Dominant Negative Mutants of Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) Disrupt Core-Binding Factor Beta-Vif Interaction.
Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3s) are host restriction factors that inhibit viral replication. Viral infectivity factor (Vif), a human immunodeficiency virus type 1 (HIV-1) accessory protein, mediates the degradation of APOBEC3s by forming the Vif-E3 complex, in which core-binding factor beta (CBFβ) is an essential molecular chaperone. Here, we screened nonfunctional Vif mutants with high affinity for CBFβ to inhibit HIV-1 in a dominant negative manner. We applied the yeast surface display technology to express Vif random mutant libraries, and mutants showing high CBFβ affinity were screened using flow cytometry. Most of the screened Vif mutants containing random mutations of different frequencies were able to rescue APOBEC3G (A3G). In the subsequent screening, three of the mutants restricted HIV-1, recovered G-to-A hypermutation, and rescued APOBEC3s. Among them, Vif-6M showed a cross-protection effect toward APOBEC3C, APOBEC3F, and African green monkey A3G. Stable expression of Vif-6M in T lymphocytes inhibited the viral replication in newly HIV-1-infected cells and the chronically infected cell line H9/HXB2. Furthermore, the expression of Vif-6M provided a survival advantage to T lymphocytes infected with HIV-1. These results suggest that dominant negative Vif mutants acting on the Vif-CBFβ target potently restrict HIV-1. IMPORTANCE Antiviral therapy cannot eliminate HIV and exhibits disadvantages such as drug resistance and toxicity. Therefore, novel strategies for inhibiting viral replication in patients with HIV are urgently needed. APOBEC3s in host cells are able to inhibit viral replication but are antagonized by HIV-1 Vif-mediated degradation. Therefore, we screened nonfunctional Vif mutants with high affinity for CBFβ to compete with the wild-type Vif (wtVif) as a potential strategy to assist with HIV-1 treatment. Most screened mutants rescued the expression of A3G in the presence of wtVif, especially Vif-6M, which could protect various APOBEC3s and improve the incorporation of A3G into HIV-1 particles. Transduction of Vif-6M into T lymphocytes inhibited the replication of the newly infected virus and the chronically infected virus. These data suggest that Vif mutants targeting the Vif-CBFβ interaction may be promising in the development of a new AIDS therapeutic strategy.


[Venous drainage and innervation of the maxillary sinus].
The maxillary sinus, or "Highmore's antrum", is a cavity of the facial structure buried in the body of the maxillary body joined to the nasal fossae with which it communicates via the maxillary ostium. The dissection of 25 maxillary sinuses has enabled us to study its venous drainage and innervation. The venous system is collected either by a single trunk, which is a continuation of the spheno-palatine vein, or by three venous plexus: the anterior and posterior pterygoid plexus, and the alveolar plexus. The anterior and posterior pterygoid plexus converge through the lateral pterygoid muscle and connects with the alveolar plexus which drains partly into the maxillary vein and partly into the facial vein. The innervation of the maxillary sinus is ensured by the maxillary nerve (V2): the second branch of the trigeminal nerve and its collateral branches. During the course of its track the maxillary nerve becomes successively the spheno-palatine nerve and the anterior orbital nerve, and gives rise to some collateral branches: the posterior and superior alveolar ramus, the medium and superior alveolar nexus and the anterior and superior alveolar ramus.


Fostering adjustment to acquired brain injury by psychotherapeutic interventions: a preliminary study.
This preliminary study investigates the effectiveness of a treatment program in which neuropsychological interventions are supplemented by psychotherapeutic interventions to foster the adjustment process. Eleven patients who had an adjustment disorder following an acquired brain injury were recruited for the treatment group. Measures were assessed at the beginning and end using the Structured Clinical Interview, the Beck Depression Inventory, the Goal Attainment Scaling procedure, and the Trier Coping Scales. Significant pre- to post-assessment differences emerged in terms of depression and coping styles. The findings suggest that patients benefit from an integrated treatment program to foster adjustment. These findings encourage further investigation of this integrative treatment in larger samples through randomized controlled trials with adequate control treatments.


High-sensitivity and wide-temperature-range dual-mode optical thermometry under dual-wavelength excitation in a novel double perovskite tellurate oxide.
Novel double perovskite SrLaLiTeO6 (abbreviated as SLLT):Mn4+,Dy3+ phosphors synthesized using a solid-state reaction strategy exhibit distinct dual-emission of Mn4+ and Dy3+. High-sensitivity and wide-temperature-range dual-mode optical thermometry was exploited taking advantage of the diverse thermal quenching between Mn4+ and Dy3+ and the decay lifetime of Mn4+. The thermometric properties in the range of 298-673 K were investigated by utilizing the fluorescence intensity ratio (FIR) of Dy3+ (4F9/2→6H13/2)/Mn4+ (2Eg→4A2g) and the Mn4+ (2Eg→4A2g) lifetime under 351 nm and 453 nm excitation, respectively. The maximum relative sensitivities (SR) of the resultant SLLT:1.2%Mn4+,7%Dy3+ phosphor under 351 nm and 453 nm excitation employing the FIR technology were determined to be 1.60% K-1 at 673 K and 1.44% K-1 at 673 K, respectively. Additionally, the maximum SR values based on the lifetime-mode were 1.59% K-1 at 673 K and 2.18% K-1 at 673 K, respectively. It is noteworthy that the SR values can be manipulated by different excitation wavelengths and multi-modal optical thermometry. These results suggest that the SLLT:Mn4+,Dy3+ phosphor has prospective potential in optical thermometry and provide conducive guidance for designing high-sensitivity multi-modal optical thermometers.


High-cell-density fed-batch culture of Saccharomyces cerevisiae KV-25 using molasses and corn steep liquor.
High-cell-density cultivation of yeast was investigated using the agricultural waste products corn steep liquor (CSL) and molasses. The Saccharomyces cerevisiae KV-25 cell mass was significantly dependent on the ratio between C and N sources. The concentrations of molasses and CSL in the culture medium were statistically optimized at 10.25% (v/v) and 16.87% (v/v), respectively, by response surface methodology (RSM). Batch culture in a 5-l stirred tank reactor using the optimized medium resulted in a cell mass production of 36.5 g/l. In the fed-batch culture, the feed phase was preceded by a batch phase using the optimized medium, and a very high dried-cell-mass yield of 187.63 g/l was successfully attained by feeding a mixture of 20% (v/v) molasses and 80% (v/v) CSL at a rate of 22 ml/h. In this system, the production of cell mass depended mainly on the agitation speed, the composition of the feed medium, and the glucose level in the medium, but only slightly on the aeration rate.


An integrated structural intervention to reduce vulnerability to HIV and sexually transmitted infections among female sex workers in Karnataka state, south India.
Structural factors are known to affect individual risk and vulnerability to HIV. In the context of an HIV prevention programme for over 60,000 female sex workers (FSWs) in south India, we developed structural interventions involving policy makers, secondary stakeholders (police, government officials, lawyers, media) and primary stakeholders (FSWs themselves). The purpose of the interventions was to address context-specific factors (social inequity, violence and harassment, and stigma and discrimination) contributing to HIV vulnerability. We advocated with government authorities for HIV/AIDS as an economic, social and developmental issue, and solicited political leadership to embed HIV/AIDS issues throughout governmental programmes. We mobilised FSWs and appraised them of their legal rights, and worked with FSWs and people with HIV/AIDS to implement sensitization and awareness training for more than 175 government officials, 13,500 police and 950 journalists. Standardised, routine programme monitoring indicators on service provision, service uptake, and community activities were collected monthly from 18 districts in Karnataka between 2007 and 2009. Daily tracking of news articles concerning HIV/AIDS and FSWs was undertaken manually in selected districts between 2005 and 2008. The HIV prevention programme is now operating at scale, with over 60,000 FSWs regularly contacted by peer educators, and over 17,000 FSWs accessing project services for sexually transmitted infections monthly. FSW membership in community-based organisations has increased from 8,000 to 37,000, and over 46,000 FSWs have now been referred for government-sponsored social entitlements. FSWs were supported to redress > 90% of the 4,600 reported incidents of violence and harassment reported between 2007-2009, and monitoring of news stories has shown a 50% increase in the number of positive media reports on HIV/AIDS and FSWs. Stigma, discrimination, violence, harassment and social equity issues are critical concerns of FSWs. This report demonstrates that it is possible to address these broader structural factors as part of large-scale HIV prevention programming. Although assessing the impact of the various components of a structural intervention on reducing HIV vulnerability is difficult, addressing the broader structural factors contributing to FSW vulnerability is critical to enable these vulnerable women to become sufficiently empowered to adopt the safer sexual behaviours which are required to respond effectively to the HIV epidemic.


Eco-friendly hybrid pigments made of cellulose and iron oxides.
The controlled hydrolysis of FeC2O4 in the presence of vegetable cellulose fibres was investigated to produce a pallet of cellulose/iron oxide hybrid colored materials. Distinct iron oxide phases have been deposited at the cellulose fibres surfaces by varying the relative amount of FeC2O4 and NaOH, here used as starting materials, by performing the synthesis in hydrothermal conditions. This is a new chemical strategy for the production of a number of hybrid materials whose coloristic properties have been evaluated aiming their potential use as novel pigments for polymer based products.


