BCL-2 expression and mitochondrial activity in leukemic cells with different sensitivity to glucocorticoid-induced apoptosis.
The present study investigates the relationship between mitochondrial activity and the expression of the BCL-2 gene in a panel of six human and murine leukemia/lymphoma cell lines. The cell lines all contained normal glucocorticoid receptors but differed widely in sensitivity to dexamethasone, ranging from very sensitive S49 lymphoma to completely resistant HL-60 acute leukemia cells. In this panel, 10- to 15-fold differences in basal adenosine triphosphate (ATP) content and adenosine diphosphate (ADP)/ATP ratio were correlated with up to fivefold differences in bcl-2 protein (in human cells) and approximately 25-fold difference in bcl-2 mRNA content (all cell lines). Moreover, ATP content and BCL-2 gene expression were inversely correlated with glucocorticoid sensitivity and cell cycle length. In resistant cell lines, sensitivity to dexamethasone was restored by the mitochondrial inhibitors rotenone and meta-iodobenzylguanidine. This sensitization was not accompanied by detectable reductions in bcl-2 mRNA or protein content, suggesting that the inhibitors were capable of overriding BCL-2-mediated inhibition of apoptosis. Increased mitochondrial activity and (overexpressed) BCL-2 appeared closely related properties of glucocorticoid-resistant cells, sharing common cellular targets in hormone-induced apoptosis.


Neuronal activity in the primate motor thalamus during visually triggered and internally generated limb movements.
Single-unit recordings were made from the basal-ganglia- and cerebellar-receiving areas of the thalamus in two monkeys trained to make arm movements that were either visually triggered (VT) or internally generated (IG). A total of 203 neurons displaying movement-related changes in activity were examined in detail. Most of these cells (69%) showed an increase in firing rate in relation to the onset of movement and could be categorized according to whether they fired in the VT task exclusively, in the IG task exclusively, or in both tasks. The proportion of cells in each category was found to vary between each of the cerebellar-receiving [oral portion of the ventral posterolateral nucleus (VPLo) and area X] and basal-ganglia-receiving [oral portion of the ventral lateral nucleus (VLo) and parvocellular portion of the ventral anterior nucleus (VApc)] nuclei that were examined. In particular, in area X the largest group of cells (52%) showed an increase in activity during the VT task only, whereas in VApc the largest group of cells (53%) fired in the IG task only. In contrast to this, relatively high degree of task specificity, in both VPLo and VLo the largest group of cells ( approximately 55%) burst in relation to both tasks. Of the cells that were active in both tasks, a higher proportion were preferentially active in the VT task in VPLo and area X, and the IG task in VLo and VApc. In addition, cells in all four nuclei became active earlier relative to movement onset in the IG task compared with the VT task. These results demonstrate that functional distinctions do exist in the cerebellar- and basal-ganglia-receiving portions of the primate motor thalamus in relation to the types of cues used to initiate and control movement. These distinctions are most clear in area X and VApc, and are much less apparent in VPLo and VLo.


A composite metric for assessing data on mortality and causes of death: the vital statistics performance index.
Timely and reliable data on causes of death are fundamental for informed decision-making in the health sector as well as public health research. An in-depth understanding of the quality of data from vital statistics (VS) is therefore indispensable for health policymakers and researchers. We propose a summary index to objectively measure the performance of VS systems in generating reliable mortality data and apply it to the comprehensive cause of death database assembled for the Global Burden of Disease (GBD) 2013 Study. We created a Vital Statistics Performance Index, a composite of six dimensions of VS strength, each assessed by a separate empirical indicator. The six dimensions include: quality of cause of death reporting, quality of age and sex reporting, internal consistency, completeness of death reporting, level of cause-specific detail, and data availability/timeliness. A simulation procedure was developed to combine indicators into a single index. This index was computed for all country-years of VS in the GBD 2013 cause of death database, yielding annual estimates of overall VS system performance for 148 countries or territories. The six dimensions impacted the accuracy of data to varying extents. VS performance declines more steeply with declining simulated completeness than for any other indicator. The amount of detail in the cause list reported has a concave relationship with overall data accuracy, but is an important driver of observed VS performance. Indicators of cause of death data quality and age/sex reporting have more linear relationships with simulated VS performance, but poor cause of death reporting influences observed VS performance more strongly. VS performance is steadily improving at an average rate of 2.10% per year among the 148 countries that have available data, but only 19.0% of global deaths post-2000 occurred in countries with well-performing VS systems. Objective and comparable information about the performance of VS systems and the utility of the data that they report will help to focus efforts to strengthen VS systems. Countries and the global health community alike need better intelligence about the accuracy of VS that are widely and often uncritically used in population health research and monitoring.


Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review.
Depression is one of the most common psychiatric disorders, and the fourth leading cause of long-term disability throughout the world. Despite the availability of different classes of antidepressant drugs, most of them are not completely effective and above all are associated with many serious adverse effects. Recently, accumulating evidence suggests that dietary supplements rich in important phytochemicals possess beneficial therapeutic roles in depression. In this review, we will first consider what is known about the pathogenesis of depression and discuss the need for more safe and efficacious treatment. We will then review the potential clinical relevance of natural plant-derived products based on data derived from pre-clinical animal studies, randomized controlled studies and placebo-controlled trials published on this topic within the last decade. Among the natural compounds that show antidepressive-like activity, green tea catechins have been shown to decrease depressive symptoms in experimental animals, possibly in part through the inhibition of monoamine oxidase (MAO). Anthocyanins and their aglycons, responsible for the typical color of berries, inhibit MAO isoforms A or B with IC50 values corresponding to the micromolar range. Other studies suggest that cocoa extracts, whose main components are procyanidins, attenuate depressive symptoms in rats. Resveratrol, one of the most important natural stilbenoid, inhibits noradrenaline and serotonin reuptake in rats, and significantly decreases anxiety/depressive behaviours while increasing hippocampal serotonin and noradrenaline levels. Trans-resveratrol possesses MAO-A inhibitory effects in different brain areas, particularly in the frontal cortex and hippocampus, as already reported for tea catechins. Although these effects have been documented in rodent models, further randomized controlled trials in this area are warranted. However, so far, there is only correlative evidence between certain nutrients, such as omega-3 polyunsaturated fatty acids and B vitamins, and depression in human population studies. Growing evidence suggests that consumption of these compounds may represent an alternative strategy to delay the onset and progression of depression, and depressive-like symptoms. However, further randomized and placebo-controlled trials are necessary to confirm the potential of these compounds as a possible remedy for this debilitating disorder.


Codon choice directs constitutive mRNA levels in trypanosomes.
Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs. Third, translation was necessary for the accelerated mRNA turnover resulting from codon choice. Thus, in trypanosomes, the information determining the levels of most mRNAs resides in the open reading frame and translation is required to access this information.


A short self-report measure of problems with executive function suitable for administration via the Internet.
This article describes a short self-report measure of problems with executive function designed for use in Internet-mediated research. In Study 1, participants completed the online measure (Webexec) using a browser but under laboratory conditions. They also completed a paper self-report measure of executive problems (the Dysexecutive Questionnaire; DEX) and three objective tasks involving executive function: reverse digit span, semantic fluency (unconstrained), and semantic fluency (constrained). Webexec scores correlated positively with the DEX and negatively with the three executive tasks. Further evidence of construct validity came from Study 2, in which Webexec scores correlated positively with both use of cannabis and prospective memory problems reported in an online drug questionnaire. Webexec thus appears suitable for online research with normal populations.


Epidemiology and clinical significance of cervical erosion in women attending a family planning clinic.
Women attending a family planning clinic were studied to determine the relation between cervical erosion and clinical and social characteristics. The appearance of the cervix was recorded without knowledge of the women's symptoms. The prevalence of erosion increased with parity but, when the effects of other factors were controlled, decreased in women aged 35 and over. Erosion was significantly more common in women taking the "pill" and less common in women using barrier methods of contraception than in others. There was considerable variation between doctors in the reporting of erosion. No association was found between erosion and postcoital bleeding, dyspareunia, backache, or dysuria. There was a significant but modest association between erosion and vaginal discharge and a suggestion that erosion may sometimes be associated with nocturia and frequency of micturition. Vaginal flora was similar in women with and without erosion. Cervical erosion should not be regarded as pathological in asymptomatic women, nor should it be assumed necessarily to be the cause of symptoms in women with genitourinary complaints.


