Molecular microbial diversity in soils from eastern Amazonia: evidence for unusual microorganisms and microbial population shifts associated with deforestation.
Although the Amazon Basin is well known for its diversity of flora and fauna, this report represents the first description of the microbial diversity in Amazonian soils involving a culture-independent approach. Among the 100 sequences of genes coding for small-subunit rRNA obtained by PCR amplification with universal small-subunit rRNA primers, 98 were bacterial and 2 were archaeal. No duplicate sequences were found, and none of the sequences had been previously described. Eighteen percent of the bacterial sequences could not be classified in any known bacterial kingdom. Two sequences may represent a unique branch between the vast majority of bacteria and the deeply branching, predominantly thermophilic bacteria. Five sequences formed a clade that may represent a novel group within the class Proteobacteria. In addition, rRNA intergenic spacer analysis was used to show significant microbial population differences between a mature forest soil and an adjacent pasture soil.


What do patients with cancer and their families value most at the end of life? A critical analysis of advance care planning.
Advance care planning (ACP) is defined in a variety of ways, although it is widely understood as a process undertaken by patients, when they have capacity, to define and communicate their treatment preferences for future care. Few studies have explored the meaning and importance patients place on their ability to participate in directing their medical care. This study aimed to explore how cancer patients and their family members value autonomy at the end of life (EoL) and understand how this may impact on the way they develop and act on EoL decisions and planning. Data were collected through in-depth semi-structured interviews with patients and family members of people with cancer. Participants were recruited from metropolitan cancer centres in Sydney, Australia. Interviews were analysed using thematic analysis. Findings from 11 participant interviews (five patients with cancer and six family members) were organised into four themes: 'the threat of death and cancer'; 'patients seek trust and safety at the end of life'; 'doctors are human and the healthcare system has limitations'; and 'the role of ACP'. Participants experienced cancer and death as a 'threat', to self and others and as something 'uncontrollable'. ACP was seen to have the potential to enhance EoL care by contributing to decreasing uncertainty, enhancing comfort, helping to achieve 'the small things', and in helping the family 'know what to do'. However, participants were, in general, distrustful of documentation and cognisant of uncertainty around medical outcomes and the legal limitations of their capacity to influence care. These findings suggest that models of ACP which are constructed around patients' 'rights' to determine what happens to their bodies may do little to enhance the quality of EoL care, as patients value veracity, trust and comfort at the EoL more than autonomy. Quality EoL care should focus on paying increased attention to the relational and social aspects of care.


Medical Provider Ballistic Protection at Active Shooter Events.
There is some controversy about whether ballistic protective equipment (body armor) is required for medical responders who may be called to respond to active shooter mass casualty incidents. In this article, we describe the ongoing evolution of recommendations to optimize medical care to injured victims at such an incident. We propose that body armor is not mandatory for medical responders participating in a rapid-response capacity, in keeping with the Hartford Consensus and Arlington Rescue Task Force models. However, we acknowledge that the development and implementation of these programs may benefit from the availability of such equipment as one component of risk mitigation. Many police agencies regularly retire body armor on a defined time schedule before the end of its effective service life. Coordination with law enforcement may allow such retired body armor to be available to other public safety agencies, such as fire and emergency medical services, providing some degree of ballistic protection to medical responders at little or no cost during the rare mass casualty incident. To provide visual demonstration of this concept, we tested three "retired" ballistic vests with ages ranging from 6 to 27 years. The vests were shot at close range using police-issue 9mm, .40 caliber, .45 caliber, and 12-gauge shotgun rounds. Photographs demonstrate that the vests maintained their ballistic protection and defeated all of these rounds.


The interplay of stressful life events and coping skills on risk for suicidal behavior among youth students in contemporary China: a large scale cross-sectional study.
Stressful life events are common among youth students and may induce psychological problems and even suicidal behaviors in those with poor coping skills. This study aims to assess the influence of stressful life events and coping skills on risk for suicidal behavior and to elucidate the underlying mechanism using a large sample of university students in China. 5972 students, randomly selected from 6 universities, completed the questionnaire survey. Logistic regression analysis was performed to estimate the effect of stressful life events and coping skills on risk for suicidal behavior. Bayesian network was further adopted to probe their probabilistic relationships. Of the 5972 students, 7.64% reported the presence of suicidal behavior (attempt or ideation) within the past one year period. Stressful life events such as strong conflicts with classmates and a failure in study exam constituted strong risk factors for suicidal behavior. The influence of coping skills varied according to the strategies adapted toward problems with a high score of approach coping skills significantly associated with a reduced risk of suicidal behavior. The Bayesian network indicated that the probability of suicidal behavior associated with specific life events was to a large extent conditional on coping skills. For instance, a stressful experience of having strong conflicts with classmates could result in a probability of suicidal behavior of 21.25% and 15.36% respectively, for female and male students with the score of approach coping skills under the average. Stressful life events and deficient coping skills are strong risk factors for suicidal behavior among youth students. The results underscore the importance of prevention efforts to improve coping skills towards stressful life events.


Predicting and understanding law-making with word vectors and an ensemble model.
Out of nearly 70,000 bills introduced in the U.S. Congress from 2001 to 2015, only 2,513 were enacted. We developed a machine learning approach to forecasting the probability that any bill will become law. Starting in 2001 with the 107th Congress, we trained models on data from previous Congresses, predicted all bills in the current Congress, and repeated until the 113th Congress served as the test. For prediction we scored each sentence of a bill with a language model that embeds legislative vocabulary into a high-dimensional, semantic-laden vector space. This language representation enables our investigation into which words increase the probability of enactment for any topic. To test the relative importance of text and context, we compared the text model to a context-only model that uses variables such as whether the bill's sponsor is in the majority party. To test the effect of changes to bills after their introduction on our ability to predict their final outcome, we compared using the bill text and meta-data available at the time of introduction with using the most recent data. At the time of introduction context-only predictions outperform text-only, and with the newest data text-only outperforms context-only. Combining text and context always performs best. We conducted a global sensitivity analysis on the combined model to determine important variables predicting enactment.


The distribution and targeting of neuronal voltage-gated ion channels.
Voltage-gated ion channels have to be at the right place in the right number to endow individual neurons with their specific character. Their biophysical properties together with their spatial distribution define the signalling characteristics of a neuron. Improper channel localization could cause communication defects in a neuronal network. This review covers recent studies of mechanisms for targeting voltage-gated ion channels to axons and dendrites, including trafficking, retention and endocytosis pathways for the preferential localization of particular ion channels. We also discuss how the spatial localization of these channels might contribute to the electrical excitability of neurons, and consider the need for future work in this emerging field.


Hydrogen retention in beryllium: concentration effect and nanocrystalline growth.
We herein report on the formation of BeD2 nanocrystalline domes on the surface of a beryllium sample exposed to energetic deuterium ions. A polycrystalline beryllium sample was exposed to D ions at 2 keV/atom leading to laterally averaged deuterium areal densities up to 3.5 10(17) D cm(-2), and studied using nuclear reaction analysis, Raman microscopy, atomic force microscopy, optical microscopy and quantum calculations. Incorporating D in beryllium generates a tensile stress that reaches a plateau at ≈1.5 10(17) D cm(-2). For values higher than 2.0 10(17) cm(-2), we observed the growth of ≈90 nm high dendrites, covering up to 10% of the surface in some zones of the sample when the deuterium concentration was 3 × 10(17) D cm(-2). These dendrites are composed of crystalline BeD2, as evidenced by Raman microscopy and quantum calculations. They are candidates to explain low temperature thermal desorption spectroscopy peaks observed when bombarding Be samples with D ions with fluencies higher than 1.2 10(17) D cm(-2).


Interaction of relaxin-like gonad-stimulating substance with ovarian follicle cells of the starfish Asterina pectinifera.
Previously, gonad-stimulating substance (GSS), which acts as a gonadotropin, was purified from radial nerves of the starfish Asterina pectinifera and its structure was elucidated. Here, the interaction of GSS with receptors was examined in ovarian follicle cells, a target of GSS. In competitive experiments using radioiodinated and radioinert GSS, highly specific binding was observed in the microsomal/plasma membrane fraction of follicle cells. GSS scarcely bound in the cytosolic fraction. Scatchard plots showed the numbers of binding sites (NBS) in whole homogenate and the crude membrane to be 1.65 and 3.42 pmoles/mg protein, respectively. Dissociation constant (K (d)) values in these two preparations were almost the same at about 0.6-0.7 nM. Furthermore, it was shown that GSS stimulated adenylyl cyclase activity in follicle cell membranes in a dose-dependent manner that required GTP. Immunoblotting with specific antibodies for G-protein subunits after SDS-PAGE of the membrane preparation showed both stimulatory (Gs) and inhibitory (Gi) regulatory α-subunits for adenylyl cyclase and a β-subunit. The results strongly suggest that GSS interacts with G-protein-coupled receptors (GPCR) located in the follicle cell membrane to stimulate Gs-protein and adenylyl cyclase activity.