[Subjective Workload, Job Satisfaction, and Work-Life-Balance of Physicians and Nurses in a Municipal Hospital in a Rural Area Compared to an Urban University Hospital].
Medical and nursing shortages in rural areas represent a current serious public health problem. The healthcare of the rural population is at risk. This study compares perceived workload, job satisfaction and work-life balance of physicians and nurses at a clinic in a rural area with two clinics of a University hospital. Physicians and nurses were interviewed anonymously with a standardized questionnaire (paper and pencil), including questions on job satisfaction, subjective workload and work-life balance. The response rate was almost 50% in the University hospital as well as in the municipal hospital. 32 physicians and 54 nurses from the University hospital and 18 physicians and 137 nurses from the municipal hospital participated in the survey. Nurses at the University hospital assessed the organization of the daily routine with 94.1% as better than those at the municipal hospital (82.4%, p=0.03). Physicians at the University hospital were able to better implement acquired knowledge at a University clinic with 87.5% than their counterparts at the municipal hospital (55.5%, p=0.02). In contrast to their colleagues at the municipal hospital, only 50% of the physicians at the University hospital subjectively considered their workload as just right (83.3% municipal, p=0.02). 96.9% of the physicians at the University hospital were "daily" or "several times a week" under time pressure (municipal 50%, p<0.01). Nurses of both hospitals had sufficient opportunity to reconcile work and family life (62.9% University hospital, 72.8% Municipal hospital). In contrast, only 20% of the physicians at the University Hospital but 42.9% of the physicians of the municipal hospital had sufficient opportunities to balance workload and family (p=0.13). The return rate of almost 50% can be described as good. Due to the small number of physicians, especially from the municipal hospital, it can be assumed that some interesting differences could not be detected. There were only slight differences between the nurses from the two hospitals. In contrast, subjective workload and stress factors reported by physicians at the University Hospital were significantly higher than those by doctors at the municipal hospital.


Worldwide regional variations in home advantage in association football.
Home advantage plays an important part in determining the result of a game of football. Its existence and magnitude is well documented in England, but its causes are still not completely understood. In this study, reliable estimates of home advantage are calculated for the domestic leagues of all countries of Europe and South America, as well as a selection of countries from other continents. The results of all games during the last six seasons are used for each of these 72 countries. In Europe, home advantage in the Balkan countries, especially Bosnia and Albania, is much higher than average. It is generally lower than average in northern Europe, from the Baltic republics, through Scandinavia to the British Isles. In South America, home advantage is high in the Andean countries and lower elsewhere, especially in Uruguay. Home advantage is not unusually high or low in any of the countries from other continents. A multiple regression model for the 51 European countries, which included variables for geographical location, crowd effects and travel, accounted for 76.7% of the variability in home advantage. The large geographical variations can be interpreted in terms of territoriality being a contributing factor to home advantage.


Cystic tumors of the pancreas: preoperative imaging, diagnosis, and treatment.
The objective of this retrospective study was to explore the accuracy of preoperative diagnostic methods and the efficacy of treatment for cystic pancreatic tumors. From 1989 to 1999, 18 patients underwent surgery for cystic tumor of the pancreas, classified as follows: one serous cystadenoma, eight mucinous cystadenomas, six mucinous cystadenocarcinomas, and three nonfunctioning islet cell tumors. Computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and fine needle aspiration were performed and subsequently reviewed retrospectively by two radiologists. Three patients underwent the Whipple procedure and 14 and 1 patients underwent distal and central pancreatectomy, respectively. CT showed cystic pancreatic tumors in all cases. One case was misdiagnosed as a pseudocyst. The diagnosis was accurate in 82%, 53%, 37%, and 60% of cases on CT, ERCP, and angiography, and in the cytologic analysis of the aspirated fluid, respectively. All operative procedures were performed without significant morbidity and there were no postoperative deaths. Preoperative diagnosis of cystic pancreatic tumours is imprecise. CT is the most reliable preoperative imaging method. Resection should be the treatment of choice for these lesions, except in cases of serous cystadenoma.


Ion beam sputtering nanopatterning of thin metal films: the synergism of kinetic self-organization and coarsening.
Creation of self-organized surface nanostructures by ion beam sputtering (IBS) has strong potential for use in a broad range of technologies, from nanoelectronics and photonics to sensing and catalysis. Recently, we have developed a simple two-stage process for fabricating self-assembled arrays of Cu dots and lines on Si and SiO(2) substrates employing IBS of thin Cu films. We found that the self-assembled structures on the substrate result from a complex interaction between the structure-forming kinetic instability and various outcomes of the surface diffusion and coarsening, which tend to drive the surface pattern towards a thermodynamic equilibrium. Here, we analyze in detail the interplay of the kinetic nanopatterning and coarsening, in order to better understand the mechanisms defining the IBS-generated metallic structures on substrates of a different material. By means of kinetic Monte Carlo (KMC) modeling we investigate the pertinent trends of the self-organization at the surface of a metallic film. In the light of this discussion, we review the fabricated nanostructures. Finally, we present a KMC model of the two-stage IBS process and analyze the stability of the fabricated metal patterns at the surface of a substrate. We discuss the opportunities and challenges of this technique, concluding that the IBS creation of surface heterostructures provides considerable room for future numerical and experimental studies.


Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty.
The local infiltration analgesia (LIA) technique has been widely used to reduce opioid requirements and to improve postoperative mobilization following total hip arthroplasty (THA). However, the evidence for the efficacy of LIA in THA is not yet clear. We determined whether single-shot LIA in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA. 116 patients undergoing primary THA under spinal anesthesia were included in this randomized, double-blind, placebo-controlled trial. All patients received oral opioid-sparing multimodal analgesia: etoricoxib, acetaminophen, and glucocorticoid. The patients were randomized to receive either 150 mL ropivacaine (2 mg/mL) and 0.5 mL epinephrine (1 mg/mL) or 150 mL 0.9% saline. Rescue analgesic consisted of morphine and oxycodone as needed. The primary endpoint was pain during mobilization in the recovery unit. Secondary endpoints were pain during mobilization on the day after surgery and total postoperative opioid requirements on the first postoperative day. The levels of pain during mobilization-both in the recovery unit and on the day after surgery-and consumption of opioids on the first postoperative day were similar in the 2 groups. LIA did not provide any extra analgesic effect after THA over and above that from the multimodal analgesic regimen used in this study.


A predominant pelvic gastrointestinal stromal tumor (GIST) mass observed on Tc-99m red blood cell gastrointestinal bleeding scintigraphy.
A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It demonstrated an apparent hypervascular pelvic mass, and active small bowel bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating tumor, CT of the abdomen and pelvis was performed for further gastrointestinal bleeding localization work up instead of an invasive angiography or endoscopy, which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal stromal tumor was resected subsequently.


Internal versus external fixation for unstable distal radius fractures: an up-to-date meta-analysis.
Our aim was to compare the effect of internal vs external fixation for unstable distal radius fractures regarding postoperative complications, clinical results and radiological outcomes. We selected PubMed; Cochrane Library; EMBASE; BIOSIS; Ovid and the relevant English orthopaedic journals and pooled data from ten eligible randomised controlled trials containing 738 patients to conduct a subgroup analysis according to different periods of follow-up. Our aim was to summarise the best available evidence. Results showed that compared with external fixation, internal fixation led to significantly fewer total surgical complications [95% confidence interval (CI) 0.39-0.81, P = 0.002] and reduced the incidence of pin-track infections (95% CI 0.08-0.46, P = 0.0002) after a one year follow-up. For clinical results, grip strength (95% CI 1.59-8.25, P = 0.004), supination (95% CI 13.99-48.83, P = 0.0004) and pronation (95% CI 5.61-26.09, P = 0.002) were superior in the internal fixation group six weeks postoperatively, and the same results were obtained three months postoperatively for grip strength (95% CI 3.21-13.47, P = 0.001) and supination (95% CI 3.61-16.01, P = 0.002). Meanwhile, the Disabilities of the Arm, Shoulder and Hand (DASH) score was superior in the internal fixation group at three months (95% CI -20.62 to -2.07, P = 0.02) and after one year (95% CI -14.37 to -2.32, P = 0.007) follow-up. We suggest that the final results are significant and there is some evidence supporting the use of open reduction and internal fixation.


Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods.
The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients' brains induce self-templated amplification and cell-to-cell transmission in vitro and in vivo. However, it is unclear whether exposure to exogenous prion-like proteins can potentially cause these diseases in humans. Here, we investigated in detail the prion-like seeding activities of several kinds of pathogenic α-synuclein (α-syn), including synthetic fibrils and detergent-insoluble fractions extracted from brains of patients with α-synucleinopathies. Exposure to synthetic α-syn fibrils at concentrations above 100 pg/mL caused seeded aggregation of α-syn in SH-SY5Y cells, and seeded aggregation was also observed in C57BL/6 J mice after intracerebral inoculation of at least 0.1 μg/animal. α-Syn aggregates extracted from brains of multiple system atrophy (MSA) patients showed higher seeding activity than those extracted from patients with dementia with Lewy bodies (DLB), and their potency was similar to that of synthetic α-syn fibrils. We also examined the effects of various methods that have been reported to inactivate abnormal prion proteins (PrPSc), including autoclaving at various temperatures, exposure to sodium dodecyl sulfate (SDS), and combined treatments. The combination of autoclaving and 1% SDS substantially reduced the seeding activities of synthetic α-syn fibrils and α-syn aggregates extracted from MSA brains. However, single treatment with 1% SDS or generally used sterilization conditions proved insufficient to prevent accumulation of pathological α-syn. In conclusion, α-syn aggregates derived from MSA patients showed a potent prion-like seeding activity, which could be efficiently reduced by combined use of SDS and autoclaving.