Ovine rotaviruses.
Rotavirus has been recognized as a predominant cause of acute diarrhea in young animals and humans. Rotavirus has segmented genome composed of 11 segments of double stranded RNA. The virus has a triple layered protein shell consisting of a core, an inner capsid and an outer capsid. The inner capsid protein is responsible for group specificity and based on it rotaviruses are classified into seven groups. Ovine rotavirus strains have only been identified into two serogroups (A and B). The two outer capsid proteins (VP7 and VP4) are responsible for G and P typing of rotavirus, respectively. Although rotavirus has been frequently reported in many animal species, data regarding ovine rotavirus strains is very scanty and limited. Only a few ovine rotaviruses have been isolated and characterized so far. Recently, the G and P types circulating in ovines have been identified. The ovine rotavirus strain NT isolated from a diarrheic lamb in China is being considered as a promising vaccine candidate for human infants.


Evidence for the role of organics in aerosol particle formation under atmospheric conditions.
New particle formation in the atmosphere is an important parameter in governing the radiative forcing of atmospheric aerosols. However, detailed nucleation mechanisms remain ambiguous, as laboratory data have so far not been successful in explaining atmospheric nucleation. We investigated the formation of new particles in a smog chamber simulating the photochemical formation of H(2)SO(4) and organic condensable species. Nucleation occurs at H(2)SO(4) concentrations similar to those found in the ambient atmosphere during nucleation events. The measured particle formation rates are proportional to the product of the concentrations of H(2)SO(4) and an organic molecule. This suggests that only one H(2)SO(4) molecule and one organic molecule are involved in the rate-limiting step of the observed nucleation process. Parameterizing this process in a global aerosol model results in substantially better agreement with ambient observations compared to control runs.


Standard of knowledge about their disease among patients with diabetes in Karachi, Pakistan.
The aim of this study was to determine the standard of knowledge among people with diabetes. Two hundred and thirty patients were randomly chosen from outpatient clinics and a 34-item multiple choice questionnaire administered to them. The questionnaire was structured to assess knowledge about the disease state, diagnostic tests, complications and management. The average score of correct answers for the group was 40%. A significantly higher score correlated with younger age (16-30 years), educational status and regular follow-up with a diabetic clinic. There was no significant difference in the knowledge score between males and females or between those on oral hypoglycemic agents (OHA) and insulin. Fifty percent of the patients could correctly answers questions regarding food and nutrition and only 60% were aware of target blood glucose levels for optimal control. It was alarming to learn that 75% of those on insulin did not know that using U-40 or U-100 insulin does not change the dose required. The study emphasizes the need for diabetes education at all levels, both for the patients as well as the health care providers to counter the pandemic of diabetes-related complications globally.


Prevalence and Impact of Pharmacy Students as Patient Care Extenders in Medically Underserved Community Pharmacies.
The objective of this study is to evaluate the prevalence and describe the patient care impact of student pharmacists completing community pharmacy rotations in medically underserved areas (MUAs) in Nebraska. A list of pharmacy student advanced pharmacy practice experience placements over a 3-year period were obtained from 2 pharmacy schools in Nebraska and then mapped in relation to MUAs in the state. A mixed-methods approach was used to compare and relate findings of a student-logged patient care activity database and semistructured interviews with pharmacy preceptors of participating students. Pharmacy students were placed in 21 (13%) of 159 identified pharmacies located in MUAs. Pharmacy preceptors felt students improved the quality of patient care provided as a result of more uninterrupted time with the patient. Preceptors also indicated that student presence assists both the student and the practicing pharmacist engage in more patient care services. There exists a significant opportunity to utilize advanced pharmacy practice students to extend patient care services and address health-care needs in underserved communities, but student placement in MUAs should be optimized.


SURVIVAL OF MICROORGANISMS IN A SIMULATED MARTIAN ENVIRONMENT. I. BACILLUS SUBTILIS VAR. GLOBIGII.
Survival of Bacillus subtilis var. globigii in a simulated Martian environment was demonstrated. Previous contact with the simulated Martian soil or atmosphere reduced germination or outgrowth of unheated spores, or both. Inoculation into simulated Martian soil and then flushing with a simulated Martian atmosphere were lethal to both vegetative cells and spores. After one diurnal temperature cycle (26 to -60 C), the majority of of cells present were spores. No further effect of the diurnal cycle on survival was noted in any of the experimental samples.


A cost/benefit analysis of clinical trial designs for COVID-19 vaccine candidates.
We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional and adaptive randomized clinical trials and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 756 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits-averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design-if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.


Differences in silencing of mismatched targets by sliced versus diced siRNAs.
It has been reported that the two major types of RNA interference triggers, the classical Dicer-generated small RNAs (siRNAs), which function with all members of the Argonaute (Ago) protein family in mammals, and the Ago2-sliced small RNAs (sli-siRNAs), which function solely through Ago2, have similar potency in target cleavage and repression. Here, we show that sli-siRNAs are generally more potent than siRNAs in silencing mismatched targets. This phenomenon is usually more apparent in targets that have mismatched nucleotides in the 3' supplementary region than in targets with mismatches in the seed region. We demonstrate that Ago2 slicer activity is a major factor contributing to the greater silencing efficiency of sli-siRNA against mismatched targets and that participation of non-slicing Agos in silencing mismatched siRNA targets may dilute the slicing ability of Ago2. The difference in length of the mature guide RNA used in sli-RISCs and si-RISCs may also contribute to the observed difference in knockdown efficiency. Our data suggest that a sli-siRNA guide strand is likely to have substantially stronger off-target effects than a guide strand with the same sequence in a classical siRNA and that Dicer and non-slicing Agos may play pivotal roles in controlling siRNA target specificity.


Replicated evolutionary divergence in the cuticular hydrocarbon profile of male crickets associated with the loss of song in the Hawaiian archipelago.
Female choice based on male secondary sexual traits is well documented, although the extent to which this selection can drive an evolutionary divergence in male traits among populations is less clear. Male field crickets Teleogryllus oceanicus attract females using a calling song and once contacted switch to courtship song to persuade them to mate. These crickets also secrete onto their cuticle a cocktail of long-chained fatty acids or cuticular hydrocarbons (CHCs). Females choose among potential mates based on the structure of male acoustic signals and on the composition of male CHC profiles. Here, we utilize two naturally occurring mutations that have arisen independently on two Hawaiian islands and render the male silent to ask whether the evolutionary loss of acoustic signalling can drive an evolutionary divergence in the alternative signalling modality, male CHC profiles. QST -FST comparisons revealed strong patterns of CHC divergence among three populations of crickets on the islands of Hawaii, Oahu and Kauai. Contrasts between wild-type and flatwing males on the islands of Oahu and Kauai indicated that variation in male CHC profiles within populations is associated with the loss of acoustic signalling; flatwing males had a relatively low abundance of long-chained CHCs relative to the short-chained CHCs that females find attractive. Given their dual functions in desiccation resistance and sexual signalling, insect CHCs may be particularly important traits for reproductive isolation and ultimately speciation.


Novel germline mutation in the transmembrane domain of HER2 in familial lung adenocarcinomas.
We encountered a family of Japanese descent in which multiple members developed lung cancer. Using whole-exome sequencing, we identified a novel germline mutation in the transmembrane domain of the human epidermal growth factor receptor 2 (HER2) gene (G660D). A novel somatic mutation (V659E) was also detected in the transmembrane domain of HER2 in one of 253 sporadic lung adenocarcinomas. Because the transmembrane domain of HER2 is considered to be responsible for the dimerization and subsequent activation of the HER family and downstream signaling pathways, we performed functional analyses of these HER2 mutants. Mutant HER2 G660D and V659E proteins were more stable than wild-type protein. Both the G660D and V659E mutants activated Akt. In addition, they activated p38, which is thought to promote cell proliferation in lung adenocarcinoma. Our findings strongly suggest that mutations in the transmembrane domain of HER2 may be oncogenic, causing hereditary and sporadic lung adenocarcinomas.


Valence, loop formation and universality in self-assembling patchy particles.
Patchy particles have emerged as an attractive model to mimic phase separation and self-assembly of globular proteins solutions, colloidal patchy particles, and molecular fluids where directional interactions are operative. In our previous work, we extensively explored the coupling of directional and isotropic interactions on both the phase separation and self-assembly in a system of patchy particles with five spots. Here, we extend this work to consider different patch valences and isotropic interaction strengths with an emphasis on self-assembly. Although the location of self-assembly transition lines in the temperature-density plane depend on a number of parameters, we find universal behavior of cluster size that is dependent only on the probability of a spot being bound, the patch valence, and the density. Using these principles, we quantify both the mass distribution and the shape for all clusters, as well as clusters containing loops. Following the logical implications of these results, combined with a simplified version of a mean-field theory that incorporates Flory-Stockmayer theory, we find a universal curve for the temperature dependence of cluster mass and a universal curve for the fraction of clusters that contain loops. As the curves are dependent on the particle valence, such results provide a method for parameterizing patchy particle models using experimental data.