Morphological and molecular characterization of several actinophages isolated from soil which lyse Streptomyces cattleya or S. venezuelae.
Several lytic and lysogenic actinophages were isolated from soil samples infected with Streptomyces cattleya and S. venezuelae. The morphologies and some biological properties of the phages, and the physico-chemical characteristics of their DNAs, were compared. Electron micrographs indicated that all the phage heads were of an icosahedral form, but head size and length of the tail varied. Two of the phages had a broad host range; the other isolates could lyse only a limited number of species. The molecular sizes of the phage DNAs were between 32.2 and 98.5 kb as estimated by electron microscopy and restriction enzyme analysis. The same study also indicated that one of the DNA species contained cohesive ends. The G + C content of the DNAs ranged between 45.1 and 74.2 mol % as estimated from melting studies. Sedimentation velocity experiments implied that several of the phage DNAs were probably heavily glycosylated or methylated. These modifications might explain the partial or slow digestion of some of the DNAs by several of the 23 restriction enzymes tested. Protoplasts of the appropriate Streptomyces strains could be efficiently transfected with phage DNA in the presence of 25% (w/v) polyethylene glycol (mol. wt 6000).


A coactivator role of CARM1 in the dysregulation of β-catenin activity in colorectal cancer cell growth and gene expression.
Aberrant activation of Wnt/β-catenin signaling, resulting in the expression of Wnt-regulated oncogenes, is recognized as a critical factor in the etiology of colorectal cancer. Occupancy of β-catenin at promoters of Wnt target genes drives transcription, but the mechanism of β-catenin action remains poorly understood. Here, we show that CARM1 (coactivator-associated arginine methyltransferase 1) interacts with β-catenin and positively modulates β-catenin-mediated gene expression. In colorectal cancer cells with constitutively high Wnt/β-catenin activity, depletion of CARM1 inhibits expression of endogenous Wnt/β-catenin target genes and suppresses clonal survival and anchorage-independent growth. We also identified a colorectal cancer cell line (RKO) with a low basal level of β-catenin, which is dramatically elevated by treatment with Wnt3a. Wnt3a also increased the expression of a subset of endogenous Wnt target genes, and CARM1 was required for the Wnt-induced expression of these target genes and the accompanying dimethylation of arginine 17 of histone H3. Depletion of β-catenin from RKO cells diminished the Wnt-induced occupancy of CARM1 on a Wnt target gene, indicating that CARM1 is recruited to Wnt target genes through its interaction with β-catenin and contributes to transcriptional activation by mediating events (including histone H3 methylation) that are downstream from the actions of β-catenin. Therefore, CARM1 is an important positive modulator of Wnt/β-catenin transcription and neoplastic transformation, and may thereby represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/β-catenin signaling.


Reproductive endocrine disruption in a sentinel species (Chrysemys picta) on Cape Cod, Massachusetts.
Freshwater turtles (Chrysemys picta) were collected from two sites on Cape Cod, MA. One site (Moody Pond), adjacent to the Massachusetts Military Reservation (MMR), was considered potentially impacted by toxic agents deriving from contaminant point sources on the MMR. The second (reference) site (Washburn Pond), to the east of the MMR, was considered not impacted by these pollutants and was chosen as a control site. Plasma estradiol 17 beta and vitellogenin were significantly lower in female turtles from Moody Pond. Ovarian follicular analysis indicated a significant decrease in the >16.00-mm follicular cohort in Moody Pond female turtles compared with Washburn Pond animals. Although testicular weight was lower at the Moody Pond site, histology, plasma testosterone, and sperm number were similar to these parameters in Washburn Pond animals. The data suggest that in Moody Pond, the reproductive capacity of turtles may be negatively affected by contaminants from the MMR.


The Effect of Surgeon Caseload on the Relative Revision Rate of Cemented and Cementless Unicompartmental Knee Replacements: An Analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.
Unicompartmental knee replacement (UKR) offers substantial benefits compared with total knee replacement (TKR) but is associated with higher revision rates. Data from registries suggest that revision rates for cementless UKR implants are lower than those for cemented implants. It is not known how much of this difference is due to the implant or to other factors, such as a greater proportion of high-volume surgeons using cementless implants. We aimed to determine the effect of surgeon caseload on the revision rate of matched cemented and cementless UKRs. From a group of 40,522 Oxford (Zimmer Biomet) UKR implants (30,814 cemented, 9,708 cementless) recorded in the National Joint Registry, 14,814 (7,407 cemented, 7,407 cementless) were propensity-score matched. Surgeons were categorized into 3 groups: low volume (<10 cases/year), medium volume (10 to <30 cases/year), and high volume (≥30 cases/year). The effect of caseload on the relative risk of revision was assessed with use of Cox regression. The 10-year survival rates for unmatched cementless and cemented UKR implants were 93.3% (95% confidence interval [CI] = 89.8% to 95.7%) and 89.1% (95% CI = 88.6% to 89.6%), respectively, with the difference being significant (hazard ratio [HR] = 0.59; p < 0.001). Cementless UKR implants had a greater proportion of high-volume surgeon users than cemented implants (30.4% compared with 15.1%). Following matching, the 10-year survival rates were 93.2% (95% CI = 89.7% to 95.6%) and 90.2% (95% CI = 87.5% to 92.3%), which were still significantly different (HR = 0.76; p = 0.002). The 10-year survival rates for matched cementless and cemented UKR implants were 86.8% (95% CI = 73.6% to 93.7%) and 81.8% (95% CI = 73.0% to 88.0%) for low-volume surgeons, 94.3% (95% CI = 92.2% to 95.9%) and 92.5% (95% CI = 89.9% to 94.5%) for medium-volume surgeons, and 97.5% (95% CI = 96.5% to 98.2%) and 94.2% (95% CI = 90.8% to 96.4%) for high-volume surgeons. The revision rate for cementless implants was lower for surgeons in all 3 caseload groups (HR = 0.74, 0.79, 0.80, respectively). Cementless fixation decreased the revision rate by about a quarter, whatever the surgeon caseload. Caseload had a profound effect on implant survival. Low-volume surgeons had a high revision rate with cemented or cementless fixation and therefore should consider either stopping or doing more UKR procedures. High-volume surgeons performing cementless UKR demonstrated a 10-year survival rate of 97.5%, which was similar to that reported in registries for the best-performing TKRs. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Negative polarity illusions and the format of hierarchical encodings in memory.
Linguistic illusions have provided valuable insights into how we mentally navigate complex representations in memory during language comprehension. Two notable cases involve illusory licensing of agreement and negative polarity items (NPIs), where comprehenders fleetingly accept sentences with unlicensed agreement or an unlicensed NPI, but judge those same sentences as unacceptable after more reflection. Existing accounts have argued that illusions are a consequence of faulty memory access processes, and make the additional assumption that the encoding of the sentence remains fixed over time. This paper challenges the predictions made by these accounts, which assume that illusions should generalize to a broader set of structural environments and a wider range of syntactic and semantic phenomena. We show across seven reading-time and acceptability judgment experiments that NPI illusions can be reliably switched "on" and "off", depending on the amount of time from when the potential licensor is processed until the NPI is encountered. But we also find that the same profile does not extend to agreement illusions. This contrast suggests that the mechanisms responsible for switching the NPI illusion on and off are not shared across all illusions. We argue that the contrast reflects changes over time in the encoding of the semantic/pragmatic representations that can license NPIs. Just as optical illusions have been informative about the visual system, selective linguistic illusions are informative not only about the nature of the access mechanisms, but also about the nature of the encoding mechanisms.


The influence of a priori grouping on inference of genetic clusters: simulation study and literature review of the DAPC method.
Inference of genetic clusters is a key aim of population genetics, sparking development of numerous analytical methods. Within these, there is a conceptual divide between finding de novo structure versus assessment of a priori groups. Recently developed, Discriminant Analysis of Principal Components (DAPC), combines discriminant analysis (DA) with principal component (PC) analysis. When applying DAPC, the groups used in the DA (specified a priori or described de novo) need to be carefully assessed. While DAPC has rapidly become a core technique, the sensitivity of the method to misspecification of groups and how it is being empirically applied, are unknown. To address this, we conducted a simulation study examining the influence of a priori versus de novo group designations, and a literature review of how DAPC is being applied. We found that with a priori groupings, distance between genetic clusters reflected underlying FST. However, when migration rates were high and groups were described de novo there was considerable inaccuracy, both in terms of the number of genetic clusters suggested and placement of individuals into those clusters. Nearly all (90.1%) of 224 studies surveyed used DAPC to find de novo clusters, and for the majority (62.5%) the stated goal matched the results. However, most studies (52.3%) omit key run parameters, preventing repeatability and transparency. Therefore, we present recommendations for standard reporting of parameters used in DAPC analyses. The influence of groupings in genetic clustering is not unique to DAPC, and researchers need to consider their goal and which methods will be most appropriate.