Judgement of discrete and continuous quantity in adults: number counts!
Three experiments involving a Stroop-like paradigm were conducted. In Experiment 1, adults received a number comparison task in which large sets of dots, orthogonally varying along a discrete dimension (number of dots) and a continuous dimension (cumulative area), were presented. Incongruent trials were processed more slowly and with less accuracy than congruent trials, suggesting that continuous dimensions such as cumulative area are automatically processed and integrated during a discrete quantity judgement task. Experiment 2, in which adults were asked to perform area comparison on the same stimuli, revealed the reciprocal interference from number on the continuous quantity judgements. Experiment 3, in which participants received both the number and area comparison tasks, confirmed the results of Experiments 1 and 2. Contrasting with earlier statements, the results support the view that number acts as a more salient cue than continuous dimensions in adults. Furthermore, the individual predisposition to automatically access approximate number representations was found to correlate significantly with adults' exact arithmetical skills.


The neurochemical circuitry of schizophrenia.
The aim of this paper is to describe the connectivity of some basic neuronal circuits assumed to be causally related to the generation of symptoms in schizophrenia. The role of various transmitter substances like dopamine, glutamate, serotonin and GABA can be explained by the circuitry of the respective pathways in the brain. Activating and inhibiting loops that are coupled can shift into an imbalance that might result in the generation of positive and negative symptoms. Finally, the paper draws attention to the hypothesis that extrasynaptic receptors might play an important role in schizophrenia. The paper shows that thinking in loops might be an efficient strategy for obtaining a functional understanding of the neuronal circuitry involved in the complex symptomatology of schizophrenia. Those models help us to understand the action of antipsychotic medications.


Multiparametric corticofugal modulation of collicular duration-tuned neurons: modulation in the amplitude domain.
The subcortical auditory nuclei contain not only neurons tuned to a specific frequency but also those tuned to multiple parameters characterizing a sound. All these neurons are potentially subject to modulation by descending fibers from the auditory cortex (corticofugal modulation). In the past, we electrically stimulated cortical duration-tuned neurons of the big brown bat, Eptesicus fuscus, and found that its collicular duration-tuned neurons were corticofugally modulated in the frequency and time (duration) domains. In the current paper, we report that they were also corticofugally modulated in the amplitude (intensity) domain. We found the following collicular changes evoked by focal cortical electric stimulation. 1) Corticofugal modulation in the amplitude domain differed depending on whether recorded collicular neurons matched in best frequency (BF) with stimulated cortical neurons. BF-matched neurons decreased their thresholds, whereas BF-unmatched neurons increased their thresholds: the larger the BF difference between the recorded collicular and stimulated cortical neurons, the larger the threshold increase. 2) In general, the dynamic range for amplitude coding was larger in the inferior colliculus than in the auditory cortex. BF-matched neurons increased their dynamic ranges and response magnitude, whereas BF-unmatched neurons decreased them. 3) Single duration-tuned neurons were simultaneously modulated by cortical electric stimulation in the amplitude, frequency and time domains. 4) Corticofugal modulation in these three domains indicates that the contrast of the neural representation of repeatedly delivered sound stimuli is increased.


C-terminal proteolysis of the collagen VI α3 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes.
The assembly of collagen VI microfibrils is a multistep process in which proteolytic processing within the C-terminal globular region of the collagen VI α3 chain plays a major role. However, the mechanisms involved remain elusive. Moreover, C5, the short and most C-terminal domain of the α3 chain, recently has been proposed to be released as an adipokine that enhances tumor progression, fibrosis, inflammation, and insulin resistance and has been named "endotrophin." Serum endotrophin could be a useful biomarker to monitor the progression of such disorders as chronic obstructive pulmonary disease, systemic sclerosis, and kidney diseases. Here, using biochemical and isotopic MS-based analyses, we found that the extracellular metalloproteinase bone morphogenetic protein 1 (BMP-1) is involved in endotrophin release and determined the exact BMP-1 cleavage site. Moreover, we provide evidence that several endotrophin-containing fragments are present in various tissues and body fluids. Among these, a large C2-C5 fragment, which contained endotrophin, was released by furin-like proprotein convertase cleavage. By using immunofluorescence microscopy and EM, we also demonstrate that these proteolytic maturations occur after secretion of collagen VI tetramers and during microfibril assembly. Differential localization of N- and C-terminal regions of the collagen VI α3 chain revealed that cleavage products are deposited in tissue and cell cultures. The detailed information on the processing of the collagen VI α3 chain reported here provides a basis for unraveling the function of endotrophin (C5) and larger endotrophin-containing fragments and for refining their use as biomarkers of disease progression.


[The necessary conditions of chronic total occlusion of all three coronary vessels--the relationship between portions of coronary occlusion and collateral vessels].
This study was performed to define the conditions present in chronic total occlusion of all three coronary vessels. Each left descending coronary artery (LAD), left circumflex branch (LCX) and right coronary artery (RCA) was totally occluded angiographically in 5 patients (mean age 64, male 3, female 2). Four of them had history of myocardial infarction. Anginal type was effort angina in all patients, and two cases showed unstable angina. Good collateral supply was found in the distal portions of occluded vessels from proximally located branches, such as Conus branch, Right ventricular branch, Septal branch and Left atrial circumflex branch. Almost all of the occlusions were located at mid portions (13/15: mid, 2/15: proximal). Ejection fractions (EF%) of the 5 patients were 70%, 69%, 60%, 28% and 22% respectively. EF was correlated with the degree of collateral supply and one of them (22%) ended in sudden death. These findings suggest that the mid portion occlusion, good collateral supply and a long history of angina pectoris are important factors involved in chronic total occlusion of the three coronary vessels.


[Decentralizing review sessions for patients who have undergone an oral anticoagulant treatment].
Therapeutic use of oral anticoagulants began some fifty years ago. In the past decade, we have witnessed a large increase in the number of people who undergo oral anticoagulant treatment. A correct applied control on these patients, whether that control be carried out in a hospital setting or in a primary health care center, has been demonstrated to be effective in preventing serious complications; this fact taken into account with the improved life quality gained by avoiding displacements and inconveniences makes it obvious to conclude that decentralization benefits all concerned. There are various models available to use to manage oral anticoagulant treatment. In this analysis, the authors deal with the management carried out from a primary health care center which contacts patients after their dosis has been adjusted and validated by a hematologist at the Torrecárdenas Hospital Complex. As their hypothesis, the authors of this study plan to demonstrate the possibility of decentralizing the reviews of patients undergoing oral anticoagulant treatment, thereby avoiding trips in order to control and adjust their treatment. This is a non-random clinical study whose study group has been chosen by means of a non-probability criteria. This study lasted 12 months. The subjects were chosen from patients undergoing oral anticoagulant treatment registered in the hematology service's data base at the Torrecárdenas Hospital Complex in Almeria. Applied protocol for being included in this study was decentralization of coagulation. The study sample included 38,097 patients. This study included commentaries by the patients receiving this treatment as a fundamental element to prove its effectiveness.


Potential macro-detritivore range expansion into the subarctic stimulates litter decomposition: a new positive feedback mechanism to climate change?
As a result of low decomposition rates, high-latitude ecosystems store large amounts of carbon. Litter decomposition in these ecosystems is constrained by harsh abiotic conditions, but also by the absence of macro-detritivores. We have studied the potential effects of their climate change-driven northward range expansion on the decomposition of two contrasting subarctic litter types. Litter of Alnus incana and Betula pubescens was incubated in microcosms together with monocultures and all possible combinations of three functionally different macro-detritivores (the earthworm Lumbricus rubellus, isopod Oniscus asellus, and millipede Julus scandinavius). Our results show that these macro-detritivores stimulated decomposition, especially of the high-quality A. incana litter and that the macro-detritivores tested differed in their decomposition-stimulating effects, with earthworms having the largest influence. Decomposition processes increased with increasing number of macro-detritivore species, and positive net diveristy effects occurred in several macro-detritivore treatments. However, after correction for macro-detritivore biomass, all interspecific differences in macro-detritivore effects, as well as the positive effects of species number on subarctic litter decomposition disappeared. The net diversity effects also appeared to be driven by variation in biomass, with a possible exception of net diversity effects in mass loss. Based on these results, we conclude that the expected climate change-induced range expansion of macro-detritivores into subarctic regions is likely to result in accelerated decomposition rates. Our results also indicate that the magnitude of macro-detritivore effects on subarctic decomposition will mainly depend on macro-detritivore biomass, rather than on macro-detritivore species number or identity.


Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus.
Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.


Intestinal and multivisceral transplantation in children.
To describe a single-center experience of pediatric intestinal transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. Pediatric Itx presents multiple challenges because of the very young ages at which patients require transplantation and their higher susceptibility to infectious complications. We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), multivisceral (n = 61), and multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for multivisceral transplantation were expanded, and induction with Campath-1H was introduced. Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-1H, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant > or =1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.