Boric Acid Assisted Reduction of Graphene Oxide: A Promising Material for Sodium-Ion Batteries.
Reduced graphene oxide, an intensively investigated material for Li-ion batteries, has shown mostly unsatisfactory performance in Na-ion batteries, since its d-spacing is believed to be too small for effective insertion/deinsertion of Na(+) ions. Herein, a facile method was developed to produce boron-functionalized reduced graphene oxide (BF-rGO), with an enlarged interlayer spacing and defect-rich structure, which effectively accommodates the sodiation/desodiation and provides more active sites. The Na/BF-rGO half cells exhibit unprecedented long cycling stability, with ∼89.4% capacity retained after 5000 cycles (0.002% capacity decay per cycle) at 1000 mA·g(-1) current density. High specific capacity (280 mAh·g(-1)) and great rate capability were also delivered in the Na/BF-rGO half cells.


Biaxially stretchable, integrated array of high performance microsupercapacitors.
We report on the fabrication of a biaxially stretchable array of high performance microsupercapacitors (MSCs) on a deformable substrate. The deformable substrate is designed to suppress local strain applied to active devices by locally implanting pieces of stiff polyethylene terephthalate (PET) films within the soft elastomer of Ecoflex. A strain suppressed region is formed on the top surface of the deformable substrate, below which PET films are implanted. Active devices placed within this region can be isolated from the strain. Analysis of strain distribution by finite element method confirms that the maximum strain applied to MSC in the strain suppressed region is smaller than 0.02%, while that on the Ecoflex film is larger than 250% under both uniaxial strain of 70% and biaxial strain of 50%. The all-solid-state planar MSCs, fabricated with layer-by-layer deposited multiwalled carbon nanotube electrodes and patterned ionogel electrolyte of poly(ethylene glycol) diacrylate and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide having high-potential windows, are dry-transferred onto the deformable substrate and electrically connected in series and parallel via embedded liquid metal interconnection and Ag nanowire contacts. Liquid metal interconnection, formed by injecting liquid metal into the microchannel embedded within the substrate, can endure severe strains and requires no additional encapsulation process. This formed MSC array exhibits high energy and power density of 25 mWh/cm(3) and 32 W/cm(3), and stable electrochemical performance up to 100% uniaxial and 50% biaxial stretching. The high output voltage of the MSC array is used to light micro-light-emitting diode (μ-LED) arrays, even under strain conditions. This work demonstrates the potential application of our stretchable MSC arrays to wearable and bioimplantable electronics with a self-powered system.


Gene orders in the upstream of 16S rRNA genes divide genera of the family Halobacteriaceae into two groups.
In many prokaryotic species, 16S rRNA genes are present in multiple copies, and their sequences in general do not differ significantly owing to concerted evolution. At the time of writing, the genus Haloarcula of the family Halobacteriaceae comprises nine species with validly published names, all of which possess two to four highly heterogeneous 16S rRNA genes. Existence of multiple heterogeneous 16S rRNA genes makes it difficult to reconstruct a biological phylogenetic tree using their sequence data. If the orthologous gene is able to be discriminated from paralogous genes, a tree reconstructed from orthologous genes will reflect a simple biological phylogenetic relationship. At present, however, we have no means to distinguish the orthologous rRNA operon from paralogous ones in the members of the family Halobacteriaceae. In this study, we found that the dihydroorotate oxidase gene, pyrD, was present in the immediate upstream of one 16S rRNA gene in each of ten strains of the family Halobacteriaceae whose genome sequences have been determined, and the direction of the pyrD gene was opposite to that of the 16S rRNA genes. In two other strains whose genome sequences have been determined, the pyrD gene was present in far separated positions. We designed PCR primer sets to amplify DNA fragments encompassing a region from the conserved region of the pyrD gene to a conserved region of the tRNA-Ala gene or the 23S rRNA gene to determine the 16S rRNA gene sequences preceded by the pyrD gene, and to see if the pyrD gene is conserved in the immediate upstream of rRNA operon(s) in the type strains of the type species of 28 genera of the family Halobacteriaceae. Seventeen type strains, including the ten strains mentioned above, gave amplified DNA fragments of approximately 4000 bp, while eleven type strains, including the two strains mentioned above, did not give any PCR products. These eleven strains are members of the Clade I haloarchaea, originally defined by Walsh et al. (2004) and expanded by Minegishi et al. (2010). Analysis of contig sequences of three strains belonging to the Clade I haloarchaea also revealed the absence of the pyrD gene in the immediate upstream of any 16S rRNA genes. It may be scientifically sound to hypothesize that during the evolution of members of the family Halobacteriaceae, a pyrD gene transposition event happened in one group and this was followed by subsequent speciation processes in each group, yielding species/genera of the Clade I group and 'the rest' of the present family Halobacteriaceae.


Cat-scratch Disease.
Cat-scratch disease is a common infection that usually presents as tender lymphadenopathy. It should be included in the differential diagnosis of fever of unknown origin and any lymphadenopathy syndrome. Asymptomatic, bacteremic cats with Bartonella henselae in their saliva serve as vectors by biting and clawing the skin. Cat fleas are responsible for horizontal transmission of the disease from cat to cat, and on occasion, arthropod vectors (fleas or ticks) may transmit the disease to humans. Cat-scratch disease is commonly diagnosed in children, but adults can present with it as well. The causative microorganism, B. henselae, is difficult to culture. Diagnosis is most often arrived at by obtaining a history of exposure to cats and a serologic test with high titers (greater than 1:256) of immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, azithromycin has been shown in one small study to speed recovery. Infrequently, cat-scratch disease may present in a more disseminated form with hepatosplenomegaly or meningoencephalitis, or with bacillary angiomatosis in patients with AIDS.


Clinical manifestations of optic pit maculopathy as demonstrated by spectral domain optical coherence tomography.
The purpose of this retrospective study was to evaluate the characteristic features, including spectral-domain optical coherence tomography (SD-OCT), clinical course, and outcome of treatment if given for patients with optic disc pit maculopathy. We investigated a consecutive series of patients with a diagnosis of optic pit maculopathy treated between 2001 and 2012 at the Bascom Palmer Eye Institute. Patients were divided into two main groups, ie, patients who were observed without surgery and patients who received surgical intervention. The main outcome measures were presenting and final visual acuity, and changes in SD-OCT imaging were recorded. Other data including age, gender, eye, age of onset, length of follow-up, location of optic pit, and location of fluid by OCT were also recorded. On OCT, 67% (12/18) of the eyes showed schisis-like cavities, 22% (4/18) had only subretinal fluid, and 17% (3/18) had only a schisis-like cavity without subretinal fluid. In the patients managed by observation, visual acuity was ≥20/200 in 6/8 eyes initially and 6/8 eyes at last follow-up. Ten of 18 patients received either focal laser, surgery or both. Six of 10 eyes undergoing surgery had initial visual acuity ≥ 20/200, and 8 of 10 eyes undergoing surgery had a visual acuity of ≥20/200 at last follow-up. In this study, many eyes were observed and remained stable during follow-up. In eyes with reduced vision, surgical intervention produced variable outcomes, and persistent intraretinal/subretinal fluid was a common occurrence.


Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease.
In the recent years, a variety of bronchoscopic lung volume reduction (BLVR) procedures have emerged that may provide a treatment option to participants suffering from moderate to severe chronic obstructive pulmonary disease (COPD). To assess the effects of BLVR on the short- and long-term health outcomes in participants with moderate to severe COPD and determine the effectiveness and cost-effectiveness of each individual technique. Studies were identified from the Cochrane Airways Group Specialised Register (CAGR) and by handsearching of respiratory journals and meeting abstracts. All searches are current until 07 December 2016. We included randomized controlled trials (RCTs). We included studies reported as full text, those published as abstract only and unpublished data, if available. Two independent review authors assessed studies for inclusion and extracted data. Where possible, data from more than one study were combined in a meta-analysis using RevMan 5 software. AeriSealOne RCT of 95 participants found that AeriSeal compared to control led to a significant median improvement in forced expiratory volume in one second (FEV1) (18.9%, interquartile range (IQR) -0.7% to 41.9% versus 1.3%, IQR -8.2% to 12.9%), and higher quality of life, as measured by the St Georges Respiratory Questionnaire (SGRQ) (-12 units, IQR -22 units to -5 units, versus -3 units, IQR -5 units to 1 units), P = 0.043 and P = 0.0072 respectively. Although there was no significant difference in mortality (Odds Ratio (OR) 2.90, 95% CI 0.14 to 62.15), adverse events were more common for participants treated with AeriSeal (OR 3.71, 95% CI 1.34 to 10.24). The quality of evidence found in this prematurely terminated study was rated low to moderate. Airway bypass stentsTreatment with airway bypass stents compared to control did not lead to significant between-group changes in FEV1 (0.95%, 95% CI -0.16% to 2.06%) or SGRQ scores (-2.00 units, 95% CI -5.58 units to 1.58 units), as found by one study comprising 315 participants. There was no significant difference in mortality (OR 0.76, 95% CI 0.21 to 2.77), nor were there significant differences in adverse events (OR 1.33, 95% CI 0.65 to 2.73) between the two groups. The quality of evidence was rated moderate to high. Endobronchial coilsThree studies comprising 461 participants showed that treatment with endobronchial coils compared to control led to a significant between-group mean difference in FEV1 (10.88%, 95% CI 5.20% to 16.55%) and SGRQ (-9.14 units, 95% CI -11.59 units to -6.70 units). There were no significant differences in mortality (OR 1.49, 95% CI 0.67 to 3.29), but adverse events were significantly more common for participants treated with coils (OR 2.14, 95% CI 1.41 to 3.23). The quality of evidence ranged from low to high. Endobronchial valvesFive studies comprising 703 participants found that endobronchial valves versus control led to significant improvements in FEV1 (standardized mean difference (SMD) 0.48, 95% CI 0.32 to 0.64) and scores on the SGRQ (-7.29 units, 95% CI -11.12 units to -3.45 units). There were no significant differences in mortality between the two groups (OR 1.07, 95% CI 0.47 to 2.43) but adverse events were more common in the endobronchial valve group (OR 5.85, 95% CI 2.16 to 15.84). Participant selection plays an important role as absence of collateral ventilation was associated with superior clinically significant improvements in health outcomes. The quality of evidence ranged from low to high. Intrabronchial valvesIn the comparison of partial bilateral placement of intrabronchial valves to control, one trial favoured control in FEV1 (-2.11% versus 0.04%, P = 0.001) and one trial found no difference between the groups (0.9 L versus 0.87 L, P = 0.065). There were no significant differences in SGRQ scores (MD 2.64 units, 95% CI -0.28 units to 5.56 units) or mortality rates (OR 4.95, 95% CI 0.85 to 28.94), but adverse events were more frequent (OR 3.41, 95% CI 1.48 to 7.84) in participants treated with intrabronchial valves. The lack of functional benefits may be explained by the procedural strategy used, as another study (22 participants) compared unilateral versus partial bilateral placement, finding significant improvements in FEV1 and SGRQ when using the unilateral approach. The quality of evidence ranged between moderate to high. Vapour ablationOne study of 69 participants found significant mean between-group differences in FEV1 (14.70%, 95% CI 7.98% to 21.42%) and SGRQ (-9.70 units, 95% CI -15.62 units to -3.78 units), favouring vapour ablation over control. There was no significant between-group difference in mortality (OR 2.82, 95% CI 0.13 to 61.06), but vapour ablation led to significantly more adverse events (OR 3.86, 95% CI 1.00 to 14.97). The quality of evidence ranged from low to moderate. Results for selected BLVR procedures indicate they can provide significant and clinically meaningful short-term (up to one year) improvements in health outcomes, but this was at the expense of increased adverse events. The currently available evidence is not sufficient to assess the effect of BLVR procedures on mortality. These findings are limited by the lack of long-term follow-up data, limited availability of cost-effectiveness data, significant heterogeneity in results, presence of skew and high CIs, and the open-label character of a number of the studies.


Demographic risk factors for adverse birth outcomes in Puerto Rico in the PROTECT cohort.
Preterm birth is a major public health problem, especially in Puerto Rico where the rates are among the highest observed worldwide, reaching 18% in 2011. The Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) study is an ongoing investigation of environmental factors that contribute to this condition. In the present analysis, we sought to examine common risk factors for preterm birth and other adverse birth outcomes which have not been characterized previously in this unique population. Pregnant women from the PROTECT cohort are recruited from the heavily contaminated Northern coast of the island of Puerto Rico and are free of pre-existing conditions like diabetes. We examined associations between basic demographic, behavioral (e.g., tobacco and alcohol use), and pregnancy (e.g., season and year of delivery) characteristics as well as municipality of residence in relation to preterm birth (<37 weeks gestation), postterm birth (≥41 weeks gestation), and small and large for gestational age in univariate and multivariate logistic regression models. Between 2011 and 2017, 1028 live singleton births were delivered as part of the PROTECT cohort. Of these, 107 (10%) were preterm. Preterm birth rates were higher among women with low socioeconomic status, as indicated by education level and income, and among women with high pre-pregnancy body mass index (BMI). Odds ratios of small for gestational age delivery were higher for women who reported tobacco use in pregnancy and lower for women who delivered in the hurricane and dengue season (July-October). Overall, in pregnant women residing in Puerto Rico, socioeconomic status was associated with preterm birth but few other factors were associated with this or other adverse outcomes of pregnancy. Research to understand environmental factors that could be contributing to the preterm birth epidemic in Puerto Rico is necessary.


Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.