Diabetes in Asia: epidemiology, risk factors, and pathophysiology.
With increasing globalization and East-West exchanges, the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implications. To review recent data in epidemiologic trends, risk factors, and complications of type 2 diabetes in Asia. Search of MEDLINE using the term diabetes and other relevant keywords to identify meta-analyses, systematic reviews, large surveys, and cohort studies. Separate searches were performed for specific Asian countries. The review was limited to English-language articles published between January 1980 and March 2009; publications on type 1 diabetes were excluded. The prevalence of diabetes in Asian populations has increased rapidly in recent decades. In 2007, more than 110 million individuals in Asia were living with diabetes, with a disproportionate burden among the young and middle aged. Similarly, rates of overweight and obesity are increasing sharply, driven by economic development, nutrition transition, and increasingly sedentary lifestyles. The "metabolically obese" phenotype (ie, normal body weight with increased abdominal adiposity) is common in Asian populations. The increased risk of gestational diabetes, combined with exposure to poor nutrition in utero and overnutrition in later life in some populations, may contribute to the increasing diabetes epidemic through "diabetes begetting diabetes" in Asia. While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications, cancer is emerging as an important cause of morbidity and mortality. Type 2 diabetes is an increasing epidemic in Asia, characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index. Prevention and control of diabetes should be a top public health priority in Asian populations.


Corrugated round fibers to improve cell adhesion and proliferation in tissue engineering scaffolds.
Optimal cell interaction with biomaterial scaffolds is one of the important requirements for the development of successful in vitro tissue-engineered tissues. Fast, efficient and spatially uniform cell adhesion can improve the clinical potential of engineered tissue. Three-dimensional (3-D) solid free form fabrication is one widely used scaffold fabrication technique today. By means of deposition of polymer fibers, scaffolds with various porosity, 3-D architecture and mechanical properties can be prepared. These scaffolds consist mostly of solid round fibers. In this study, it was hypothesized that a corrugated fiber morphology enhances cell adhesion and proliferation and therefore leads to the development of successful in vitro tissue-engineered constructs. Corrugated round fibers were prepared and characterized by extruding poly(ethylene oxide terephthalate)-co-poly(butylene terephthalate) (300PEOT55PBT45) block co-polymer through specially designed silicon wafer inserts. Corrugated round fibers with 6 and 10 grooves on the fiber surface were compared with solid round fibers of various diameters. The culture of mouse pre-myoblast (C2C12) cells on all fibers was studied under static and dynamic conditions by means of scanning electron microscopy, cell staining and DNA quantification. After 7days of culturing under static conditions, the DNA content on the corrugated round fibers was approximately twice as high as that on the solid round fibers. Moreover, under dynamic culture conditions, the cells on the corrugated round fibers seemed to experience lower mechanical forces and therefore adhered better than on the solid round fibers. The results of this study show that the surface architecture of fibers in a tissue engineering scaffold can be used as a tool to improve the performance of the scaffold in terms of cell adhesion and proliferation.


Study of Ethanol-Induced Golgi Disorganization Reveals the Potential Mechanism of Alcohol-Impaired N-Glycosylation.
It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH-metabolism on the Golgi; however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH administration has on function of Golgi residential enzymes involved in N-glycosylation. HepG2 cells transfected with mouse ADH1 (VA-13 cells) were treated with 35 mM EtOH for 72 hours. Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Characterization of Golgi-associated mannosyl (α-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (MGAT1), α-1,2-mannosidase (Man-I), and α-mannosidase II (Man-II) were performed in VA-13 cells and rat hepatocytes followed by three-dimensional structured illumination microscopy (3D SIM). First, we detected that EtOH administration results in the loss of sialylated N-glycans on asialoglycoprotein receptor; however, the high-mannose-type N-glycans are increased. Further analysis by 3D SIM revealed that EtOH treatment despite Golgi disorganization does not change cis-Golgi localization for Man-I, but does induce medial-to-cis relocation of MGAT1 and Man-II. Using different approaches, including electron microscopy, we revealed that EtOH treatment results in dysfunction of ADP-ribosylation factor 1 (Arf1) GTPase followed by a deficiency in COPI vesicles at the Golgi. Silencing beta-COP or expression of GDP-bound mutant Arf1(T31N) mimics the EtOH effect on retaining MGAT1 and Man-II at the cis-Golgi, suggesting that (i) EtOH specifically blocks activation of Arf1, and (ii) EtOH alters the proper localization of Golgi enzymes through impairment of COPI. Importantly, the level of MGAT1 was reduced, because likely MGAT1, contrary to Man-I and Man-II, is giantin sensitive. Thus, we provide the mechanism by which EtOH-induced Golgi remodeling may significantly modify formation of N-glycans.


Mechanisms of recurrent atrial fibrillation: comparisons between segmental ostial versus circumferential pulmonary vein isolation.
Electrical isolation of pulmonary veins (PVs) is an effective therapy for atrial fibrillation (AF). Both segmental ostial PV ablation and circumferential ablation with PV-left atrial (LA) block have been implicated to eliminate AF. However, the mechanism of the recurrent AF after undergoing either strategy remains unclear. Of the 73 consecutive patients with symptomatic AF that underwent PV isolation and had recurrences of AF, Group 1 consisted of 46 patients (age 56 +/- 13 years old, 35 males) who underwent PV isolation by segmental ostial PV ablation and Group 2 consisted of 27 patients (age 51 +/- 11 years old, 24 males) who underwent circumferential ablation with PV-LA block. In Group 1, the earliest ectopic beat or ostial PV potentials were targeted. In Group 2, circumferential ablation with PV-LA block was performed by encircling the extraostial regions around the left and right PVs. During the first procedure, all patients had PV-AF. There was no difference in the non-PV ectopy between Group 1 and Group 2. During the second procedure, the incidence of an LA posterior wall ectopy initiating AF was significantly lower (20% vs. 0%, P = 0.01) in Group 2. There was no difference in the PV ectopy initiating AF during the second procedure. Circumferential ablation of AF with PV-LA block may eliminate the LA posterior wall ectopy and decrease the incidence of LA posterior wall ectopy initiating AF during the second procedure.


Physicians' communication and perceptions of patients: is it how they look, how they talk, or is it just the doctor?
Although physicians' communication style and perceptions affect outcomes, few studies have examined how these perceptions relate to the way physicians communicate with patients. Moreover, while any number of factors may affect the communication process, few studies have analyzed these effects collectively in order to identify the most powerful influences on physician communication and perceptions. Adopting an ecological approach, this investigation examined: (a) the relationships of physicians' patient-centered communication (informative, supportive, partnership-building) and affect (positive, contentious) on their perceptions of the patient, and (b) the degree to which communication and perceptions were affected by the physicians' characteristics, patients' demographic characteristics, physician-patient concordance, and the patient's communication. Physicians (N=29) and patients (N=207) from 10 outpatient settings in the United States participated in the study. From audio-recordings of these visits, coders rated the physicians' communication and affect as well as the patients' participation and affect. Doctors were more patient-centered with patients they perceived as better communicators, more satisfied, and more likely to adhere. Physicians displayed more patient-centered communication and more favorably perceived patients who expressed positive affect, were more involved, and who were less contentious. Physicians were more contentious with black patients, whom they also perceived as less effective communicators and less satisfied. Finally, physicians who reported a patient-centered orientation to the doctor-patient relationship also were more patient-centered in their communication. The results suggest that reciprocity and mutual influence have a strong effect on these interactions in that more positive (or negative) communication from one participant leads to similar responses from the other. Physicians' encounters with black patients revealed communicative difficulties that may lower quality of care for these patients.


A novel vaccine candidate against rabbit hemorrhagic disease virus 2 (RHDV2) confers protection in domestic rabbits.
To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits. 40 New Zealand White rabbits obtained from a commercial breeder. Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2. Rabbits were challenged with oral suspensions containing infectious virus and monitored for clinical disease for up to 10 days. Rabbits that died or were euthanized following infection were necropsied, and livers were evaluated for viral RNA via RT-PCR. None of the vaccinated animals (0/9) exhibited clinical disease or mortality following infection with RHDV2 while 9/13 (69%) of the control animals succumbed to lethal disease following infection. The novel vaccine described herein provided complete protection against lethal infection following RHDV2 challenge. Outside of emergency use, there are currently no licensed vaccines against RHDV2 on the market in the United States; as such, this vaccine candidate would provide an option for control of this disease now that RHDV2 has become established in North America.


Outpatient treatment of deep venous thrombosis in diverse inner-city patients.
We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis. Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment. The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient. This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.