Bioactivity and Bioaccessibility of Bioactive Compounds in Gastrointestinal Digestion of Tomato Bagasse Extracts.
A nutrient-rich diet is a key to improving the chemical signals, such as antioxidants, which modulate pathogens' resistance in the gut and prevent diseases. A current industrial problem is the generation of undervalued by-products, such as tomato bagasse, which are rich in bioactive compounds and of commercial interest (carotenoids and phenolic compounds). This work analyzed the effect of gastrointestinal digestion on the bioactivity and bioaccessibility of carotenoids and phenolic compounds from tomato bagasse extracts. Thus, the extraction by ohmic heating (OH) technology was compared with conventional (organic solvents). The results showed that the main phenolic compounds identified by UPLC-qTOF-MS were p-coumaric acid, naringenin, and luteolin. A higher recovery index for total phenolic compounds throughout the gastrointestinal digestion was observed for OH while for carotenoids, a strong reduction after stomach conditions was observed for both extracts. Furthermore, colon-available fraction exhibited a prebiotic effect upon different Bifidobacterium and Lactobacillus, but a strain-dependent and more accentuated effect on OH. Thus, the extraction technology highly influenced bioaccessibility, with OH demonstrating a positive impact on the recovery of bioactive compounds and related health benefits, such as antioxidant, anti-hypertensive, prebiotic, and anti-inflammatory properties. Of these properties, the last is demonstrated here for the first time.


Propranolol selectively blocks the enhanced parietal old/new effect during long-term recollection of unpleasant pictures: a high density ERP study.
Evidence from both animal and human research suggests that the formation of emotional memories is triggered by the beta-adrenergic system. To confirm whether modulation of central beta-adrenergic transmission is specifically involved in the neural signature of memory performance, the pre-encoding effect of propranolol (80 mg) on event-related potentials (ERPs) was measured in a placebo-controlled, double-blind, parallel-group study in 46 male healthy subjects using high density EEG and source imaging analysis during encoding and retrieval (after 1 week) of IAPS pictures of unpleasant, neutral and pleasant contents; for recognition 90 old pictures were randomly mixed with 90 new pictures. During retrieval correctly remembered old pictures elicited a significantly larger positive voltage change over the centro-parietal cortex than new pictures. Propranolol significantly reduced this old/new difference of the mean ERP amplitudes (500-800 ms) for unpleasant but not for neutral and pleasant memories. This effect correlated with salivary alpha-amylase activity, a surrogate for central adrenergic stimulation. In conclusion, propranolol selectively blocked the neural signature of unpleasant memories by mechanisms in which the parietal cortex seems to be specifically involved.


Mortality data in the age of drones ‡.
Mortality data plays an essential role in shaping humanitarian, legal and ethical responses to conflict situations. The rise of drone warfare poses new questions regarding the accuracy and reliability of mortality data in conflict. This article examines some of the methodological and political challenges to collecting mortality data in drone warfare, and how the way in which drones are framed in public discourse contributes to these challenges.


[Anti Pseudomonas aeruginosa antibiotic therapy in cystic fibrosis (exclusion of macrolides)].
Antibiotherapy is one of the main treatment in cystic fibrosis. Pseudomonas aeruginosa infection is one of the main causes of pulmonary degradation. The chronic sputum colonisation is characterized by the emergence of the mucoid phenotype, the formation of biofilm and the induction of excessive inflammatory response and consecutive tissue lesion. The choice of antibiotics depends on quantitative and qualitative analysis of sputum, bacteria resistance phenotypes and severity of infection. Treatment of P. aeruginosa is different in case of first colonization or chronic infection. In the first case, parenteral antibiotherapy (beta-lactams-aminoglycosids) followed by inhaled antibiotherapy may eradicate the germ. In the other case, superinfections can be treated with parenteral biantibiothérapy (beta-lactams or quinolons and aminoglycosides) during 15 to 21 days. This is associated with a better nutritional and respiratory status and a prolonged survival. Inhaled antibiotics between the courses have decreased the number of superinfections. This prolonged antibiotherapy must be monitored because of possible induction of bacterial resistance, nephrotoxicity and ototoxicity of aminosids and allergy to beta-lactams.


Research on the Optimal Allocation of Ecological Land from the Perspective of Human Needs-Taking Hechi City, Guangxi as an Example.
The configuration of ecological land directly affects the structure and function of an ecosystem and, ultimately, its ability to meet human needs. From the perspective of human needs, this paper classified human needs into material needs, security needs and spiritual needs. Using Hechi City, Guangxi as the study area, we combined the Multi-objective planning (MOP) and PLUS models to study the quantity and spatial optimization of ecological land under different human needs scenarios, and the optimal allocation of ecological land within the ecological red line was also discussed. We conclude that: (1) Hechi City currently has less arable land, which cannot fully guarantee the material needs of human beings; there is more forest land than the amount needed to meet human needs, which reduces the efficiency of ecological land use. (2) In terms of quantity optimization, and considering the goals of different human needs, the area of grass to forest should be extended to satisfy security needs; the area of arable land should be significantly increased in line with material needs; the area of grass and water, with the goal of accommodating spiritual needs, is the largest compared with the rest of the goals. Under the comprehensive needs goal, the forest land area is greatly reduced, and the rest of the land area is increased; the goals of human material, spiritual and security needs are basically met. (3) In terms of spatial layout optimization, in order to meet the security needs target, grass to forest conversion should be carried out in the northern area to enhance the aggregation of forest land; to meet the material needs target, the southwestern gentle slope area should be concentrated toward continuous farming to guarantee the aggregation of arable land while increasing the area of arable land; to meet the spiritual needs target, the area of water in the northwestern area should be increased, and the rest of the changes are similar to the security needs target; to meet the comprehensive needs target, the overall land use connectivity becomes stronger, the fragmented land types become less and the concentrated continuous area of forest land, arable land and grass increases. (4) The results of the ecological land adjustment within the ecological red line indicate that the current ecological red line delineation is good, and a small amount of adjustment can meet human needs. Based on human demand, combined with the MOP-PLUS model for ecological land optimization, it can accurately portray the spatial and temporal evolution pattern of land use and reveal the optimization path of ecological land, which has important theoretical and practical values.


Binding of zinc and calcium to inositol phosphates (phytate) in vitro.
Inositol compounds with three to five phosphate groups (IP3-IP5) were produced by hydrolysis of phytate (inositol hexaphosphate, IP6) and their binding affinities for calcium and zinc investigated at neutral pH with relative concentrations that had been found in a range of students' meals. Zn solubility was negligible at many of these concentrations, with less Zn bound to precipitates of Ca-IP6 than Ca-IP5. The capacity to precipitate Zn at these ratios fell between IP5 and IP3. Zn was partially desorbed by soluble chelators (histidine and picolinate), especially when it had been adsorbed to preformed Ca-IP precipitates. A lower proportion of Zn was accessible to soluble chelators from Ca-IP4 than the other compounds. IP3-IP4 were hydrolysed by phytase more readily than IP5-IP6.


In situ scanning tunnelling spectroscopy of inorganic transition metal complexes.
Redox molecules with equilibrium potentials suitable for electrochemical control offer perspectives in nanoscale and single-molecule electronics. This applies to molecular but also towards higher sophistication such as transistor or diode function. Most recent nanoscale or single-molecule functional systems are, however, fraught with operational limitations such as cryogenic temperatures and ultra-high vacuum, or lack of electrochemical potential control. We report here cyclic voltammetry (CV) using single-crystal Au(111)- and Pt(111)-electrodes and electrochemical in situ scanning tunnelling microscopy (STM) of a class of Os(II)/(III)- and Co(II)/(III)-complexes, the former novel molecular electronics. The complexes are robust, with ligand groups suitable for linking the complexes to the Au(111)- and Pt(111)-surfaces via N- and S-donor atoms. The data reflect monolayer behaviour. Interfacial ET of the Os-complexes is fast, kET(0) > or = 10(6) s(-1), while the Co-complex reacts much more slowly, kET(0) approximately (1-3) x 10(3) s(-1). In STM of the Os-complexes shows a maximum in the tunnelling current/overpotential relation at constant bias voltage with up to 50-fold current rise. The peak position systematically the bias voltage and equilibrium potential, in keeping with theoretical frames for two-step electron transfer (ET) of in situ STM of redox molecules. The molecular conductivity behaves broadly similarly. The Co-complex also shows a tunnelling spectroscopic feature but much weaker than the Os-complexes. This can be ascribed much smaller interfacial ET rate constant, again caused by large intramolecular nuclear reorganization and weak electronic coupling to the substrate electrode. Overall the has mapped the properties of target molecules needed for stable electronic switching, possible importance in molecular electronics towards the single-molecule level, in room temperature condensed matter environment.


Health characteristics by occupation and industry of longest employment.
Includes estimates on length of longest job held, limitation of activity, disability days, incidence of acute conditions, persons injured, hospitalizations, and utilization of medical and dental services of persons aged 17 years and over in the civilian noninstitutionalized population. These estimates are presented by occupation and industry of longest employment for those who had ever worked. Estimates are based on data collected in the National Health Interview Survey of 1980.


The Minimalist Program and the Origin of Language: A View From Paleoanthropology.
In arguing that articulate language is underpinned by an algorithmically simple neural operation, the Minimalist Program (MP) retrodicts that language emerged in a short-term event. Because spoken language leaves no physical traces, its ancient use must be inferred from archeological proxies. These strongly suggest that modern symbolic human behavior patterns - and, by extension, cognition - emerged both abruptly and late in time (subsequent to the appearance of Homo sapiens as an anatomical entity some 200 thousand years kyr ago). Because the evidence is compelling that language is an integral component of modern symbolic thought, the archeological evidence clearly supports the basic tenet of the MP. But the associated proposition, that language was externalized in an independent event that followed its initial appearance as a conduit to internal thought, is much more debatable.