NTP Toxicity Study Report on the atmospheric characterization, particle size, chemical composition, and workplace exposure assessment of cellulose insulation (CELLULOSEINS).
Cellulose insulation (CI) is a type of thermal insulation produced primarily from recycled newspapers. The newspapers are shredded, milled, and treated with fire-retardant chemicals. The blowing process for installing CI generates a significant quantity of airborne material that presents a potential inhalation hazard to workers. CI was selected for study based upon the high production volume, the potential for widespread human exposure, and a lack of toxicity data; insufficient information was available to determine whether inhalation studies in laboratory animals were technically feasible or necessary. Studies were conducted to characterize the chemical and physical properties of CI aerosols, to evaluate the potential acute pulmonary toxicity of CI, and to assess occupational exposure of CI installers. Workplace exposure assessments were conducted in collaboration with the National Institute for Occupational Safety and Health (NIOSH, 2001). Chemical analyses were performed on samples of bulk CI from four major United States manufacturers. All samples of the bulk CI were found to contain primarily amorphous cellulose (60% to 65%) with a smaller crystalline component (35% to 40%). The crystalline phase was primarily native cellulose (75% to 85%) with a minor amount of cellulose nitrate (15% to 25%). Elemental analyses of acid digests of CI materials indicated that the major components (>0.1% by weight) included aluminum, boron, calcium, sodium, and sulfur. An acid-insoluble residue present in all four materials (3% to 5% of original sample weight) was found to consist primarily of aluminum silicate hydroxide (kaolinite; approximately 85%) with minor amounts (<5% each) of magnesium silicate hydroxide (talc), potassium aluminum silicate hydroxide (muscovite), and titanium oxide (rutile). Solvent extracts of the bulk materials were analyzed for organic components by gas chromatography with flame ionization detection. Analyses revealed a mass of poorly resolved peaks. Because of the very low concentrations, further quantitative and qualitative analyses were not performed. An aerosol generation system was designed to separate CI particles based upon aerodynamic size and to simulate the process used during CI installation at work sites. Less than 0.1% of each of the CI samples was collected as the small respirable particle fraction. The mean equivalent diameter of respirable particles ranged from 0.6 to 0.7 mum. The numbers of fibers in the respirable fractions ranged from 9.7 x 103 to 1.4 x 106 fibers/g of CI. The respirable particle fractions did not contain cellulose material and consisted mainly of fire retardants and small quantities of clays. The respirable fraction from one CI sample was administered by intratracheal instillation to male Fischer 344 rats at doses of 0, 0.625, 1.25, 2.5, 5, or 10 mg/kg body weight; the bronchoalveolar lavage (BAL) fluid cellularity was evaluated 3 days later. Based upon the relatively mild severity of the inflammatory response, a dose of 5 mg/kg body weight was selected for use in a subsequent 28-day study. Rats received CI, titanium dioxide (particle controls), or sterile saline (controls). BAL fluid was evaluated 1, 3, 7, 14, and 28 days after instillation, and lung histopathology was evaluated 14 and 28 days after treatment. CI caused a greater influx of inflammatory cells than titanium dioxide and caused significant increases in BAL fluid protein and lactate dehydrogenase. These CI-induced changes in BAL fluid parameters were transient and by day 14 were not significantly different than those observed in rats treated with titanium dioxide or phosphate-buffered saline. Unlike titanium dioxide, CI treatment caused a minimal to mild nonprogressive, minimally fibrosing granulomatous pneumonitis characterized by nodular foci of macrophages and giant cells. These results indicated that few respirable particles or fibers are likely generated during the CI application and that the acute pulmonary toxicity is minimal. The CI exposure assessment was conducted with 10 contractors located across the United States. Air samples of total dust and respirable dust were collected for scanning electron microscopy (SEM) to characterize any fibers in the dust. Two SEM air samples for each day of CI activities were collected from the installer and hopper operator. Bulk CI samples were collected and analyzed for metal, boron, and sulfate content. Real-time and video exposure monitoring was conducted to further characterize the CI dust and workers' exposures. The exposure assessment also included a medical component. Investigators collected 175 personal breathing zone (PBZ) total dust, 106 area total dust, and 90 area respirable dust air samples during CI-related activities at the 10 contractor sites. Twenty-six employees' total dust 8-hour time-weighted averages (TWAs) exceeded the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 15 mg/m3, and 42 exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) threshold-limit value (TLV) of 10 mg/m3. Respirable dust air sampling and real-time monitoring with particle size discrimination indicated low levels of respirable dust generation. The SEM analyses revealed that fibers were an average 28 mum in length and ranged from 5 mum to 150 mum. CI installers' PBZ total dust, area total dust, and area respirable dust air samples were all significantly higher during dry attic applications than wet attic applications (P<0.01). Conversely, the hopper operators' total dust exposures were significantly higher during wet wall and ceiling applications than dry wall and ceiling applications (P=0.02). Analyses of variance tests revealed that exposure concentrations in total dust air samples collected in the PBZ of all CI workers, including installers working in attics, installers during wall applications, hopper operators during attic applications, and hopper operators during wall and ceiling applications, varied significantly during dry applications (P<0.01). The respirable dust air samples collected in attic areas, hopper areas during attic applications, and hopper areas during wall and ceiling applications also differed significantly during dry applications (P=0.03). Twenty-three workers participated in the medical phase of the investigation. The workers completed medical and work history questionnaires, performed serial peak flow tests, and completed multiple acute symptom surveys. The medical questionnaires indicated respiratory, nasal, and skin symptoms that employees attributed to CI exposure. The most common symptoms reported while working with CI included nasal symptoms (35%), eye symptoms (35%), and morning phlegm production (25%). There was a temporal association between CI exposure and eye symptoms, but there was little evidence of lower respiratory system health conditions associated with CI exposure. Chemical analyses of the four bulk CI samples revealed only minor differences in additives. The major elemental components detected were aluminum, boron, calcium, sodium, and sulfur, but they were attributed to the fire retardants aluminum sulfate, boric acid, and sodium sulfate. For all four CI samples, less than 0.1% by weight was collected as the small respirable particle fraction. The fractions consisted mainly of fire retardants and smaller quantities of clays and did not contain cellulose material. Intratracheal instillation of the respirable fraction in rats produced minimal to mild inflammatory responses in the lungs with no increase in severity by 28 days after dosage. Although a significant increase in lung collagen was detected at day 28 in treated rats, microscopic evaluation revealed only a minimal to mild increase in collagen fibrils associated with granulomatous nodules. The results of these studies indicated that few respirable particles or fibers are generated during the aerosolization of CI, and that even at very high doses of respirable CI particles, acute pulmonary toxicity is minimal. These results are supported by the NIOSH workplace exposure assessment conducted on CI workers. Based on the air sample data collected from the 10 contractor site visits, there is a potential for overexposure to CI; however, respirable dust concentrations were typically low. There was increased potential for 8-hour TWAs exceeding the OSHA PEL for total and respirable dust when employees were involved in CI application activities for longer periods of time. There was evidence of work-related eye and mucous membrane irritation among some workers, which were possibly caused by the additives present in CI, such as boric acid. There was little evidence of lower respiratory system health conditions associated with CI exposure. Based upon the results of the CI chemical characterization studies, the pulmonary toxicity study, and the worksite exposure assessment, the NTP concluded that additional studies of CI in laboratory animals are not warranted at this time. However, the animal pulmonary toxicity studies and worker health surveys focused on acute CI exposures and do not preclude the possibility of toxicity resulting from chronic exposure. Although exposure concentrations of respirable CI particulate matter were low, additional information is needed on the biodurability and reactivity of CI particles and fibers in the respiratory tract. CI should continue to be regarded as a nuisance dust, and workers should continue to wear protective masks to prevent inhalation exposure to CI dusts.


microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
We performed an integrated analysis to identify microRNAs (miRNAs) and messenger RNAs (mRNAs) with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues. We analyzed miRNA and mRNA expression profiles of liver tissues from mice with diethylnitrosamine-induced hepatocarcinogenesis, conditional expression of lymphotoxin alpha and lymphotoxin beta, or inducible expression of a Myc transgene (Tet-O-Myc mice), as well as male C57BL/6 mice (controls). miRNA mimics were expressed and miRNAs and mRNAs were knocked down in human (Huh7, Hep3B, JHH2) hepatoma cell lines; cells were analyzed for viability, proliferation, apoptosis, migration, and invasion. Cells were grown as xenograft tumors in nude mice and analyzed. We combined in silico target gene prediction with mRNA profiles from all 3 mouse models. We quantified miRNA levels in 146 fresh-frozen tissues from patients (125 HCCs, 17 matched nontumor tissues, and 4 liver samples from patients without cancer) and published human data sets and tested correlations with patient survival times using Kaplan-Meier curves and the log-rank test. Levels of NUSAP1 mRNA were quantified in 237 HCCs and 5 nontumor liver samples using the TaqMan assay. Levels of the miRNA 193a-5p (MIR193A-5p) were reduced in liver tumors from all 3 mouse tumor models and in human HCC samples, compared with nontumor liver tissues. Expression of a MIR193A-5p mimic in hepatoma cells reduced proliferation, survival, migration, and invasion and their growth as xenograft tumors in nude mice. We found nucleolar and spindle-associated protein 1 (NUSAP1) to be a target of MIR193A-5p; HCC cells and tissues with low levels of MIR193A-5p had increased expression of NUSAP1. Increased levels of NUSAP1 in HCC samples correlated with shorter survival times of patients. Knockdown of NUSAP1 in Huh7 cells reduced proliferation, survival, migration, and growth as xenograft tumors in nude mice. Hydrodynamic tail-vein injections of a small hairpin RNA against NUSAP1 reduced growth of Akt1-Myc-induced tumors in mice. MIR193A-5p appears to prevent liver tumorigenesis by reducing levels of NUSAP1. Levels of MIR193A-5p are reduced in mouse and human HCC cells and tissues, leading to increased levels of NUSAP1, associated with shorter survival times of patients. Integrated analyses of miRNAs and mRNAs in tumors from mouse models can lead to identification of therapeutic targets in humans. The currently reported miRNA and mRNA profiling data have been submitted to the Gene Expression Omnibus (super-series accession number GSE102418).


The multiparty coherent channel and its implementation with linear optics.
The continuous-variable coherent (conat) channel is a useful resource for coherent communication, supporting coherent teleportation and coherent superdense coding. We extend the conat channel to multiparty conditions by proposing definitions on multiparty position-quadrature and momentum-quadrature conat channel. We additionally provide two methods to implement this channel using linear optics. One method is the multiparty version of coherent communication assisted by entanglement and classical communication (CCAECC). The other is multiparty coherent superdense coding.


The provision of seven day multidisciplinary staffing in Scottish acute medical units: a cross-sectional study.
Acute medical units (AMUs) are a central component of the admission pathway for the majority of medical patients presenting to hospital in the United Kingdom and other international settings. Detail on multidisciplinary staffing provision on weekdays and weekends is lacking. Equity of staffing across 7 days is a strategic priority for national health services in the United Kingdom. To evaluate weekday compared with weekend multidisciplinary staffing in a national set of AMUs. Cross-sectional survey. Twenty-nine Scottish AMUs were identified and all were included in the study population. Data were collected by semi-structured interviews with nursing, pharmacy, therapy, non-consultant medical and consultant staff. Staffing was quantified in staff hours. A correction factor of 0.5 was applied to non-dedicated staff. The percentage of weekend/weekday staffing was calculated for each unit and the mean of these percentages was calculated to give a summary measure for each professional group. As a percentage of weekday staffing levels, weekend staffing across the units was 93.8% for nursing staff; 2.2% for pharmacy staff; 13.1% for therapy staff; 69.6% for non-consultant staff and 65.0% for consultant staff. There is a contrast between weekday and weekend staffing on the AMU, with reductions at weekends in total staff hours, the proportion of dedicated vs. undedicated staff and the seniority of nursing staff. The weekday/weekend difference was far more pronounced for allied healthcare professional staff than any other group. These findings have potential implications for patient outcomes, quality of care, hospital flow and workforce planning.