Perceptual compensation is correlated with individuals' "autistic" traits: implications for models of sound change.
Variation is a ubiquitous feature of speech. Listeners must take into account context-induced variation to recover the interlocutor's intended message. When listeners fail to normalize for context-induced variation properly, deviant percepts become seeds for new perceptual and production norms. In question is how deviant percepts accumulate in a systematic fashion to give rise to sound change (i.e., new pronunciation norms) within a given speech community. The present study investigated subjects' classification of /s/ and // before /a/ or /u/ spoken by a male or a female voice. Building on modern cognitive theories of autism-spectrum condition, which see variation in autism-spectrum condition in terms of individual differences in cognitive processing style, we established a significant correlation between individuals' normalization for phonetic context (i.e., whether the following vowel is /a/ or /u/) and talker voice variation (i.e., whether the talker is male or female) in speech and their "autistic" traits, as measured by the Autism Spectrum Quotient (AQ). In particular, our mixed-effect logistic regression models show that women with low AQ (i.e., the least "autistic") do not normalize for phonetic coarticulation as much as men and high AQ women. This study provides first direct evidence that variability in human's ability to compensate for context-induced variations in speech perceptually is governed by the individual's sex and cognitive processing style. These findings lend support to the hypothesis that the systematic infusion of new linguistic variants (i.e., the deviant percepts) originate from a sub-segment of the speech community that consistently under-compensates for contextual variation in speech.


Clinical, biochemical and molecular analysis of 13 Japanese patients with β-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation [corrected].
β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant βUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, βUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human βUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that βUP deficiency is not as rare as generally considered and screening for βUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.


Percutaneous transluminal coronary angioplasty as a first revascularization procedure in single-, double- and triple-vessel coronary artery disease.
We sought to compare in-hospital and long-term outcome after angioplasty in patients with single-, double- and triple-vessel disease. Coronary angioplasty is increasingly used in patients with multivessel disease. The source of data was the clinical data base at Emory University. Patients who had previous coronary revascularization or who underwent angioplasty in the setting of acute myocardial infarction were excluded. Of 10,783 patients, 71% had one-vessel, 24% two-vessel and 5% three-vessel disease. Age, male gender, diabetes, hypertension, history of previous myocardial infarction, Canadian Cardiovascular Society class III or IV angina and congestive failure all increased with severity of disease. Complete revascularization was achieved in most patients with one-vessel disease, in a minority with two-vessel disease and rarely in those with three-vessel disease. Emergency coronary bypass surgery increased from 1.7% with one-vessel disease to 3.2% with three-vessel disease. Q wave myocardial infarctions could not be shown to vary significantly with severity of disease. The mortality rate increased from 0.2% with one-vessel disease to 1.2% with three-vessel disease. The number of vessels diseased was a multivariate correlate of in-hospital and long-term mortality. The 1-, 5- and 10-year survival was 0.99, 0.93 and 0.86 for one-vessel disease and 0.97, 0.89 and 0.76 for two-vessel disease, respectively. The 1-, 5- and 9-year survival was 0.95, 0.85 and 0.70 in three-vessel disease, respectively. Freedom from myocardial infarction, coronary bypass surgery and repeat angioplasty was also lower with more severe disease. Patients have increasing in-hospital and long-term mortality as the severity of disease increases. There is also an increased incidence of myocardial infarction and revascularization procedures with more severe disease.


Self-reported mental health of mothers with a school-aged child with a disability in Victoria: a mixed method study.
This research investigated the mental health of mothers of school-aged children with disabilities in Victoria, Australia. A mixed method triangulation design model was used to investigate the mental health of mothers (n= 152) of school-aged children with developmental disabilities. Self-reported medical history and completion of the Short Form Health Survey Version 2 were used to collect data via mail-out survey and follow-up phone interview. Mothers reported subjective mental health two standard deviations below other Australians and higher rates of depression and anxiety that other Australian women and the adult population in general. Half of participants reported that their health affected their ability to provide the care that their child needed, and half experienced frequent interrupted sleep secondary to the care of their child with a disability. Significantly poorer mental health was reported by mothers with a pre-school-aged child as well as a child with a disability (P < 0.001), mothers with more than one child with a disability (P= 0.038), mothers of children with autism spectrum disorder (ASD) (P= 0.026), and mothers who recognised that their health affected care giving (P < 0.001). The reported mental health of participants in this study indicates that further attention is needed to action health strategies to support mothers of children with disabilities. Health programs and policy that will identify mothers in need of assistance, as well as management strategies that will adequately support mental wellness in mothers is required in Australia.


The immediate effect of thumb orthoses on upper extremity's movement: A kinematic analysis of five unique devices.
Thumb orthoses are a standard treatment modality, with substantial evidence to support its usage for multiple conditions affecting the upper extremity. Despite commonly prescribed, little is known about the immediate impact of such devices on the upper extremity, including potential modifications on motor patterns. We aimed to determine the changes in the upper limb kinematics during the usage of thumb orthotics, comparing differences in orthotic design, length, and fabrication materials. In this cross-sectional study, subjects performed a standardized reaching task and the placing subtest of the Minnesota Manual Dexterity Test (MMDT) while wearing five unique thumb orthoses. Besides the active range of motion of the shoulder, elbow, wrist and hand joints, movement smoothness (Number of Movement Units-NMU), speed, and motion control strategies were analyzed through eight Qualisys Oqus 300 cameras (Qualisys AB, Göteborg, Sweden). Ten non-disabled, university students participated in this study. Despite differences in fabrication materials, all orthotics reduced thumb's abduction (13.3° to 4.3°), and metacarpophalangeal flexion (11.5° to 4.2°). Although orthotics impacted movement smoothness and hand function during its usage, forearm-based devices further increased the NMUs and the time required for the MMDT performance (Control: NMU = 4.8, MMDT = 58.1; Long Orthotics: NMU = 6.6, MMDT = 78.2), while short, flexible orthoses provided thumb stabilization without significant impact on upper extremity movement strategies. Although joint stabilization was similar among orthotics fabricated with rigid and flexible materials, the improved hand dexterity observed during the use of flexible devices suggests an advantage of flexible orthotics for enhanced stability and hand function. These results can assist healthcare professionals during the selection and prescription of thumb orthotics, providing information not only on the range of motion but other sensorimotor aspects involved in upper extremity movement patterns that may be affected by orthotics usage.


Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.
Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription. To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy. We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field. We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both). Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI). We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was difficult to assess possible reporting bias. We pooled 1070 participants from four RCTs to evaluate corporal atrophy development revealing an insignificantly increased OR of 1.50 (95% CI 0.59 to 3.80; P value = 0.39; low-quality evidence) for long-term PPI users relative to non-PPI users. In five eligible trials, corporal intestinal metaplasia was assessed among 1408 participants, also with uncertain results (OR 1.46; 95% CI 0.43 to 5.03; P value = 0.55; low-quality evidence). However, by pooling data of 1705 participants from six RCTs, our meta-analysis showed that participants with PPI maintenance treatment were more likely to experience either diffuse (simple) (OR 5.01; 95% CI 1.54 to 16.26; P value = 0.007; very-low-quality evidence) or linear/micronodular (focal) ECL hyperplasia (OR 3.98; 95% CI 1.31 to 12.16; P value = 0.02; low-quality evidence) than controls. No participant showed any dysplastic or neoplastic change in any included studies. There is presently no clear evidence that the long-term use of PPIs can cause or accelerate the progression of corpus gastric atrophy or intestinal metaplasia, although results were imprecise. People with PPI maintenance treatment may have a higher possibility of experiencing either diffuse (simple) or linear/micronodular (focal) ECL cell hyperplasia. However, the clinical importance of this outcome is currently uncertain.


Whole-body vibration exercise leads to alterations in muscle blood volume.
Occupationally used high-frequency vibration is supposed to have negative effects on blood flow and muscle strength. Conversely, low-frequency vibration used as a training tool appears to increase muscle strength, but nothing is known about its effects on peripheral circulation. The aim of this investigation was to quantify alterations in muscle blood volume after whole muscle vibration--after exercising on the training device Galileo 2000 (Novotec GmbH, Pforzheim, Germany). Twenty healthy adults performed a 9-min standing test. They stood with both feet on a platform, producing oscillating mechanical vibrations of 26 Hz. Alterations in muscle blood volume of the quadriceps and gastrocnemius muscles were assessed with power Doppler sonography and arterial blood flow of the popliteal artery with a Doppler ultrasound machine. Measurements were performed before and immediately after exercising. Power Doppler indices indicative of muscular blood circulation in the calf and thigh significantly increased after exercise. The mean blood flow velocity in the popliteal artery increased from 6.5 to 13.0 cm x s(-1) and its resistive index was significantly reduced. The results indicate that low-frequency vibration does not have the negative effects on peripheral circulation known from occupational high-frequency vibration.