Reciprocal isomerization of butyrate and isobutyrate by the strictly anaerobic bacterium strain WoG13 and methanogenic isobutyrate degradation by a defined triculture.
Isomerization of butyrate and isobutyrate was investigated with the recently isolated strictly anaerobic bacterium strain WoG13 which ferments glutarate to butyrate, isobutyrate, CO(2), and small amounts of acetate. Dense cell suspensions converted butyrate to isobutyrate and isobutyrate to butyrate. C-nuclear magnetic resonance experiments proved that this isomerization was accomplished by migration of the carboxyl group to the adjacent carbon atom. In cell extracts, both butyrate and isobutyrate were activated to their coenzyme A (CoA) esters by acyl-CoA:acetate CoA-transferases. The reciprocal rearrangement of butyryl-CoA and isobutyryl-CoA was catalyzed by a butyryl-CoA:isobutyryl-CoA mutase which depended strictly on the presence of coenzyme B(12). Isobutyrate was completely degraded via butyrate to acetate and methane by a defined triculture of strain WoG13, Syntrophomonas wolfei, and Methanospirillum hungatei.


The interlayer coupling modulation of a g-C3N4/WTe2 heterostructure for solar cell applications.
Constructing van der Waals (vdW) heterostructures has been proved to be an excellent strategy to design or modulate the physical and chemical properties of 2D materials. Here, we investigated the electronic structures and solar cell performances of the g-C3N4/WTe2 heterostructure via first-principles calculations. It is highlighted that the g-C3N4/WTe2 heterostructure presents a type-II band edge alignment with a band gap of 1.24 eV and a corresponding visible light absorption coefficient of ∼106 cm-1 scale. Interestingly, the band gap of the g-C3N4/WTe2 heterostructure could increase to 1.44 eV by enlarging the vdW gap to harvest more visible light energy. It is worth noting that the decreased band alignment difference resulting from tuning the vdW gap, leads to a promotion of the power conversion efficiency up to 17.68%. This work may provide theoretical insights into g-C3N4/WTe2 heterostructure-based next-generation solar cells, as well as a guide for tuning properties of vdW heterostructures.


Comparison Between the Pouch-Perineum Distance in Neonates With a Low-Type Anorectal Malformation With and Without an Opened Fistula: Pitfall of Measuring the Pouch-Perineum Distance on Sonography.
An anorectal malformation (ARM) in neonates requires urgent surgery, with the type of surgery being dependent on the type of malformation (low, intermediate, or high). Distal rectal pouch and perineum (pouch-perineum) distance is reported to be useful for differentiating the type of ARM; however, the impact of an opened fistula on pouch-perineum distance is not well known. The purpose of this study was to evaluate the difference in pouch-perineum distance between neonates with a low-type ARM with and without an opened fistula. We included 24 neonates with low-type ARM who underwent sonography before surgery. Eight neonates already had an opened fistula before sonography, and 16 did not. The pouch-perineum distance was measured using the perineal approach. Mann-Whitney U and Spearman's correlation coefficient tests were used for statistical analysis. The mean pouch-perineum distance in all neonates with a low-type ARM was 8.3 ± 2.9 mm. The pouch-perineum distance was substantially longer for an ARM with than without an opened fistula (10.6 ± 3.4 mm vs. 7.1 ± 1.7 mm; P = .02). No appreciable correlation was identified between the pouch-perineum distance and the postnatal day of examination (ρ = -.23, P = .26) or birth weight (ρ = .15, P = .47). The pouch-perineum distance is substantially longer in neonates with an ARM with an opened fistula than in those without an opened fistula. Caution should be exercised by the sonographic examiner in evaluating pouch-perineum distance in neonates with an opened fistula to prevent an incorrect surgical procedure based on misdiagnosis of the type of ARM.


Metabolism of the carbocyclic analogue of (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells. Incorporation of C-IVDU into DNA.
The carbocyclic analogues of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), in which the sugar moiety is replaced by a cyclopentane ring and which have been designated as C-BVDU and C-IVDU, respectively, are, like their parent compounds BVDU and IVDU, potent and selective inhibitors of herpes simplex virus type 1 (HSV-1) and, to a lesser extent, herpes simplex virus type 2 (HSV-2) replication. We have now synthesized the radiolabeled C-IVDU analogue, C-[125I]IVDU, and determined its metabolism by HSV-infected and mock-infected Vero cells. C-[125I]IVDU was effectively phosphorylated by HSV-1-infected cells and, to a lesser extent, HSV-2-infected cells. C-[125I]IVDU was not phosphorylated to an appreciable extent by either mock-infected cells or cells that had been infected with a thymidine kinase-deficient mutant of HSV-1. Furthermore, C-[125I]IVDU was incorporated into both viral and cellular DNA of HSV-1-infected Vero cells. This finding represents the first demonstration of the incorporation of a cyclopentylpyrimidine into DNA.


Stereoselective Synthesis of Nitrogen-Containing Compounds from Enamines.
The domino reaction of enamines, electrophiles (N-sulfonylimines, N-tosylisocyanate, or diethyl azodicarboxylate), and trichlorosilane provided trans-amines (trans/cis = > 99:1 to 96:4). Meanwhile, the sequential imino ene-type reaction of enamines and electrophiles/NaBH3CN reduction afforded cis-amines (trans/cis = 1:>99 to 15:85). The reversal of selectivity is discussed on the basis of diastereofacial selection of the plausible iminium ion intermediates. For the domino reaction of cyclic enamines and cyclic imines, high enantioselectivity (er = 95.7:4.3 to 99.9:0.1) was achieved by utilizing chiral Lewis base catalysts.


Cytotoxic and partial hepatoprotective activity of sodium ascorbate against hepatocellular carcinoma through inhibition of sulfatase-2 in vivo and in vitro.
Hepatocellular carcinoma (HCC) is characterized by elevation in the activity of sulfatase-2, an extracellular enzyme that catalyzes removal of 6-O-sulfate groups from heparan sulfate. Therefore, we conducted this study to investigate the cytotoxic activity of the strong water-soluble antioxidant, sodium ascorbate, against HCC both in vivo and in vitro. Sodium ascorbate enhanced animal survival in vivo and reduced HepG2 cells survival. The protein levels of heparan sulfate proteoglycans (HSPGs), insulin like growth factor (IGF)-2, sulfatase-2 and glypican-3 were assessed. Inflammation was evaluated by measuring the gene and protein expression of NFκB, TNF-α, IL-1β, IL-4, IL-6 and IL-10. We found that sodium ascorbate blocked HCC-induced activation of sulfatase-2 leading to restoration of HSPGs receptors associated with reduction in IGF-2 and glypican-3. Sodium ascorbate exerts anti-inflammatory activity by reducing the expression of NFκB, CRP, TNF-α, IL-1β and IL-6 associated with enhanced expression of the anti-inflammatory cytokines, IL-4 and IL-10. In conclusion, cytotoxic effects of sodium ascorbate against HCC can be partially explained by inhibition of sulfatase-2, restoration of HSPGs receptors and deactivation of the inflammatory pathway.


[Surgery of burns].
The surgical treatment of burns must provide the best conditions that assure re-epidermalisation of the burn. Two imperatives must be respected during the initial management: encourage rapid scarring of the burn as the loss of the protection of the cutaneous barrier leads to a significant risk of contamination of the burn and of generalised infection, and the quality of the burn scar (minimal retraction or hypertrophic reaction) is directly related to the duration of the scarring process; utilisation of the technique that will give the best aesthetic and functional results in treating firstly the exposed zones (face and hands) and the functional zones (flexural folds, articular regions). The surgical treatment should respect the areas that can spontaneously re-epidermalise (superficial or intermediate burns), however in the deeper lesions (second-degree or third-degree burns) the destruction of the basal layer capable of providing keratinisation and re-epidermalisation renders the recourse to skin transplantation indispensable, which must be performed before the fifteenth day in order to best avoid complications.


Fluorescent identification and detection of Staphylococcus aureus with carboxymethyl chitosan/CdS quantum dots bioconjugates.
A fast and sensitive method based on fluorescent carboxymethyl chitosan/CdS quantum dots (CMCS-CdS QDs) composites was developed for specific detection of Staphylococcus aureus in food and the environment. Fluorescent CMCS-CdS QDs were prepared in aqueous solution through a green method. A human immunoglobulin (IgG) antibody was then bioconjugated to the QDs in the presence of 1-ethyl-3-(3)-dimethylaminopropyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to make a novel type of mono-dispersed water-soluble fluorescent bioprobes. The fluorescent bioprobes were employed to identify S. aureus by incubating them with the bacteria for a certain time and observing the marked cells under fluorescence microscopy after removing free fluorescent QDs. Fluorescence microscopy images showed the S. aureus cells were successfully recognized by the bioprobes. Several other bacteria commonly found in environment such as Escherichia coli and Bacillus subtilis were also incubated with the bioprobes to test their specificity. It was found that the novel QDs-CMCS-IgG bioprobes had specific identification to S. aureus cells. Fluorescence measurement using a luminescence spectrometer could be applied to quantify S. aureus cells. The fluorescence intensity of the samples at 600 nm was proportional to the cell concentration in the range of 10(3)-10(7) cfu/ml, and the detection limit was as low as 900 cfu/ml. Considering the simplicity and cost-efficiency of this method, its application in the identification and quantification of bacteria in clinical, food and environmental samples is anticipated.