Access and cost barriers to mental health care, by insurance status, 1999-2010.
The cost of mental health services has always been a great barrier to accessing care for people with mental health problems. This article documents changes in insurance coverage and cost for mental health services for people with public insurance, private insurance, and no coverage. In 2009-10 people with mental health problems were more likely to have public insurance and less likely to have private insurance than in 1999-2000. Although access to specialty care remained relatively stable for people with mental illnesses, cost barriers to care increased among the uninsured and the privately insured who had serious mental illnesses. The rise in cost barriers among those with private insurance suggests that the current financing of care in the private insurance market is insufficient to alleviate cost burdens and has implications for reforms under the Affordable Care Act. People with mental health problems who are newly eligible to purchase private insurance under the act might still encounter high cost barriers to accessing care.


Recovery of Salmonella from bermudagrass exposed to simulated wastewater.
Most confined swine (Sus scrofa) feeding operations in the southeastern United States hold manure in lagoons and apply effluent on bermudagrass [Cynodon dactylon (L.) Pers.] as fertilizer. Salmonella enterica subsp. enterica (ex Kauffman and Edwards) Le Minor and Popoff, has been reported in Mississippi lagoons, but levels and potential for contamination of bermudagrass were unknown. A laboratory method was developed to examine Salmonella contamination of bermudagrass and levels of Salmonella were determined in lagoons. The U.S. Environmental Protection Agency (EPA) worst case water was used to simulate effluent in exposing bermudagrass to Salmonella. Exposed leaves were washed and bacteria enumerated. Contamination of leaves exposed to 10(6) cfu mL(-1) varied from 0 to 10(4) cfu per leaf within and among eight bermudagrass cultivars and five Salmonella isolates. No differences (P < 0.05) occurred between cultivars (n = 20) or isolates (n = 10). Data fitted (R2 = 0.93) to a contamination equation (y = 5 x 10(-6)X6.623) described the relationship between levels (Log10 cfu mL(-1)) of exposure (x) and contamination (y). In fall 2007 Salmonella levels from six lagoons ranged from 1.9 to 2.8 log10 MPN 100 mL(-1) and were below the threshold for contamination predicted by the equation. These preliminary results must be tested with effluents in the field, but considered alongside work of others, which report lagoon Salmonella levels to be highest in fall, suggest that Salmonella levels in effluents from these lagoons may be too low to produce measurable contamination on bermudagrass.


Robotic mechanical localization of prostate cancer correlates with magnetic resonance imaging scans.
To evaluate the concordance of cancer location of the tissue mapping from a mechanical pressure transducer with magnetic resonance imaging (MRI) scans. A total of 60 indentations were performed on 5 prostate specimens obtained after radical prostatectomy utilizing a robotic indentation system. The mechanical elastic moduli of suspected malignant lesions were calculated and mapped, and their locations were compared with suspicious areas of malignancy on MRI scans. The concordance rate between the location mapping from the robotic indentation system and MRI scans results was 90.0% (54/60). The sensitivity and specificity of the robotic indentation system were 87.9% (29/33) and 92.6% (25/27), respectively. The positive predictive value and negative predictive value were 93.5% (29/31) and 93.1% (27/29), respectively. The locations of malignant lesions derived from our robotic indentation system correlated strongly with the locations of suspected areas of malignancy on MRI scans. Our robotic system may provide a more targeted biopsy of the prostate than conventional non-targeted systemic biopsy, possibly improving the diagnostic accuracy of prostatic biopsies for cancer.


Infantile Amnesia: A Critical Period of Learning to Learn and Remember.
Infantile amnesia, the inability of adults to recollect early episodic memories, is associated with the rapid forgetting that occurs in childhood. It has been suggested that infantile amnesia is due to the underdevelopment of the infant brain, which would preclude memory consolidation, or to deficits in memory retrieval. Although early memories are inaccessible to adults, early-life events, such as neglect or aversive experiences, can greatly impact adult behavior and may predispose individuals to various psychopathologies. It remains unclear how a brain that rapidly forgets, or is not yet able to form long-term memories, can exert such a long-lasting and important influence. Here, with a particular focus on the hippocampal memory system, we review the literature and discuss new evidence obtained in rats that illuminates the paradox of infantile amnesia. We propose that infantile amnesia reflects a developmental critical period during which the learning system is learning how to learn and remember.


Editor's Choice – Durability of Endovascular Repair in Blunt Traumatic Thoracic Aortic Injury: Long-Term Outcome from Four Tertiary Referral Centers.
To analyze the early and long-term survival and re-intervention rate in patients undergoing TEVAR for blunt traumatic thoracic aortic injury. This was a consecutive case series. Between the years 2001 and 2010, a total of 74 patients underwent TEVAR for blunt traumatic thoracic aortic injury at four tertiary referral centers, three in Sweden and one in Switzerland. The median age of the patients was 41 years, and 16% were women. Demographic, procedural, and outcome data were collected and reviewed retrospectively. The patients were followed up during 2013-2014. Early (30 day) mortality was 9% (7 patients), with only two cases directly related to the aortic injury; in hospital mortality was 14% as three patients died during the primary hospital admission within the first 6 months. Most patients had sustained severe injuries to other organ systems, and among all in hospital deaths brain injury was the predominant cause. Five year survival in the whole group was 81%. Re-intervention was needed in 16% (12 patients) during the first year, half of them within the first month. Only one patient underwent re-intervention more than 1 year after the initial procedure. Infolding and partial stentgraft collapse was the reason for the secondary procedure in five of the 13 patients; in three it occurred within 3 weeks of the acute TEVAR. TEVAR allows rapid and effective therapy in trauma patients with blunt aortic injury. The outcome is dependent on the severity of the concomitant injuries. The treatment is durable during the first decade after the procedure, but even longer follow up is needed to determine the impact of TEVAR in young patients on the degenerative changes that take place in the aging aorta.


Microwave-assisted solution-phase synthesis and DART-mass spectrometric monitoring of a combinatorial library of indolin-2,3-dione schiff bases with potential antimycobacterial activity.
A combinatorial library composed of eleven hydrazides A-K and eleven indolin-1,2-dione derivatives 1-11 has been designed to formally generate sublibraries of 22 mixtures, M(1)-M(22) comprising of 121 Schiff bases, A-K(1-11). The designed library has been synthesized by the solution-phase method and microwave-assisted synthetic techniques. The formation of individual compounds of each mixture was confirmed by Direct Analysis in Real Time (DART) as ionization technique connected to an Ion Trap as a mass detector. The synthesized mixtures were evaluated for their antimycobacterial activity against four Mycobacterium strains; M. intercellulari, M. xenopi, M. cheleneoi and M. smegmatis. Variable antimycobacterial activity was revealed with the investigated mixtures and maximum activity was shown by M(8), M(10), M(11), and M(15) with MIC values of 1.5, 3.1, 6.2 and 0.09 μg/mL, respectively. Application of the indexed method of analysis on these active mixtures revealed that compounds D(8), D(10) and D(11) may contribute to the activity of the tested mixtures.


Optimizing electronic standard cell libraries for variability tolerance through the nano-CMOS grid.
The project Meeting the Design Challenges of nano-CMOS Electronics (http://www.nanocmos.ac.uk) was funded by the Engineering and Physical Sciences Research Council to tackle the challenges facing the electronics industry caused by the decreasing scale of transistor devices, and the inherent variability that this exposes in devices and in the circuits and systems in which they are used. The project has developed a grid-based solution that supports the electronics design process, incorporating usage of large-scale high-performance computing (HPC) resources, data and metadata management and support for fine-grained security to protect commercially sensitive datasets. In this paper, we illustrate how the nano-CMOS (complementary metal oxide semiconductor) grid has been applied to optimize transistor dimensions within a standard cell library. The goal is to extract high-speed and low-power circuits which are more tolerant of the random fluctuations that will be prevalent in future technology nodes. Using statistically enhanced circuit simulation models based on three-dimensional atomistic device simulations, a genetic algorithm is presented that optimizes the device widths within a circuit using a multi-objective fitness function exploiting the nano-CMOS grid. The results show that the impact of threshold voltage variation can be reduced by optimizing transistor widths, and indicate that a similar method could be extended to the optimization of larger circuits.


Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant.
Contemporary auditory brainstem implant (ABI) performance is limited by reliance on electrical neurostimulation with its accompanying channel cross talk and current spread to non-auditory neurons. A new generation ABI based on optogenetic technology may ameliorate limitations fundamental to electrical stimulation. The most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively slow kinetic properties may prevent the encoding of auditory information at high stimulation rates. In the present study, we compare the temporal resolution of light-evoked responses of ChR2 to a recently developed fast opsin, Chronos, to ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral craniotomy was used to express Chronos or ChR2 in the cochlear nucleus (CN). Following a four to eight week incubation period, blue light (473 nm) was delivered via an optical fiber placed directly on the surface of the infected CN, and neural activity was recorded in the contralateral inferior colliculus (IC). Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high pulse rates. In addition, optical stimulation evoked excitatory responses throughout the tonotopic axis of the IC. Synchrony of the light-evoked response to stimulus rates of 14-448 pulses/s was higher in Chronos compared to ChR2 mice (p < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate that Chronos has the ability to drive the auditory system at higher stimulation rates than ChR2 and may be a more ideal opsin for manipulation of auditory pathways in future optogenetic-based neuroprostheses. This article is part of a Special Issue entitled "Lasker Award".


Biochemical Characterization of Mycobacterium tuberculosis DNA Repair Enzymes - Nfo, XthA and Nei2.
Tuberculosis (TB) is a human disease caused by Mycobacterium tuberculosis (Mtb). Treatment of TB requires long-term courses of multi-drug therapies to eliminate subpopulations of bacteria, which sometimes persist against antibiotics. Therefore, understanding of the mechanism of Mtb antibiotic-resistance is extremely important.During infection, Mtb overcomes a variety of body defense mechanisms, including treatment with the reactive species of oxygen and nitrogen. The bases in DNA molecule are susceptible to the damages caused by reactive forms of intermediate compounds of oxygen and nitrogen. Most of this damage is repaired by the base excision repair (BER) pathway. In this study, we aimed to biochemically characterize three Mtb DNA repair enzymes of BER pathway. XthA, nfo, and nei genes were identified in mycobacteria by homology search of genomic sequences available in the GenBank database. We used standard methods of genetic engineering to clone and sequence Mtb genes, which coded Nfo, XthA and Nei2 repair enzymes. The protein products of Mtb genes were expressed and purified in Escherichia coli using affinity tags. The enzymatic activity of purified Nfo, XthA, and Nei2 proteins were measured using radioactively labeled DNA substrates containing various modified residues. The genes end (Rv0670), xthA (Rv0427c), and nei (Rv3297) were PCR amplified using genomic DNA of Mtb H37Rv with primers that contain specific restriction sites. The amplified products were inserted into pET28c(+) expression vector in such a way that the recombinant proteins contain C-terminal histidine tags. The plasmid constructs were verified by sequencing and then transformed into the Escherichia coli BL21 (DE3) strain. Purification of recombinant proteins was performed using Ni2+ ions immobilized affinity column, coupled with the fast performance liquid chromatography machine AKTA. Identification of the isolated proteins was performed by protein mass spectrometry by ion trap tandem MS/MS on nLC-ESI-Ion-Trap platform. Biochemical characterization of DNA repair protein-catalyzed activity was carried out by measuring apurinic/apyrimidinic endonuclease, DNA glycosylase, exonuclease, and 3'-repair diesterase functions. In addition, effect of the opposite base and the influence of metal ion cofactors were measured. Results of the ongoing study will help us define the role of DNA repair enzymes in the emergence of mutations in the mycobacterial genome and, possibly, the origins of multi-drug resistance in mycobacteria.


Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA.
Genetic evidence indicates that Drosophila defense against Gram-positive bacteria is mediated by two putative pattern recognition receptors acting upstream of Toll, namely Gram-negative binding protein 1 (GNBP1) and peptidoglycan recognition protein SA (PGRP-SA). Until now however, the molecular recognition proceedings for sensing of Gram-positive pathogens were not known. In the present, we report the physical interaction between GNBP1 and PGRP-SA using recombinant proteins. GNBP1 was able to hydrolyze Gram-positive peptidoglycan (PG), while PGRP-SA bound highly purified PG fragments (muropeptides). Interaction between these proteins was enhanced in the presence of PG or muropeptides. PGRP-SA binding depended on the polymerization status of the muropeptides, pointing to constraints in the number of PGRP-SA molecules bound for signaling initiation. We propose a model whereby GNBP1 presents a processed form of PG for sensing by PGRP-SA and that a tripartite interaction between these proteins and PG is essential for downstream signaling.


Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability.
The exact function of the adult brain neurogenesis remains elusive, although it has been suggested to play a role in learning and memory processes. In our studies, we employed cyclin D2 gene knockout (cD2 KO) mice showing impaired neurogenesis as well as decreased hippocampal size. However, irrespectively of the genetic background of cD2 KO mice, this phenotype resulted in neither deficits in the hippocampal-dependent learning ability nor the memory formation. In the present study, cD2 KO mice and control littermates were subjected to hippocampal-dependent behavioral tests with little or no learning component. The knockout mice showed significant impairment in such species-typical behaviors as nest construction, digging, and marble burying. They were building none or poorer nests, digging less robustly, and burying fewer marbles than control mice. Such impairments were previously described, e.g., in animals with hippocampal lesions. Moreover, cD2 KO animals were also more active in the open field and automated motility chamber as well as showed increased explorative behavior in IntelliCage. Both increased motility and explorative behaviors were previously observed in hippocampally lesioned animals. Finally, cD2 KO mice showed normal sucrose preference, however starting from the second exposure to the sweetened solution, while control animals displayed a strong preference immediately. Presented results suggest that either morphological abnormalities of the hippocampal formation or adult brain neurogenesis impairment (or both) alter hippocampal-dependent behaviors of mutant mice without influencing learning abilities. These results may also suggest that adult brain neurogenesis is involved in species-typical behaviors.


Competing exchange interactions on the verge of a metal-insulator transition in the two-dimensional spiral magnet Sr3Fe2O7.
We report a neutron scattering study of the magnetic order and dynamics of the bilayer perovskite Sr(3)Fe(2)O(7), which exhibits a temperature-driven metal-insulator transition at 340 K. We show that the Fe(4+) moments adopt incommensurate spiral order below T(N) = 115 K and provide a comprehensive description of the corresponding spin-wave excitations. The observed magnetic order and excitation spectra can be well understood in terms of an effective spin Hamiltonian with interactions ranging up to third-nearest-neighbor pairs. The results indicate that the helical magnetism in Sr(3)Fe(2)O(7) results from competition between ferromagnetic double-exchange and antiferromagnetic superexchange interactions whose strengths become comparable near the metal-insulator transition. They thus confirm a decades-old theoretical prediction and provide a firm experimental basis for models of magnetic correlations in strongly correlated metals.


Past makes future: role of pFC in prediction.
The pFC enables the essential human capacities for predicting future events and preadapting to them. These capacities rest on both the structure and dynamics of the human pFC. Structurally, pFC, together with posterior association cortex, is at the highest hierarchical level of cortical organization, harboring neural networks that represent complex goal-directed actions. Dynamically, pFC is at the highest level of the perception-action cycle, the circular processing loop through the cortex that interfaces the organism with the environment in the pursuit of goals. In its predictive and preadaptive roles, pFC supports cognitive functions that are critical for the temporal organization of future behavior, including planning, attentional set, working memory, decision-making, and error monitoring. These functions have a common future perspective and are dynamically intertwined in goal-directed action. They all utilize the same neural infrastructure: a vast array of widely distributed, overlapping, and interactive cortical networks of personal memory and semantic knowledge, named cognits, which are formed by synaptic reinforcement in learning and memory acquisition. From this cortex-wide reservoir of memory and knowledge, pFC generates purposeful, goal-directed actions that are preadapted to predicted future events.


Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice.
To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.


Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis.
T helper (Th) 1-mediated immune responses are associated with adverse outcomes in a number of models of autoimmune disease. Previous work has focused on the role that cytokines secreted by Th1 cells play in mediating pathologic tissue injury. To evaluate other mechanisms by which Th1 cells may be specialized to coordinate the complex effector cell interactions of a destructive immune response, CD4+ T cells specific for influenza hemagglutinin (HA) were differentiated into Th1 or Th2 subsets and transferred into transgenic mice expressing HA under control of the beta myosin heavy chain promoter, which drives heart specific expression of HA. CD4+ T cells polarized to a Th1 phenotype mediated a more destructive myocarditis than Th2 cells. Strikingly, the Th1-mediated inflammation was comprised primarily of CD8+ T cells and macrophages, suggesting a specialized recruitment function for Th1 cells. Further studies revealed that Th1 and Th2 subsets had polarized secretion of certain CC-chemokines, including MIP-1alpha and RANTES, which have selective recruitment properties on effector cells. Th1 cell secreted factors were up to 1000-fold more potent in inducing CD8+ T cell migration compared to Th2 cell secreted factors, and this advantage was partially mediated by their specialized MIP-1alpha secretion. These findings indicate that Th subsets have distinct patterns of CC-chemokine secretion and this specialization by Th1 cells mediates the recruitment of cytotoxic effector cells into destructive inflammatory responses.