[Trends in management, morbidity and mortality of patients with acute myocardial infarction hospitalized in the last decade].
The diagnosis and management of acute myocardial infarction (AMI) has undergone major changes during the last decade. These changes reflect the results of numerous controlled clinical trials that established the basis for evidence-based guidelines. The aims of this study were to examine the trends in the characteristics, management and outcome of patients with AMI, hospitalized in all 25 Intensive Care Units (ICCU) operating in Israel during the last decade (1994-2004). Data were derived from the biannual two-month national AMI/Acute Coronary Syndrome Israeli Surveys (ACSIS) performed in Israel. During the last decade, there was a continuous increase in the number of AMI patients admitted to the ICCU's operating in Israel - 999 AMI patients in 1994 and 1,534 in 2004. This increase was possibly due to shortening of hospital stay of AMI patients. The mean age of patients (64 years) did not change significantly in the last decade. The ICCU population has been characterized by an increasing number of octogenarians (7% in 1994 and 13% in 2004) and higher numbers of patients with past history of PCI, CABG, CVA and other comorbidities. There have been increases in the use of evidence-based medications during hospital stays and at discharge, reflecting greater adherence to guidelines. The "primary reperfusion" rate increased in the last decade from 60% in 1998 to 64% in 2004. The mode of reperfusion has changed in favor of primary PCI in 2004. In 1998, 88% of STEMI patients who underwent primary reperfusion were treated with thrombolysis and 12% by primary PCI while in 2004, 33% were treated with thrombolysis and 67% by primary PCI. The hospital course of patients with AMI in the last decade is characterized by better outcomes with reductions in rates of reischemia and reinfarction, cardiogenic shock, atrial fibrillation, VT/VF, and AV Block 2 degrees - 3 degrees. The most striking change in the last decade is the significant reduction in short- and long-term mortality with 45% reduction in 7-day mortality and 33% reduction in one-year mortality. This trend of better clinical outcomes and lower mortality in the last decade most probably relates to the use of evidence-based treatment and to better adherence to guidelines in the operating ICCUs in Israel.


Using Statistical Models of Morphology in the Search for Optimal Units of Representation in the Human Mental Lexicon.
Determining optimal units of representing morphologically complex words in the mental lexicon is a central question in psycholinguistics. Here, we utilize advances in computational sciences to study human morphological processing using statistical models of morphology, particularly the unsupervised Morfessor model that works on the principle of optimization. The aim was to see what kind of model structure corresponds best to human word recognition costs for multimorphemic Finnish nouns: a model incorporating units resembling linguistically defined morphemes, a whole-word model, or a model that seeks for an optimal balance between these two extremes. Our results showed that human word recognition was predicted best by a combination of two models: a model that decomposes words at some morpheme boundaries while keeping others unsegmented and a whole-word model. The results support dual-route models that assume that both decomposed and full-form representations are utilized to optimally process complex words within the mental lexicon.


Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens.
In 1972 there were only 11 genera and 26 species in the family Enterobacteriaceae. Today there are 22 genera, 69 species, and 29 biogroups or Enteric Groups. This paper is a review of all of the new organisms. It has a series of differential charts to assist in identification and a large chart with the reactions of 98 different organisms for 47 tests often used in identification. A simplified version of this chart gives the most common species and tests most often used for identification. The sources of the new organisms are listed, and their role in human disease is discussed. Fourteen new groups of Enterobacteriaceae are described for the first time. These new groups are biochemically distinct from previously described species, biogroups, and Enteric Groups of Enterobacteriaceae. The new groups are Citrobacter amalonaticus biogroup 1, Klebsiella group 47 (indole positive, ornithine positive), Serratia marcescens biogroup 1, and unclassified Enteric Groups 17, 45, 57, 58, 59, 60, 63, 64, 68, and 69.


Treating People With Epilepsy in Rural Low-Income Countries Is Feasible. Observations and Reflections From a "Real Life Experience" After a Long Lasting Intervention in the Rural Chaco.
Introduction: Epilepsy represents an important public health issue, in particular in low and middle-income countries where significant disparities are present in the care available for patients with epilepsy. Treatment cost and unavailability of drugs represent important barriers in treating people with epilepsy especially in rural setting. Aim of the study was to evaluate, by means of routine data, the current real-life clinical practice in epilepsy in the rural communities of the Plurinational State of Bolivia. Treatment activity followed educational campaigns and an anthropological fieldwork over more than 20 years. Material and Methods: Medical records of people with epilepsy (PWE) living in the rural communities of the Bolivian Chaco who received antiepileptic drugs (AEDs), from 2012 to 2016, and were followed-up for at least 1 year were analyzed. Treatment delivery and follow up visits were managed by a neurologist with the support of rural health care workers. Results: From 2012 to 2016, 157 PWE (76 men with a mean age of 24.2 ± 15.7) have been included in the study. Structural epilepsy was the most common type, recorded in 54 cases (34.4%) and the most common reported causes were perinatal factors, present in 11 subjects (20.0%). Almost all patients presented epilepsy with generalized tonic-clonic seizures (91.4%). The most common AED prescribed was phenobarbital followed by carbamazepine. During the follow-up, a dramatic seizures reduction was observed, with 31 subjects (19.7%) being seizures-free at the last follow-up. However, 48 subjects (30.6%) did not assume the medication regularly and 10 interrupted the drug intake. More than 20% of PWE did not receive any financial supports for AEDs. During the follow-up period 10 patients died but only in one case the death was probably caused by epilepsy. Conclusion: Our study demonstrated that PWE in rural areas of the Bolivian Chaco are willing to seek medical attention and to receive antiepileptic treatment. However, improvement in care is needed to assure compliance to AED treatment, including activity to increase awareness toward epilepsy among community members and health staff of the rural communities and to guarantee the coverage of treatment costs and drug supply.


Small GTP-binding protein, Rab6, is associated with secretory granules in atrial myocytes.
Rab proteins, a subfamily of small GTP-binding proteins, have been shown to play key roles in regulation of vesicular traffic in eukaryotic cells. In this study, we have intended to identify, the atrial granule-associated Rab proteins that seem to be required for formation or intracellular transport of the granules. Atrial granules contained at least four small GTP-binding proteins, and we have demonstrated by biochemical analysis that one of the small GTP-binding proteins associated with the atrial granules is a Rab6 protein (Rab6p). Rab6p was also detected in highly purified zymogen granules of pancreatic exocrine gland. Immunogold electron microscopy performed on ultrathin cryosections of rat auricle revealed that Rab6p was associated with the atrial granule membranes. Association of Rab6p with the atrial granule membranes was also confirmed by immunodiffusion electron microscopy in agarose-embedded atrial granules. These data indicate that Rab6p is associated with the atrial granules and that it might function in the intracellular traffic of the secretory granules in the atrial myocytes.


Methylene blue inhibits neurogenic cholinergic vasodilator responses in the pulmonary vascular bed of the cat.
The effects of methylene blue, an inhibitor of soluble guanylate cyclase, on pulmonary vasodilator responses to efferent vagal stimulation were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. In animals pretreated with reserpine or phenoxybenzamine, under elevated tone conditions, efferent vagal stimulation at frequencies of 2-16 Hz caused stimulus-frequency-dependent decreases in lobar arterial pressure and pulmonary lobar vascular resistance. The vasodilator response to vagal stimulation was reproducible, blocked by atropine, and reduced by methylene blue. Intralobar infusion of methylene blue increased lobar arterial pressure without significantly altering systemic arterial or left atrial pressure. Methylene blue had no significant effect on vasodilator responses to isoproterenol, albuterol, atriopeptin III, lemakalim, adenosine, ATP, and pituitary adenylate cyclase-activating polypeptide-27 but significantly decreased vasodilator responses to acetylcholine, nitric oxide (NO), sodium nitroprusside, and the S-nitrosothiol, S-nitroso-N-acetyl-penicillamine. The effects of methylene blue on responses to vagal stimulation were reversible and were similar with the addition of a NO synthase inhibitor. The present data suggest that vasodilator responses to cholinergic nerve stimulation involve an increase in the production of guanosine 3',5'-cyclic monophosphate in the pulmonary vascular bed. These results provide additional evidence to support the hypothesis that neurogenically released acetylcholine induces endothelium-dependent, muscarinic, guanylate cyclase-mediated vasodilation.


Accuracy in detecting inadequate research reporting by early career peer reviewers using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process: a cross-sectional diagnostic study.
The peer review process has been questioned as it may fail to allow the publication of high-quality articles. This study aimed to evaluate the accuracy in identifying inadequate reporting in RCT reports by early career researchers (ECRs) using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process. We performed a cross-sectional diagnostic study of 119 manuscripts, from BMC series medical journals, BMJ, BMJ Open, and Annals of Emergency Medicine reporting the results of two-arm parallel-group RCTs. One hundred and nineteen ECRs who had never reviewed an RCT manuscript were recruited from December 2017 to January 2018. Each ECR assessed one manuscript. To assess accuracy in identifying inadequate reporting, we used two tests: (1) ECRs assessing a manuscript using the COBPeer tool (after completing an online training module) and (2) the usual peer-review process. The reference standard was the assessment of the manuscript by two systematic reviewers. Inadequate reporting was defined as incomplete reporting or a switch in primary outcome and considered nine domains: the eight most important CONSORT domains and a switch in primary outcome(s). The primary outcome was the mean number of domains accurately classified (scale from 0 to 9). The mean (SD) number of domains (0 to 9) accurately classified per manuscript was 6.39 (1.49) for ECRs using COBPeer versus 5.03 (1.84) for the journal's usual peer-review process, with a mean difference [95% CI] of 1.36 [0.88-1.84] (p < 0.001). Concerning secondary outcomes, the sensitivity of ECRs using COBPeer versus the usual peer-review process in detecting incompletely reported CONSORT items was 86% [95% CI 82-89] versus 20% [16-24] and in identifying a switch in primary outcome 61% [44-77] versus 11% [3-26]. The specificity of ECRs using COBPeer versus the usual process to detect incompletely reported CONSORT domains was 61% [57-65] versus 77% [74-81] and to identify a switch in primary outcome 77% [67-86] versus 98% [92-100]. Trained ECRs using the COBPeer tool were more likely to detect inadequate reporting in RCTs than the usual peer review processes used by journals. Implementing a two-step peer-review process could help improve the quality of reporting. Clinical.Trials.gov NCT03119376 (Registered April, 18, 2017).