Is it possible to increase the diagnostic value of exercise electrocardiography by post-exercise B-type natriuretic peptide levels?
Exercise electrocardiography is commonly available and a cost-effective test and therefore is widely used for the diagnosis of coronary artery disease. However, false positivity remains an important problem resulting in many unnecessary coronary angiographic examinations. In this study, we aimed to test the hypothesis that post-exercise B-type natriuretic peptides secreted in response to transient myocardial ischaemia induced by exercise, add any further information on positive test results. Patients who underwent exercise electrocardiography with the suspicion of coronary artery disease were screened and those with positive test results based on standard electrocardiography criteria were selected. Blood samples for B-type natriuretic peptides were obtained within 5 minutes after exercise test. Patients included in the study had preserved left ventricular function on echocardiography. At least 70% stenosis of one epicardial coronary artery on coronary angiography was diagnosed as significant coronary artery disease. Of the 55 patients (age 59.8 +/- 7.6 y; 48 men) included in the study 29 had (52.7%) coronary artery disease requiring revascularization (CAD+) and 26 (47.3%) did not have significant coronary artery disease (CAD-). The cardiovascular risk factor profile of CAD+ and CAD- patients were similar (all p > 0.05). The median post-exercise B-type natriuretic peptide level was significantly higher in CAD+ (47.20 pg/ml) than CAD- patients (18.90 pg/ml) (P = 0.001). The sensitivity and specificity of a post-exercise B-type natriuretic peptide level > 30 pg/ml for the diagnosis of coronary artery disease in exercise test positive patients were calculated as 72% and 69%, respectively. The measurement of post-exercise B-type natriuretic peptide levels may increase the diagnostic value of positive exercise electrocardiography.


Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2.
Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.


Consecutive Supramolecular Polymerization of a Rylene-Based Twistacene.
The synthesis and self-assembling features of twistacene 1 are reported. The supramolecular polymerization of 1 displays a consecutive pathway to afford slipped (AggI) and rotationally displaced (AggII) aggregates conditioned by the formation of intramolecularly H-bonded pseudocycles. In methylcyclohexane, both AggI and AggII are highly stable and the interconversion of the kinetically controlled AggI into the thermodynamically controlled AggII takes several weeks to occur. The utilization of toluene as solvent changes the energetic level for both aggregates and favors a faster conversion of AggI into AggII within a period of minutes. This conversion can be accelerated by the addition of seeds. Furthermore, concentration dependent kinetic studies demonstrate the consecutive character of the supramolecular polymerization of 1.


Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes after the emergence of Omicron: A population-based cross-sectional study.
Inequities in Coronavirus Disease 2019 (COVID-19) vaccine and booster coverage may contribute to future disparities in morbidity and mortality within and between Massachusetts (MA) communities. We conducted a population-based cross-sectional study of primary series vaccination and booster coverage 18 months into the general population vaccine rollout. We obtained public-use data on residents vaccinated and boosted by ZIP code (and by age group: 5 to 19, 20 to 39, 40 to 64, 65+) from MA Department of Public Health, as of October 10, 2022. We constructed population denominators for postal ZIP codes by aggregating census tract population estimates from the 2015-2019 American Community Survey. We excluded nonresidential ZIP codes and the smallest ZIP codes containing 1% of the state's population. We mapped variation in ZIP code-level primary series vaccine and booster coverage and used regression models to evaluate the association of these measures with ZIP code-level socioeconomic and demographic characteristics. Because age is strongly associated with COVID-19 severity and vaccine access/uptake, we assessed whether observed socioeconomic and racial/ethnic inequities persisted after adjusting for age composition and plotted age-specific vaccine and booster coverage by deciles of ZIP code characteristics. We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups. In multivariable regression models, each 10 percentage point increase in "percent college educated" was associated with a 5.1 (95% confidence interval (CI) 3.9 to 6.3, p < 0.001) percentage point increase in primary series vaccine coverage and a 5.4 (95% CI 4.5 to 6.4, p < 0.001) percentage point increase in booster coverage. Although ZIP codes with higher "percent Black/Latino/Indigenous" and higher "percent essential workers" had lower vaccine coverage (-0.8, 95% CI -1.3 to -0.3, p < 0.01; -5.5, 95% CI -7.3 to -3.8, p < 0.001), these associations became strongly positive after adjusting for age and education (1.9, 95% CI 1.0 to 2.8, p < 0.001; 4.8, 95% CI 2.6 to 7.1, p < 0.001), consistent with high demand for vaccines among Black/Latino/Indigenous and essential worker populations within age and education groups. Strong positive associations between "median household income" and vaccination were attenuated after adjusting for age. Limitations of the study include imprecision of the estimated population denominators, lack of individual-level sociodemographic data, and potential for residential ZIP code misreporting in vaccination data. Eighteen months into MA's general population vaccine rollout, there remained large inequities in COVID-19 primary series vaccine and booster coverage across MA ZIP codes, particularly among younger age groups. Disparities in vaccination coverage by racial/ethnic composition were statistically explained by differences in age and education levels, which may mediate the effects of structural racism on vaccine uptake. Efforts to increase booster coverage are needed to limit future socioeconomic and racial/ethnic disparities in COVID-19 morbidity and mortality.


Functional properties of donor- and acceptor-co-doped high dielectric constant zinc oxide ceramics.
In this work we investigated the functional properties of a set of acceptor (Cu1+) and donor (Gd3+) codoped wurtzite ZnO ceramics Zn(1-x)(CuzGdy)xO for x = 0.01 synthesized by the pressure-less solid state sintering method. XRD and optical measurements established the substitution of dopant ions into zinc lattice sites directly. The co-doping process influenced the creation of oxygen vacancies which modified their electronic properties and decreased the band gap energy. The existence of such defects leads to non-radiative decay, which caused different electronic recombination in the luminescence emission. The samples exhibited a high dielectric constant (>= ∼103) with an acceptable low dielectric loss (tan δ ∼ 10-1) in the frequency range 10-103 Hz. The dielectric results were discussed in terms of different polarization effects that may be present in the lattice such as polaron-like electron transport/hopping, defect dipoles, and barrier layer capacitance effects. The presence of both donor (Gd3+) and acceptor (Cu1+) ions in ZnO decreased the dielectric loss in the materials and the most favorable balance between high dielectric constant and low dielectric loss properties was found. Impedance analysis ruled out any contribution from electrode-grain interfaces to the high-K (high dielectric constant) properties in pure and doped zinc oxide ceramics. The correlation between the physical properties studies are a guideline in the classificatory understanding of semiconductor materials.


Roles of oxidative stress, apoptosis, and heme oxygenase-1 in ethylbenzene-induced renal toxicity in NRK-52E cells.
Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 µmol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity.


Levodopa deactivates enzymes that regulate thiol-disulfide homeostasis and promotes neuronal cell death: implications for therapy of Parkinson's disease.
Parkinson's disease (PD), characterized by dopaminergic neuronal loss, is attributed to oxidative stress, diminished glutathione (GSH) levels, mitochondrial dysfunction, and protein aggregation. Treatment of PD involves chronic administration of Levodopa (l-DOPA) which is a pro-oxidant and may disrupt sulfhydryl homeostasis. The goal of these studies is to elucidate the effects of l-DOPA on thiol homeostasis in a model akin to PD, i.e., immortalized dopaminergic neurons (SHSY5Y cells) with diminished GSH content. These neurons exhibit hypersensitivity to l-DOPA-induced cell death, which is attributable to concomitant inhibition of the intracellular thiol disulfide oxidoreductase enzymes. Glutaredoxin (Grx) was deactivated in a dose-dependent fashion, but its content was unaffected. Glutathione disulfide (GSSG) reductase (GR) activity was not altered. Selective knockdown of Grx resulted in an increased level of apoptosis, documenting the role of the Grx system in neuronal survival. l-DOPA treatments also led to decreased activities of thioredoxin (Trx) and thioredoxin reductase (TR), concomitant with diminution of their cellular contents. Selective chemical inhibition of TR activity led to an increased level of apoptosis, documenting the Trx system's contribution to neuronal viability. To investigate the mechanism of inhibition at the molecular level, we treated the each isolated enzyme with oxidized l-DOPA. GR, Trx, and TR activities were little affected. However, Grx was inactivated in a time- and concentration-dependent fashion indicative of irreversible adduction of dopaquinone to its nucleophilic active-site Cys-22, consistent with the intracellular loss of Grx activity but not Grx protein content after l-DOPA treatment. Overall l-DOPA is shown to impair the collaborative contributions of the Grx and Trx systems to neuron survival.


Preparation of packed red blood cell units in the blood bank: Alteration in red blood cell deformability.
Donated blood is stored in the blood bank as packed red blood cell units. In the process of packed cells preparation, the red blood cells (RBCs) are subjectedto high level of shear stress, which can induce alterations in their properties. In the present study, we examined the effect of packed RBCs preparation (which included leuko-filtration) on red cell deformability. Blood samples were collected from 25 healthy donors and from corresponding units of packed RBCs. The portion of undeformable cells (%UDFC) was determined for each sample. The median value of %UDFC was equal to 6.75 ± 0.70 %, for freshly-donated RBCs, and to 6.36 ± 0.51 %, for packed cells. Wherein, %UDFC may increase or decrease following packed cells preparation, depending upon the initial portion of undeformable cells. Likely, exposure of RBCs to high shear stress, during packed cells preparation, induces opposing effects: (a) removal/destruction of rigid (undeformable) cells, thereby reducing their total amount (i.e., decreasing the %UDFC) on the one hand, and (b) mechanical damage to the cell membrane and subsequent reduction of the cell deformability (thereby increasing the %UDFC) on the other. As a consequence, the final impact of packed cells preparation is primarily determined by the initial state of erythrocytes in the blood of the donor.


