling cascade were characterized in 25 glioblastoma multiforme (GBM) tumors, 8 grade II oligoastrocytomas, and 13 normal human brain specimens. The protein levels of PTEN and p27(kip1) were assessed by immunoblot analyses. PKB kinase activity was evaluated through the expression level of the phosphorylated (activated) PKB protein and the ability of PKB to phosphorylate a specific peptide substrate in vitro. Cox regression analyses between expression/activity variables and survival were performed across and within histology types. Actual value for expression/activity was used as a continuous variable. Survival time was displayed by Kaplan Meier. A strong inverse correlation was evident between PTEN levels and both phosphorylated PKB expression (P < 0.01) and PKB activity (P = 0.01). p27(kip1) levels did not correlate with PTEN expression or PKB activity. A significant association was evident between PTEN expression level and histology (P < 0.01). PTEN levels were highest in normal brain, lowest in GBM tumors, and intermediate in grade II oligoastrocytomas. PKB activity and phosphorylated PKB levels differed significantly among histologies, whereas p27(kip1) levels exhibited no association with histology. PTEN expression correlated significantly with survival time within the entire cohort (P < 0.01) and was associated with survival within the subgroup of GBM tumors (P = 0.11). Reduced PTEN expression is ubiquitous among GBM tumors and may play a role in the development of low-grade gliomas. PTEN inactivation in gliomas portends a particularly aggressive clinical behavior.


Electrochemical nanostructuring of n-GaAs photoelectrodes.
Methods to simultaneously optimize carrier collection and light in-coupling in semiconductors are important for developing low-cost, high-efficiency photovoltaics and photoelectrodes. We anodically etched nanostructures into planar (100) n-GaAs wafers with different bulk minority carrier diffusion lengths L(D). The structures were varied by changing the anodization parameters. A ferrocene/ferrocenium electrolyte provided a conformal rectifying contact to the anodized n-GaAs and enabled the measurement of carrier generation and collection as a function of nanostructure geometry and L(D). Internal quantum efficiency Φ(int) of photoelectrodes varied with nanostructure geometry and L(D). External quantum efficiency Φ(ext) also depended on the reflectance of the nanostructured GaAs-electrolyte interface. Reflectance was minimized using anodization current densities of 100-150 mA cm(-2), which etched subwavelength trigonal prismatic nanostructures ~400 nm in width at their base. For Si-doped n-GaAs with L(D) = 170 nm, peak Φ(ext) of ~75% and Φ(int) of ~85% was achieved using J(anod) = 150 mA cm(-2). The control of both surface nanostructure (to minimize reflection) and pore depth and spacing (to optimize 3D carrier collection) via two-step anodization yielded photoelectrodes with peak Φ(ext) of ~85% and peak Φ(int) of ~95% for Te-doped n-GaAs with a bulk L(D) of only 420 nm. The measured short-circuit current densities for the nanostructured photoelectrodes were up to 2.5 times that of planar controls, demonstrating that appropriate nanostructuring significantly improves carrier collection even for direct bandgap materials with large absorption coefficients like GaAs.


A Novel Glycerol Kinase Gene OsNHO1 Regulates Resistance to Bacterial Blight and Blast Diseases in Rice.
Glycerol-induced resistance to various pathogens has been reported in different plants. Glycerol kinase (GK), a vital rate-limiting enzyme that catalyzes glycerol conversion to glycerol-3-phosphate (G3P), participates in responses to both abiotic and biotic stresses. However, its physiological importance in rice defenses against pathogens remains unclear. In this research, quantification analysis revealed that GK levels were significantly induced in rice leaves infected by Xanthomonas oryzae pv. oryzae (Xoo) strain PXO99. A typical GK-encoding gene OsNHO1 was cloned in rice. The transcriptional levels of OsNHO1 were significantly induced by salicylic acid, jasmonic acid, and Xoo-PXO99. Ectopic expression of OsNHO1 partially rescued the resistance to P. s. pv. phaseolicola in the Arabidopsis nho1 mutant. In the overexpressing transgenic rice lines (OsNHO1-OE), the content of GK and the transcriptional level of OsNHO1 were increased and the resistance to bacterial blight and blast was improved, while reduced OsNHO1 expression impaired the resistance in OsNHO1-RNAi lines. The wax contents and expression of the wax synthesis regulatory genes were significantly increased in the overexpression lines but decreased in the OsNHO1-RNAi lines. We then confirmed the interaction partner of OsNHO1 using yeast two-hybrid and bimolecular fluorescence complementation assays. The transcription of the interaction partner-encoding genes OsSRC2 and OsPRs in OsNHO1-RNAi lines was downregulated but upregulated in OsNHO1-OE lines. Thus, we concluded that OsNHO1 provided disease resistance by affecting the wax content and modulating the transcription levels of PR genes.


Phylogenetic analysis and recombination events in full genome sequences of apple stem grooving virus.
Apple stem grooving virus (ASGV) is one of the most important viral pathogens infecting pome and stone fruit trees worldwide. In this study, with the complete nucleotide sequence of isolate ASGV-T47, which we generated, molecular variation and recombination in ASGV full genomic sequences worldwide were analyzed. ASGV-T47 shared 79.7-97.6% nucleotide identity with the other isolates worldwide and had the highest identity with an isolate from Japan. Phylogenetic analysis based on whole genome clustered all 16 isolates from around the world into two groups with no correlation to host or geographical origin. Four isolates were detected to be recombinants. Selection pressure estimation indicated that the two codons at positions 1756 and 1798 are under positive selection, while purifying selection is the primary evolutionary dynamics for ASGV.