A predictive network model of cerebral cortical connectivity based on a distance rule.
Recent advances in neuroscience have engendered interest in large-scale brain networks. Using a consistent database of cortico-cortical connectivity, generated from hemisphere-wide, retrograde tracing experiments in the macaque, we analyzed interareal weights and distances to reveal an important organizational principle of brain connectivity. Using appropriate graph theoretical measures, we show that although very dense (66%), the interareal network has strong structural specificity. Connection weights exhibit a heavy-tailed lognormal distribution spanning five orders of magnitude and conform to a distance rule reflecting exponential decay with interareal separation. A single-parameter random graph model based on this rule predicts numerous features of the cortical network: (1) the existence of a network core and the distribution of cliques, (2) global and local binary properties, (3) global and local weight-based communication efficiencies modeled as network conductance, and (4) overall wire-length minimization. These findings underscore the importance of distance and weight-based heterogeneity in cortical architecture and processing.


A government sponsored clinic for the evaluation and treatment of chronic hepatitis C in an underinsured population in Puerto Rico.
Chronic hepatitis C (CHC) is a major health problem in Puerto Rico (PR). More than 50% of the population is insured by a government-sponsored managed care system that does not cover treatment for CHC. Lack of access to treatment will result in an increase in end-stage liver disease with its high socioeconomic impact in the future. In an attempt to identify strategies for the treatment of CHC in the publicly insured population, the PR Health Department and the University of Puerto Rico (UPR) Gastroenterology (GI) Division have developed a pilot clinic for the evaluation and treatment of CHC. UPR and the PR Health Department negotiated a fee per patient to include all medical care and follow-up laboratories. Viral studies were covered by a grant to the Health Department. Medications were bought at a discount price by the government and dispensed at a government pharmacy. The Health Department allocated funds for 200 patients with government insurance. A dedicated clinic was established at the UPR, staffed by an internist under the supervision of the GI faculty. Patients with a positive HCVab were referred to this clinic. The public insurance covered the CBC, liver tests, metabolic panel, TSH, HBsAg, HIV, ultrasound and liver biopsy, which were required prior to evaluation for possible treatment. In the initial visit, patients underwent a medical evaluation, including assessment of suitability for therapy and counseling. Those deemed to be candidates who still needed a liver biopsy had it performed by the GI staff. Genotype and viral titers were ordered after the decision on treatment had been made. The clinic physician prescribed pegylated interferon and ribavirin, which were dispensed by the government pharmacy. Instruction on proper drug administration was given. Clinic visits were scheduled for 1, 3, 6 and 12 months but also allowed on demand. Laboratory tests were done at the clinic and reviewed by the physician expediently to monitor for toxicity. Any medical problems or treatment for complications of therapy were covered by the primary insurer. Viral load was repeated at 12 weeks to discontinue therapy in those unlikely to respond. The budget per patient for medical visits and laboratory tests was dollars 1,500.00, HCV RNA titers plus genotype costs dollars 200.00, and HCV qualitative RNA costs dollars 123.00 405 patients have been referred between February 2002 and April 2003 (the number was increased at adjust for no-shows and those not treated). 30% are female, the major risk factor is IVDU, and 80% are unemployed. 101 have started treatment and 48 are awaiting biopsy. A support group has been established at the clinic. The treatment for CHC in practice is not only costly but also resource consuming. Most gastroenterologists in our community refer these patients for treatment. The establishment of a dedicated clinic with a primary physician supervised by the specialists reduces costs and facilitates caring for a larger number of patients. The volume of services allows for negotiation of medical, laboratory and drug costs. In allocating funds for this project, the PR Health Department recognized the importance in reducing the potential spread in the community by treating infected patients as well as reducing the future medical and socioeconomic burden of end-stage liver disease. Although the outcome of this project is still unseen, we believe that this model may serve to establish other clinics for the treatment of CHC at lower costs with the same effectiveness.


Cell type-specific protein and transcription profiles implicate periarbuscular membrane synthesis as an important carbon sink in the mycorrhizal symbiosis.
The development of an arbuscular mycorrhizal (AM) symbiosis is a non-synchronous process with typical mycorrhizal root containing different symbiotic stages at one time. Methods providing cell type-specific resolution are therefore required to separate these stages and analyze each particular structure independently from each other. We established an experimental system for analyzing specific proteomic changes in arbuscule-containing cells of Glomus intraradices colonized Medicago truncatula roots. The combination of laser capture microdissection (LCM) and liquid chromatography-tandem mass chromatography (LC-MS/MS) allowed the identification of proteins with specific or increased expression in arbuscule-containing cells. Consistent with previous transcriptome data, the proteome of arbuscule-containing cells showed an increased number of proteins involved in lipid metabolism, most likely related to the synthesis of the periarbuscular membrane. In addition, transcriptome data of non-colonized cells of mycorrhizal roots suggest mobilization of carbon resources and their symplastic transport toward arbuscule-containing cells for the synthesis of periarbuscular membranes. This highlights the periarbuscular membrane as important carbon sink in the mycorrhizal symbiosis.


MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function.
Chromosomal rearrangements associated with acute myeloid leukemia (AML) include fusions of the genes encoding the acetyltransferase MOZ or MORF with genes encoding the nuclear receptor coactivator TIF2, p300, or CBP. Here we show that MOZ-TIF2 acts as a dominant inhibitor of the transcriptional activities of CBP-dependent activators such as nuclear receptors and p53. The dominant negative property of MOZ-TIF2 requires the CBP-binding domain (activation domain 1 [AD1]), and coimmunoprecipitation and fluorescent resonance energy transfer experiments show that MOZ-TIF2 interacts with CBP directly in vivo. The CBP-binding domain is also required for the ability of MOZ-TIF2 to extend the proliferative potential of murine bone marrow lineage-negative cells in vitro. We show that MOZ-TIF2 displays an aberrant nuclear distribution and that cells expressing this protein have reduced levels of cellular CBP, leading to depletion of CBP from PML bodies. In summary, our results indicate that disruption of the normal function of CBP and CBP-dependent activators is an important feature of MOZ-TIF2 action in AML.


Evolution of leaf developmental mechanisms.
Leaves are determinate organs produced by the shoot apical meristem. Land plants demonstrate a large range of variation in leaf form. Here we discuss evolution of leaf form in the context of our current understanding of leaf development, as this has emerged from molecular genetic studies in model organisms. We also discuss specific examples where parallel studies of development in different species have helped understanding how diversification of leaf form may occur in nature.


[A case of Fournier's gangrene reconstructed using a rectus abdominis muscle flap].
We encountered a case of Fournier's gangrene complicated with vesicorectocutaneous fistula that was treated with a pedicled rectus abdominis muscle flap (pedicled RA m-c flap). A 75-year-old man was admitted with consciousness disorder and swelling of the scrotum. The patient had noticed swelling of the scrotum 4 days before admission, but he had ignored this condition. The scrotum and the penis appeared necrotic. On the basis of clinical and radiological findings, we diagnosed this condition as Fournier's gangrene. Surgical debridement was performed in conjunction with the use of broad-spectrum antibiotics. After the patient's general condition was improved, the broad defect in the perineal tissue was covered with a pedicled rectus abdominis muscle flap. The flap was successful. In Japan, this is the first case of Fournier's gangrene complicated with vesicorectocutaneous fistula that was treated with a pedicled RA m-c flap. In order to determine whether plastic surgery after debridement shortens the duration of hospitalization, we reviewed the cases of 120 patients with Fournier's gangrene in Japan. We conclude that plastic surgery after debridement does not shorten the duration of hospitalization, however, this procedures is very useful to deep and broad defects by Fournier's gangrene.