Is there any relationship between physical activity level and patterns, and physical performance in children?
It is often assumed that physical activity (PA) and physical performance during childhood and adolescence are beneficial for health during adulthood, but a positive relationship between PA and physical performance has not been precisely clarified in children. The lack or the weakness of the relationships between PA and physical performance could be due to the measure of PA. If the use of accelerometry is considered as an objective and common measure of PA, the real patterns of children's habitual PA must be reflected. The aim of this study was to investigate the relationship between the levels and patterns of PA assessed with high frequency accelerometry and physical performance in young children. Eighty-six boys and 101 girls aged 6-12 years participated in this study. Physical activity was measured over a 7-day period, using a 5-s epoch. Physical performance was assessed by means of EUROFIT tests (anthropometrics, standing broad jump, the 10 × 5 meter shuttle run, the sit-and-reach, the handgrip, the number of sit-ups in 30 seconds, the 20-meter shuttle run). No relationship was found between PA and physical performance. In boys only, body fatness was negatively associated with vigorous PA (r = -0.38, p < 0.001) and very high PA (r = -0.35, p < 0.01), in contrast to light PA (r = 0.28, p < 0.01), which was positively related to body fatness. In 6- to- 12 year- old children, the more active children were not the fittest. Our results also underline the need for uniformity in approach to measurement of PA, body composition and health-related fitness between studies.


Local variations in microfungal populations on Pinus sylvestris needles.
We studied the fungal colonization of Pinus sylvestris needles in two neighbouring sites, comparing stands of isolated and grouped trees. We observed large variations among the proportions of needles bearing fruit bodies of Cyclaneusma minus, Lophodermium pinastri, Verticicladium trifidum and black lines characteristic of L. pinastri colonization. Variations between sites and within trees were greater than that between stands or between trees. The frequency of L. pinastri colonization was negatively correlated with C. minus fruit body frequency, while the frequency of V. trifidum conidiophores was positively correlated with L. pinastri colonization frequency without fruiting, and negatively correlated with C. minus apothecia frequency. Although L. pinastri black lines and C. minus apothecia were nearly randomly associated on individual needles in each sample, the two fungi occupied different segments when they occupied the same needle. These patterns at needle and sample scales do not explain the negative correlation between the frequencies of these two species observed at larger scales. In each sample, frequency of V. trifidum conidiophores was highest on needles colonized by L. pinastri without fruiting. On individual needles, V. trifidum conidiophores developed on segments colonized by L. pinastri without fruiting, but not on segments bearing fruit bodies of L. pinastri or C. minus. These patterns at needle and sample scales were consistent with the correlations between frequencies observed at larger scales. These results were compared to variations observed with stand age and climate in others studies. The observed variations might result from both microclimate variations and fungal interactions.


Cholera toxin B subunit-five-stranded α-helical coiled-coil fusion protein: "five-to-five" molecular chimera displays robust physicochemical stability.
To create a physicochemically stable cholera toxin (CT) B subunit (CTB), it was fused to the five-stranded α-helical coiled-coil domain of cartilage oligomeric matrix protein (COMP). The chimeric fusion protein (CTB-COMP) was expressed in Pichia pastoris, predominantly as a pentamer, and retained its affinity for the monosialoganglioside GM1, a natural receptor of CT. The fusion protein displayed thermostability, tolerating the boiling temperature of water for 10min, whereas unfused CTB readily dissociated to its monomers and lost its affinity for GM1. The fusion protein also displayed resistance to strong acid at pHs as low as 0.1, and to the protein denaturant sodium dodecyl sulfate at concentrations up to 10%. Intranasal administration of the fusion protein to mice induced anti-B subunit serum IgG, even after the protein was boiled, whereas unfused CTB showed no thermostable mucosal immunogenicity. This study demonstrates that CTB fused to a pentameric α-helical coiled coil has a novel physicochemical phenotype, which may provide important insight into the molecular design of enterotoxin-B-subunit-based vaccines and vaccine delivery molecules.


Epidemiology of Ankylosing spondylitis in Rochester, Minnesota, 1935-1973.
The Mayo Clinic records linkage facility for residents of Rochester, Minnesota, Yielded 102 cases of ankylosing spondylitis (AS) diagnosed from 1935 through 1973. The incidence did not change significantly over the 39 years. Three times as many males as females were affected. In contrast to another recent report, survivorship of males with AS was not different from that of the general population, whereas survivorship of females with AS was reduced. The overall prevalence was 129/100,000.


Applications of Single-Molecule Vibrational Spectroscopic Techniques for the Structural Investigation of Amyloid Oligomers.
Amyloid oligomeric species, formed during misfolding processes, are believed to play a major role in neurodegenerative and metabolic diseases. Deepening the knowledge about the structure of amyloid intermediates and their aggregation pathways is essential in understanding the underlying mechanisms of misfolding and cytotoxicity. However, structural investigations are challenging due to the low abundance and heterogeneity of those metastable intermediate species. Single-molecule techniques have the potential to overcome these difficulties. This review aims to report some of the recent advances and applications of vibrational spectroscopic techniques for the structural analysis of amyloid oligomers, with special focus on single-molecule studies.


Radiosensitivity of early and late M-phase HeLa cells isolated by a combination of fluorescent ubiquitination-based cell cycle indicator (Fucci) and mitotic shake-off.
The mitotic shake-off method revealed the remarkable variation of radiosensitivity of HeLa cells during the cell cycle: M phase shows the greatest radiosensitivity and late S phase the greatest radioresistance. This method harvests all M-phase cells with a round shape, making it impossible to further subdivide M-phase cells. Recently, the fluorescent ubiquitination-based cell cycle indicator (Fucci) was developed; this system basically causes cells in G(1) to emit red fluorescence and other cells to emit green fluorescence. Because the green fluorescence rapidly disappears at late M phase, two-dimensional flow cytometry analysis can usually detect a green(high)/red(low) fraction including S-, G(2)- and early M-phase cells but not a transitional fraction between green(high)/red(low) and green(low)/red(low) including late M-phase cells. However, combining the shake-off method concentrated the transitional fraction, which enabled us to separate early and late M-phase cells without using any drugs. Here we demonstrate for the first time that cells in early M phase are more radiosensitive than those in late M phase, implying that early M phase is the most radiosensitive sub-phase during the cell cycle.


Walking stabilizes cognitive functioning in Alzheimer's disease (AD) across one year.
AD is a public health epidemic, which seriously impacts cognition, mood and daily activities; however, one type of activity, exercise, has been shown to alter these states. Accordingly, we sought to investigate the relationship between exercise and mood, in early-stage AD patients (N=104) from California, over a 1-year period. Patients completed the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and Blessed-Roth Dementia Rating Scale (BRDRS), while their caregivers completed the Yale Physical Activity Survey (YALE), Profile of Mood States (POMS), the Neuropsychiatric Inventory (NPI) and Functional Abilities Questionnaire (FAQ). Approximately half of the participants were female, from a variety of ethnic groups (Caucasian=69.8%; Latino/Hispanic Americans=20.1%). Our results demonstrated that the patients spent little time engaged in physical activity in general, their overall activity levels decreased over time, and this was paired with a change in global cognition (e.g., MMSE total score) and affect/mood (e.g., POMS score). Patients were parsed into Active and Sedentary groups based on their Yale profiles, with Active participants engaged in walking activities, weekly, over 1 year. Here, Sedentary patients had a significant decline in MMSE scores, while the Active patients had an attenuation in global cognitive decline. Importantly, among the Active AD patients, those individuals who engaged in walking for more than 2 h/week had a significant improvement in MMSE scores. Structured clinical trials which seek to increase the amount of time AD patients were engaged in walking activities and evaluate the nature and scope of beneficial effects in the brain are warranted.


Structural analysis of the umu operon required for inducible mutagenesis in Escherichia coli.
The nucleotide sequence of a 2.8-kilobase fragment of the Escherichia coli chromosome containing the umuDC genes has been determined. The DNA sequence specifies two open reading frames of 417 and 1266 nucleotides encoding proteins with calculated molecular weights of 15,063 and 47,677, respectively. From these and the previous results of genetic and biochemical studies on the cloned genes, we conclude that the former is the umuD and the latter is the umuC gene. In vitro transcription of the regulatory region of the umu operon revealed that (i) upstream of the coding region there is a promoter-operator complex having the consensus sequence, CTGTATATAAAAACAG, of an SOS box, (ii) transcription of the umu operon begins at an adenine residue in the SOS box, and (iii) the LexA protein binds to the operator region, with an equilibrium dissociation constant (Kd) of 0.2, thereby repressing the transcription of the umuDC genes. These results indicate that the expression of the umu operon is under the coordinated control of the recA lexA gene products.