Physical Activity Is Associated With Greater Visuospatial Cognitive Functioning Regardless of the Level of Cognitive Load in Elderly Adults.
The study aimed to investigate the effects of regular physical activity on visuospatial cognition in elderly adults, and to further understand the potential neural mechanisms underpinning such effects. We assessed 24 physically active elderly adults and 24 sedentary counterparts using behavioral and neuroelectric measures during a visuospatial cognitive task with different levels of cognitive load. The results showed that the active group had higher behavioral accuracy along with greater P3 amplitudes, regardless of the level of cognitive load. Moreover, the correlation results revealed that physical activity levels were positively associated with accuracy performance in both conditions, while being correlated with frontal P3 amplitudes in the high cognitively demanding condition. However, no significant effects were observed in terms of P3 latency and contingent negative variation. These findings suggest that regular physical activity might be part of an effective lifestyle to attenuate the trajectory of age-related cognitive declines, thus increasing the likelihood of individuals becoming high-functioning older adults.


Controlled single-photon emission from a single trapped two-level atom.
By illuminating an individual rubidium atom stored in a tight optical tweezer with short resonant light pulses, we created an efficient triggered source of single photons with a well-defined polarization. The measured intensity correlation of the emitted light pulses exhibits almost perfect antibunching. Such a source of high-rate, fully controlled single-photon pulses has many potential applications for quantum information processing.


Contact, high-resolution spatial diffuse reflectance imaging system for skin condition diagnosis: a first-in-human clinical trial.
Oxygenation is one of the skin tissue physiological properties to follow for patient care management. Furthermore, long-term monitoring of such parameters is needed at the patient bed as well as outside the hospital. Diffuse reflectance spectroscopy has been widely used for this purpose. The aim of the study is to propose a low-cost system for the long-term measurement of skin physiological parameters in contact. We have developed a low-cost, wearable, CMOS-based device. We propose an original method for processing diffuse reflectance data to calculate the tissue oxygen saturation (StO2). We tested the device for the assessment of tissue oxygenation during a first-in-human clinical trial that took place at the Grenoble University Hospital France. The results of this clinical trial show a good accordance between our sensor and commercial devices used a reference.


Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.
There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.


Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection.
Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle.


Evaluation of renal lesions and clinicopathologic correlation in rheumatoid arthritis.
The most common causes of renal disease in rheumatoid arthritis (RA) are glomerulonephritis (GN), amyloidosis, tubulo-interstitial nephritis, and drug toxicity. Our aim was to evaluate the clinicopathologic correlation of renal lesions and to assess the course and prognosis of renal disease in patients with RA. We conducted a prospective observational study in all adult patients with RA between July 2010 and June 2015. The total number of patients studied was 90, with a female:male ratio of 2.3:1. Mean follow-up duration was 30 ± 6.5 months. About 54 patients (60%) were asymptomatic. The most common symptom was edema legs (30%), followed by oliguria (10%). About 18 patients (20%) presented with the nephrotic syndrome, 15 patients (16.6%) with nephritic syndrome, and 30 (33%) with asymptomatic urinary abnormalities. Chronic kidney disease (CKD) was seen in 48 of 90 patients (53%).The most common renal pathology noted was mesangioproliferative GN followed by membranous nephropathy (MN). IgM with C3 deposits was the most common immunofluorescence pattern observed. Among the patients who had glomerular diseases, complete remission was seen in nine patients, partial remission in 15, and persistent proteinuria in 14. Duration of RA and a high erythrocyte sedimentation rate correlated significantly with persistent proteinuria. Only one patient in the glomerular disease group progressed to dialysis-dependent renal failure. On followup, 11 out of 48 CKD patients showed a significant decrease in estimated glomerular filtration rate and worsened to the next stage of CKD. Renal disease in RA presents with varied renal pathology. MN was seen frequently and was not associated with gold or penicillamine usage. Relatively high incidence of CKD was noted. Hence, it is important to monitor renal function abnormalities periodically in these patients.


Characterization of T cells expressing the gamma/delta antigen receptor in human renal allografts.
To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (> 10% of the total T-cell population) with gamma/delta+ T cells. No biopsies from nonrejecting kidneys showed > 10% gamma/delta+ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (> 10%) of gamma/delta+ T cells. Six cell lines with increased numbers of gamma/delta+ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively alpha/beta T-cell populations. Lysis was noted by all gamma/delta+, but no gamma/delta-, populations. To confirm that the cytotoxicity of these gamma/delta+ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% gamma/delta+ T cells by cytometry and > 50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen-expressing targets were not killed. Sterile cell sorting was used to isolate the gamma/delta+ T cells. The gamma/delta+ cells displayed enhanced killing of K562 while the gamma/delta- cells showed no cytolytic activity. Cytotoxicity mediated by gamma/delta+ T cells was also demonstrated against donor-derived, untransformed renal cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Developmental dynamics between reading and math in elementary school.
Reading and math attainment develop during elementary grades. Questions remain, though, about the co-developmental nature of the relation between reading and math. This study examined dynamic, longitudinal pathways between reading and math in first through fourth grades. Participants of the study were 554 academically at-risk children (Mage at the first assessment point = 6.57 years; SD = 0.38) from Texas Project Achieve. Children were assessed utilizing the Woodcock-Johnson-III reading and math measures. Results from dynamic bivariate latent change score models indicated unidirectional longitudinal coupling effects from reading to math. Specifically, average and high levels of reading performance were associated with subsequent gains in math growth, in particular for below average performing children in math. In contrast, low levels of reading performance had negligible or no amplifying influences on change in math growth. The nature of the dynamics was replicated even when controlling for nonverbal cognitive abilities. Results demonstrated that good reading skills pave the way for children to develop their math skills. Such findings underscore the importance of considering reading performance in treating math difficulties.


Features of optical coherence tomography predictive of choroidal neovascularisation treatment response in pathological myopia in association with fluorescein angiography.
The aim of this study was to evaluate the usefulness of several optical coherence tomography (OCT) findings to estimate choroidal neovascularisation (CNV) activity in pathological myopia using fluorescein angiography (FA) as a reference. This was a single-centre, retrospective study. The medical records of patients with active myopic CNV who received intravitreal bevacizumab treatment were reviewed. Parameters to monitor CNV activity were morphological features of CNV on OCT, such as CNV height, central foveal thickness, intraretinal cysts, subretinal fluid, fuzziness of the CNV border, CNV network area on FA, and haemorrhage or exudation on fundus photo. There were 46 patients with active CNV enrolled in this study. After intravitreal bevacizumab treatment, all the previously mentioned parameters of CNV were significantly improved. Using logistic regression analyses with backward elimination, the fuzzy border seen on OCT showed the most significant correlation with improvement of leakage on FA, when compared with other variables such as intraretinal cysts, subretinal fluid or central foveal thickness (R2=0.324, p=0.009). Our study showed that the fuzziness of the hyper-reflective CNV margin showed the most significant improvement and the strongest correlation with the improvement of CNV leakage on FA after intravitreal bevacizumab injections, suggesting its important role as an OCT parameter for the assessment of myopic CNV activity.


Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines.
Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial⁻mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs. However, the VHL status alone cannot predict the differential sensitivity of ccRCC to cancer treatments, which suggests that other molecular differences may contribute to the differential response of ccRCC cells to drug therapies. In this study, we investigated the response to metformin (an antidiabetic drug) of two human ccRCC cell lines Caki-1 and Caki-2, which express wild-type VHL. Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL. Our study unveils the therapeutic potential of metformin to inhibit the progression of ccRCC in vitro. Additional preclinical and clinical studies are required to ascertain the therapeutic efficacy of metformin against ccRCC.


Cryotolerance of porcine in vitro-produced blastocysts relies on blastocyst stage and length of in vitro culture prior to vitrification.
The aim of our study was to assess whether the cryotolerance of in vitro-produced embryos could be influenced by the length of in vitro culture and size of blastocoel cavity before vitrification, using the pig as a model. For this purpose we analysed the cryoresistance and apoptosis rate of blastocysts at different stages of development as derived on Day 5 and 6 of in vitro culture. Blastocysts were subsequently vitrified, warmed and cultured for 24h. Re-expansion rates were recorded at 3 and 24h and total cell number and apoptotic cells were determined at 24h. Day-6 blastocysts showed the highest rates of survival after warming, which indicates higher quality compared with Day-5 blastocysts. Higher re-expansion rates were observed for expanded blastocysts and those in the process of hatching when compared with early blastocysts. Total cell number and apoptotic cells were affected by blastocyst stage, vitrification-warming procedures and length of in vitro culture, as expanding and hatching-hatched blastocysts from Day 6 presented higher percentages of apoptotic cells than fresh blastocysts and blastocysts vitrified at Day 5. Our findings suggest that the cryotop vitrification method is useful for the cryopreservation of porcine blastocysts presenting a high degree of expansion, particularly when vitrification is performed after 6 days of in vitro culture. Furthermore, these results show that faster embryo development underlies higher blastocyst cryotolerance and provide evidence that blastocoel cavity expansion before vitrification is a reliable index of in vitro-produced embryo quality and developmental potential.


Time-dependent theoretical model for terahertz wave detector using a parametric process.
We have presented a time-dependent theoretical model to describe the time behavior of a quasi-monochromatic nanosecond terahertz detector reported by Guo et al. [Appl. Phys. Lett. 93, 021106 (2008)]. The temporal input-output characteristic of the detector is investigated numerically by taking the system parameters close to the experimental ones, and the calculated pulse width for the incident terahertz wave agrees well with the experimental one. Our results demonstrate that the energy and width of an output idler wave pulse are proportional to those of the incident terahertz wave pulse. This study provides a strict theoretical basis and could be used to guide the design and optimization for the highly sensitive coherent terahertz detector.


CHIP-ping away at tau.
Protein accumulation is a hallmark of many neurodegenerative disorders. In Alzheimer's disease (AD), a hyperphosphorylated form of the protein tau (p-tau) forms intracellular inclusions known as neurofibrillary tangles. Deposits of p-tau have also been found in the brains of patients with Down's syndrome, supranuclear palsy, and prion disease. Mutations in tau have been causally associated with at least one inherited neurologic disorder, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), implying that tau abnormalities by themselves can be a primary cause of degenerative diseases of the CNS. Removal of these p-tau species may occur by both chaperone-mediated refolding and degradation. In this issue of the JCI, Dickey and colleagues show that a cochaperone protein, carboxyl terminus of Hsp70-interacting protein (CHIP), in a complex with Hsp90 plays an important role in the removal of p-tau (see the related article beginning on page 648). Pharmacologic manipulation of Hsp90 may be used to alleviate p-tau accumulation in disease.


Dissemination of imipenem-resistant Acinetobacter baumannii with new plasmid-borne bla(OXA-72) in Taiwan.
The systemic surveillance of imipenem-resistant Acinetobacter baumannii (IRAB) from multicenters in Taiwan revealed the emergence of isolates with bla(OXA-72). This study described their genetic makeup, mechanism of spread, and contribution to carbapenem resistance. Two hundred and ninety-one non-repetitive isolates of A. baumannii were collected from 10 teaching hospitals from different geographical regions in Taiwan from June 2007 to September 2007. Minimal inhibitory concentrations (MICs) were determined by agar dilution. Clonality was determined by pulsed-field gel electrophoresis. Plasmid was extracted and digested by restriction enzymes, and subsequently analyzed by electrophoresis and Southern blot for bla(OXA-72). The flanking regions of bla(OXA-72) were determined by inverse PCR. The contribution of bla(OXA-72) to imipenem MIC was determined by transforming plasmids carrying bla(OXA-72) into imipenem-susceptible A. baumannii. Among 142 IRAB in Taiwan, 27 harbored bla(OXA-72); 22 originated from Southern Taiwan, 5 from Central Taiwan, and none from Northern Taiwan. There were two major clones. The bla(OXA-72) was identified in the plasmids of all isolates. Two genetic structures flanking plasmid-borne bla(OXA-72) were identified and shared identical sequences in certain regions; the one described in previous literature was present in only one isolate, and the new one was present in the remaining isolates. Introduction of bla(OXA-72) resulted in an increase of imipenem MIC in the transformants. The overexpression of bla(OXA-72) mRNA in response to imipenem further supported the contribution of bla(OXA-72). In conclusion, isolates with new plasmid-borne blaOXA-72 were found to be disseminated successfully in Southern Taiwan. The spread of the resistance gene depended on clonal spread and dissemination of a new plasmid. Bla(OXA-72) in these isolates directly led to their imipenem-resistance.


Deglycosylated anti-amyloid beta antibodies reduce microglial phagocytosis and cytokine production while retaining the capacity to induce amyloid beta sequestration.
Accumulation of amyloid beta (Abeta) is a pathological hallmark of Alzheimer's disease, and lowering Abeta is a promising therapeutic approach. Intact anti-Abeta antibodies reduce brain Abeta through two pathways: enhanced microglial phagocytosis and Abeta transfer from the brain to the periphery (Abeta sequestration). While activation of microglia, which is essential for microglial phagocytosis, is necessarily accompanied by undesired neuroinflammatory events, the capacity for sequestration does not seem to be linked to such effects. We and other groups have found that simple Abeta binding agents are sufficient to reduce brain Abeta through the sequestration pathway. In this study, we aimed to eliminate potentially deleterious immune activation from antibodies without affecting the ability to induce sequestration. The glycan portion of immunoglobulin is critically involved in interactions with immune effectors including the Fc receptor and complement c1q; deglycosylation eliminates these interactions, while antigen (Abeta)-binding affinity is maintained. In this study, we investigated whether deglycosylated anti-Abeta antibodies reduce microglial phagocytosis and neuroinflammation without altering the capacity to induce Abeta sequestration. Deglycosylated antibodies maintained Abeta binding affinity. Deglycosylated antibodies did not enhance Abeta phagocytosis or cytokine release in primary cultured microglia, whereas intact antibodies did so significantly. Intravenous injection of deglycosylated antibodies elevated plasma Abeta levels and induced Abeta sequestration to a similar or greater degree compared with intact antibodies in an Alzheimer's transgenic mouse model without or with Abeta plaque pathology. We conclude that deglycosylated antibodies effectively induced Abeta sequestration without provoking neuroinflammation; thus, these deglycosylated antibodies may be optimal for sequestration therapy for Alzheimer's disease.


Cold immersion recovery responses in the diabetic foot with neuropathy.
The aim of this article was to investigate the effectiveness of testing cold immersion recovery responses in the diabetic foot with neuropathy using a contact thermography system based on thermochromic liquid crystals. A total of 81 subjects with no history of diabetic foot ulceration were assigned to neuropathy, non neuropathy and healthy groups. Each group received prior verbal and written description of the test objectives and subsequently underwent a comprehensive foot care examination. The room temperature and humidity were consistently maintained at 24 degrees C and less than 50%, respectively, with air conditioning. The right foot for each subject was located on the measurement platform after cold immersion in water at 18-20 degrees C. Whole-field thermal images of the plantar foot were recorded for 10 minutes. Patients with diabetes with neuropathy show the highest 'delta temperature', that is difference between the temperature after 10-minute recovery period and baseline temperature measured independently at all the three sites tested, that is first metatarsal head (MTH), second MTH and heel. This clinical study showed for the first time the evidence of poor recovery times for the diabetic foot with neuropathy when assessing the foot under load. A temperature deficit (because of poor recovery to baseline temperature) suggests degeneration of thermoreceptors, leading to diminished hypothalamus-mediated activity in the diabetic neuropathic group.


Alpaca semen characteristics previous to a mating period.
Increasing the knowledge of the semen characteristics in the alpaca will contribute to understanding one of the many factors that affect the poor fertility rate in this species. Ten adult male alpacas, 2.6-10 years of age, average weight 64.7 +/- 4.7 kg were used. The animals were distributed randomly into two groups of five each and submitted alternatively to two semen collections, using an artificial vagina and sexually receptive females. For the first semen collection the animals had a sexual rest period of about 90 and 45 days before the second. Duration of semen collection, color and volume of ejaculate were recorded, and sperm concentration and morphology (light microscopy) were evaluated. Descriptive statistical analyses were used for each variable, considering all samples obtained (n= 19). An analysis of variance for animal groups and opportunity of collection were used for quantitative variables. Most frequent color was opalescent white (84.2%). There were no statistical differences among male groups or between semen collections. The average values and standard deviations for the quantitative variables were: 12.3 +/- 7.2 min for semen collection time, 1.8 +/- 0.8 ml for ejaculate volume, (17.6 +/- 26.1) x 10(6) sperm/ml for sperm concentration and 34.0 +/- 52.2 x 10(6) for total number of sperm per ejaculate. The percentage of normal spermatozoa was 51.0 +/- 12.4%. From the total abnormalities, that of mid piece segment (14.4%) was the most frequent. These results indicate that male alpaca have poor semen quality, when compared with other domestic species. Nevertheless, for the evaluation of male alpaca as breeders it would be necessary to create a protocol for the selection of them, where phenotypic, behavioral and seminogram aspects are considered. The values reported herein define the characteristics of the alpaca semen that could be considered as the initial base of the seminal analysis to select male alpacas before mating.


T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis infection.
Young children exposed to tuberculosis have a high risk of progression to severe tuberculosis disease, but diagnosis of recent infection is hindered by the poor sensitivity of the tuberculin skin test. Whether new blood tests can detect latent infection in this vulnerable group is unknown because there is no gold standard. We monitored a tuberculin skin test-negative infant whose mother had infectious multidrug-resistant tuberculosis with enzyme-linked immunospot, a blood test that enumerates Mycobacterium tuberculosis-specific T cells. The enzyme-linked immunospot test became persistently positive by 6 months, and 18 months later the child developed active tuberculosis despite appropriate chemoprophylaxis. At this point, the magnitude of the enzyme-linked immunospot response increased >10-fold. Our findings demonstrate that this blood test detected latent infection with dormant, yet viable, bacilli and illustrate how enzyme-linked immunospot could improve diagnosis of childhood tuberculosis infection.