Availability optimization of power generating units used in sewage treatment plants using metaheuristic techniques.
Metaheuristic techniques have been utilized extensively to predict industrial systems' optimum availability. This prediction phenomenon is known as the NP-hard problem. Though, most of the existing methods fail to attain the optimal solution due to several limitations like slow rate of convergence, weak computational speed, stuck in local optima, etc. Consequently, in the present study, an effort has been made to develop a novel mathematical model for power generating units assembled in sewage treatment plants. Markov birth-death process is adopted for model development and generation of Chapman-Kolmogorov differential-difference equations. The global solution is discovered using metaheuristic techniques, namely genetic algorithm and particle swarm optimization. All time-dependent random variables associated with failure rates are considered exponentially distributed, while repair rates follow the arbitrary distribution. The repair and switch devices are perfect and random variables are independent. The numerical results of system availability have been derived for different values of crossover, mutation, several generations, damping ratio, and population size to attain optimum value. The results were also shared with plant personnel. Statistical investigation of availability results justifies that particle swarm optimization outdoes genetic algorithm in predicting the availability of power-generating systems. In present study a Markov model is proposed and optimized for performance evaluation of sewage treatment plant. The developed model is one that can be useful for sewage treatment plant designers in establishing new plants and purposing maintenance policies. The same procedure of performance optimization can be adopted in other process industries too.


The historical demography and genetic variation of the endangered Cycas multipinnata (Cycadaceae) in the red river region, examined by chloroplast DNA sequences and microsatellite markers.
Cycas multipinnata C.J. Chen & S.Y. Yang is a cycad endemic to the Red River drainage region that occurs under evergreen forest on steep limestone slopes in Southwest China and northern Vietnam. It is listed as endangered due to habitat loss and over-collecting for the ornamental plant trade, and only several populations remain. In this study, we assess the genetic variation, population structure, and phylogeography of C. multipinnata populations to help develop strategies for the conservation of the species. 60 individuals from six populations were used for chloroplast DNA (cpDNA) sequencing and 100 individuals from five populations were genotyped using 17 nuclear microsatellites. High genetic differentiation among populations was detected, suggesting that pollen or seed dispersal was restricted within populations. Two main genetic clusters were observed in both the cpDNA and microsatellite loci, corresponding to Yunnan China and northern Vietnam. These clusters indicated low levels of gene flow between the regions since their divergence in the late Pleistocene, which was inferred from both Bayesian and coalescent analysis. In addition, the result of a Bayesian skyline plot based on cpDNA portrayed a long history of constant population size followed by a decline in the last 50,000 years of C. multipinnata that was perhaps affected by the Quaternary glaciations, a finding that was also supported by the Garza-Williamson index calculated from the microsatellite data. The genetic consequences produced by climatic oscillations and anthropogenic disturbances are considered key pressures on C. multipinnata. To establish a conservation management plan, each population of C. multipinnata should be recognized as a Management Unit (MU). In situ and ex situ actions, such as controlling overexploitation and creating a germplasm bank with high genetic diversity, should be urgently implemented to preserve this species.


The IQGAP Iqg1 is a regulatory target of CDK for cytokinesis in Candida albicans.
Cyclin-dependent kinases (CDKs) drive and coordinate multiple cell-cycle events, including construction and contraction of the actomyosin ring during cytokinesis. However, it remains unclear whether CDKs regulate cytokinesis by directly targeting components of the ring. In a search for proteins containing consensus CDK phosphorylation sites in Candida albicans, we found that the IQGAP Iqg1 contains two dense clusters of 19 such sites flanking the actin-interacting CH domain. Here, we show that Iqg1 is indeed a phosphoprotein that undergoes cell-cycle-dependent phosphorylation and can be phosphorylated by purified Clb-Cdc28 kinases in vitro. Mass spectrometry identified several phosphoserine and phosphothreonine residues among these CDK sites. Mutating 15 of the CDK phosphorylation sites with alanine markedly reduced Iqg1 phosphorylation in vivo. The 15A mutation greatly stabilized Iqg1, caused both premature assembly and delayed disassembly of the actomyosin ring, blocked Iqg1 interaction with the actin-nucleating proteins Bni1 and Bnr1, and resulted in defects in cytokinesis. Our data therefore strongly support the idea that the Cdc28 CDK regulates cytokinesis partly by directly phosphorylating the actomyosin ring component Iqg1.


A sensitive assay for anti-phosphatidylethanol-amine antibody in patients with recurrent fetal loss.
There is strong evidence that anti-phospholipid antibodies is implicated in thrombosis and recurrent fetal death. In recent years, it has been suggested that anti-phosphatidylethanolamine (PE) antibody is an important antibody of this type. In the present study, we established a sensitive enzyme linked immunosorbent assay (ELISA) to detect anti-PE antibodies and examined the relationship between the anti-PE antibody level in serum and recurrent abortion. The improvement of the assay was made by treating PE with 1.0% acetic acid in methanol solution prior to its application to the microplates. This treatment markedly increased the antigenicity of PE. Using this modified ELISA, anti-PE antibodies in 10 patients with a history of recurrent fetal loss were measured before and after therapy during the last period of their pregnancies. IgG anti-PE antibodies were detected in all 10 patients. Four patients exhibiting high titers of IgG anti-PE antibody experienced subsequent intrauterine fetal death (IUFD), while the other 6 patients, whose titers of IgG anti-PE antibody had decreased with therapy, had live births. These results suggest that this modified ELISA for estimating IgG anti-PE antibody is a valuable tool for the diagnosis and prognosis of patients with recurrent fetal loss.


Liquid secretion properties of airway submucosal glands.
The tracheobronchial submucosal glands secrete liquid that is important for hydrating airway surfaces, supporting mucociliary transport, and serving as a fluid matrix for numerous secreted macromolecules including the gel-forming mucins. This review details the essential structural elements of airway glands and summarizes what is currently known regarding the ion transport processes responsible for producing the liquid component of gland secretion. Liquid secretion most likely arises from serous cells and is principally under neural control with muscarinic agonists, substance P, and vasoactive intestinal peptide (VIP) functioning as effective secretogogues. Liquid secretion is driven by the active transepithelial secretion of both Cl(-) and HCO(3)(-) and at least a portion of this process is mediated by the cystic fibrosis transmembrane conductance regulator (CFTR), which is highly expressed in glands. The potential role of submucosal glands in cystic fibrosis lung disease is discussed.


What Happens After Treatment? Long-Term Effects of Continued Substance Use, Psychiatric Problems and Help-Seeking on Social Status of Alcohol-Dependent Individuals.
We examined whether alcohol-dependent individuals with sustained substance use or psychiatric problems after completing treatment were more likely to experience low social status and whether continued help-seeking would improve outcomes. Ongoing alcohol, drug and psychiatric problems after completing treatment were associated with increased odds of low social status (unemployment, unstable housing and/or living in high-poverty neighborhood) over 7 years. The impact of drug problems declined over time, and there were small, delayed benefits of AA attendance on social status. Alcohol-dependent individuals sampled from public and private treatment programs (N = 491; 62% male) in Northern California were interviewed at treatment entry and 1, 3, 5 and 7 years later. Random effects models tested relationships between problem severity (alcohol, drug and psychiatric problems) and help-seeking (attending specialty alcohol/drug treatment and Alcoholics Anonymous, AA) with low social status (unemployment, unstable housing and/or living in a high-poverty neighborhood) over time. The proportion of participants experiencing none of the indicators of low social status increased between baseline and the 1-year follow-up and remained stable thereafter. Higher alcohol problem scores and having any drug and/or psychiatric problems in the years after treatment were associated with increased odds of low social status over time. An interaction of drug problems with time indicated the impact of drug problems on social status declined over the 7-year period. Both treatment-seeking and AA attendance were associated with increased odds of low social status, although lagged models suggested there were small, delayed benefits of AA attendance on improved social status over time. Specialty addiction treatment alone was not sufficient to have positive long-term impacts on social status and social integration of most alcohol-dependent people.


Accuracy of scanography using storage phosphor plate systems and film for assessment of mandibular third molars.
The aim of this study was to compare the diagnostic accuracy of two digital photostimulable storage phosphor (PSP) systems and film for assessment of mandibular third molars before surgery. 110 patients were referred to have both their mandibular third molars removed. Each patient underwent a radiographic examination with scanography using either Digora (Soredex, Helsinki, Finland) and film or VistaScan (Dürr Dental, Beitigheim-Bissingen, Germany) and film in a randomized paired design. Two observers examined the following variables on the scanograms: bone coverage, angulation of the tooth in the bone, number of roots, root morphology and the relationship to the mandibular canal. In 75 of the pairs (Digora/film pair = 38 and Vista/film pair = 37) both third molars were eventually removed. During and after surgery the same variables were assessed, which served as reference standard for the radiographic assessments. The Wilcoxon signed-rank test tested differences in accuracy (radiographic compared with surgical findings) between Digora/film and between Vista/film. There was no statistically significant difference between the diagnostic accuracy of film and either of the two digital receptors for assessment of mandibular third molars before surgery (P > 0.05), although Digora obtained a higher accuracy than film. Scanography is a valuable method for examination of mandibular third molars before removal and the PSP digital receptors in this study were equal to film for this purpose.


Comprehension skill and global coherence: a paradoxical picture of poor comprehenders' abilities.
The authors investigated good and poor comprehenders' maintenance of global coherence during reading. Participants read stories in which a character's action was consistent or inconsistent with a description of the character presented earlier in the story. In Experiment 1, the description and action were adjacent in the text (local coherence) or were separated by intervening text (global coherence). Both groups of comprehenders read inconsistent actions more slowly than consistent actions in the local coherence condition, but only good comprehenders showed the reading time difference in the global coherence condition. In Experiment 2, the authors disconfirmed the hypothesis that poor comprehenders fail to maintain global coherence because they fail to activate prior text information. Thus, the results present a paradoxical picture in which poor readers activate relevant knowledge during reading but fail to integrate it into their developing representation.