A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
Regulation of multipotent cardiac progenitor cell (CPC) expansion and subsequent differentiation into cardiomyocytes, smooth muscle or endothelial cells is a fundamental aspect of basic cardiovascular biology and cardiac regenerative medicine. However, the mechanisms governing these decisions remain unclear. Here, we show that Wnt/beta-catenin signalling, which promotes expansion of CPCs, is negatively regulated by Notch1-mediated control of phosphorylated beta-catenin accumulation within CPCs, and that Notch1 activity in CPCs is required for their differentiation. Notch1 positively, and beta-catenin negatively, regulated expression of the cardiac transcription factors, Isl1, Myocd and Smyd1. Surprisingly, disruption of Isl1, normally expressed transiently in CPCs before their differentiation, resulted in expansion of CPCs in vivo and in an embryonic stem (ES) cell system. Furthermore, Isl1 was required for CPC differentiation into cardiomyocyte and smooth muscle cells, but not endothelial cells. These findings reveal a regulatory network controlling CPC expansion and cell fate that involves unanticipated functions of beta-catenin, Notch1 and Isl1 that may be leveraged for regenerative approaches involving CPCs.


Localization of PS6K to chromosomal region 17q23 and determination of its amplification in breast cancer.
The application of comparative genomic hybridization to the analysis of genetic abnormalities in breast carcinoma has consistently revealed that chromosome region 17q22-24 is a frequent site of gene amplification in this type of cancer. As part of an examination of expressed sequence tags for novel amplified genes in this region, we identified PS6K amplifications in both breast tumor tissues and cell lines. PS6K was localized to 17q23 and encodes a serine-threonine kinase whose activation is thought to regulate a wide array of cellular processes involved in the mitogenic response including protein synthesis, translation of specific mRNA species, and cell cycle progression from G1 to S phase. Northern and Western analyses revealed that amplification of this gene was accompanied by corresponding increases in mRNA and protein expression, respectively. These data represent the first determination of a gene amplification within 17q22-24 in breast cancer and suggest an oncogenic activity for PS6K.


Ball milling pretreatment of corn stover for enhancing the efficiency of enzymatic hydrolysis.
Ethanol can be produced from lignocellulosic biomass with the usage of ball milling pretreatment followed by enzymatic hydrolysis and fermentation. The sugar yields from lignocellulosic feed stocks are critical parameters for ethanol production process. The research results from this paper indicated that the yields of glucose and xylose were improved by adding any of the following dilute chemical reagents: H(2)SO(4), HCl, HNO(3), CH(3)COOH, HCOOH, H(3)PO(4), and NaOH, KOH, Ca(OH)(2), NH(3)·H(2)O in the ball milling pretreatment of corn stover. The optimal enzymatic hydrolysis efficiencies were obtained under the conditions of ball milling in the alkali medium that was due to delignification. The data also demonstrated that ball milling pretreatment was a robust process. From the microscope image of ball milling-pretreated corn stover, it could be observed that the particle size of material was decreased and the fiber structure was more loosely organized. Meanwhile, the results indicate that the treatment effect of wet milling is better than that of dry milling. The optimum parameters for the milling process were ball speed of 350 r/min, solid/liquid ratio of 1:10, raw material particle size with 0.5 mm, and number of balls of 20 (steel ball, Φ = 10 mm), grinding for 30 min. In comparison with water milling process, alkaline milling treatment could increase the enzymatic hydrolysis efficiency of corn stover by 110%; and through the digestion process with the combination of xylanase and cellulase mixture, the hydrolysis efficiency could increase by 160%.


A unifying theory for the multifactorial origin of cerebellar tonsillar herniation and hydrocephalus in osteopetrosis.
Osteopetrosis is a rare congenital metabolic bone disease. There are very few reports in the literature associating cerebellar tonsillar herniation (CTH) and hydrocephalus requiring neurosurgical attention. The authors present cases of osteopetrosis requiring neurosurgical intervention from their practice and offer a detailed account of the literature. A retrospective review was conducted at the authors' institution, and all children with osteopetrosis requiring neurosurgical attention were identified. Medical charts and radiographic studies were reviewed. Data including age at presentation, sex, symptoms at presentation, age at follow-up, the presence of any neurological comorbidities, and surgical procedures performed were recorded. Four patients were identified as having osteopetrosis requiring neurosurgical attention at the authors' institution between January 1, 2005, and January 1, 2014. There were 3 females and 1 male with an average age at presentation of 11.1 years; patients were observed for a mean of 4.4 years. All of the patients were identified as harboring jugular foraminal stenosis and CTH. Seventy-five percent of these patients developed hydrocephalus, and in those cases a triventricular pattern of dilation was noted. One patient developed syringomyelia. Three of the 4 patients underwent neurosurgical procedures. Cerebrospinal fluid diversion was performed in 2 patients via a ventriculoperitoneal shunt in one case and an endoscopic third ventriculostomy (ETV) in the other. The former patient required a proximal revision at 2 years for bony overgrowth at the site of the bur hole. Two patients underwent a suboccipital decompression. In patients undergoing CSF diversion, there was improvement in ventricle size. Variable degrees of hindbrain crowding and/or CTH are mentioned throughout the literature, suggesting that this entity is nearly always present in this patient population. The progressive triventricular hydrocephalus seen in these cases results from a complex combination of both communicating and noncommunicating pathology, which may depend on the type of osteopetrosis, age at presentation, and the presence and degree of venous collateralization, and it appears that the hydrocephalus is more prevalent and more likely to be treated in infants and in the younger, school-aged population. The acquired hindbrain fullness in conjunction with the triventricular pattern of hydrocephalus has kept the authors enthusiastic regarding the use of ETV in these complicated cases.


Comparative analysis of tranexamic acid use in minimally invasive versus open craniosynostosis procedures.
Intraoperatively administered tranexamic acid (TXA) lessens blood loss during orthopedic and cardiovascular surgery. Its use for craniosynostosis surgery warrants investigation. Therefore, we analyzed our use of TXA during minimally invasive (MI) and open craniosynostosis procedures. Fifty-six patients were retrospectively studied: 20 in the MI group, 10 receiving TXA; 36 in the open group, 16 receiving TXA. Study variables were weight-adjusted estimated blood loss (EBL) and calculated blood loss (CBL), transfusion and incidence, transfusion volume, and complications. Calculated blood loss was determined by a novel formula based on red cell mass. In the MI group, median EBL was significantly lower for TXA recipients (9.62 vs 15.94 mL/kg, P = 0.0231), whereas median CBL was not (36.59 vs 34.12 mL/kg, P = 0.7976). Transfusion incidences were 80% TXA versus 100% control (P = 0.4737). Median transfusion volume trended lower (10.76 vs 19.43 mL/kg, P = 0.0723).In the open group, median EBL and CBL for TXA recipients were lower but not significantly different than for nonrecipients (21.86 vs 23.40 mL/kg, P = 0.7416; 53.54 vs 80.13; P = 0.3137). All patients had a transfusion. Median transfusion volume for TXA recipients versus nonrecipients was 34.01 versus 40.35 mL/kg (P = 0.3137). Tranexamic acid greatly minimized the range of EBL and CBL in both surgical groups. There was a significant correlation between the CBL and EBL (P < 0.0001). There were no adverse events. Intraoperative TXA administration is safe with modest benefit suggested, especially in the MI group. Calculated blood loss correlated well with EBL at lower blood loss volumes, implicating it as a potential measurement of true blood loss.


The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain.
Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.


Primary Care Informatics Response to Covid-19 Pandemic: Adaptation, Progress, and Lessons from Four Countries with High ICT Development.
Internationally, primary care practice had to transform in response to the COVID pandemic. Informatics issues included access, privacy, and security, as well as patient concerns of equity, safety, quality, and trust. This paper describes progress and lessons learned. IMIA Primary Care Informatics Working Group members from Australia, Canada, United Kingdom and United States developed a standardised template for collection of information. The template guided a rapid literature review. We also included experiential learning from primary care and public health perspectives. All countries responded rapidly. Common themes included rapid reductions then transformation to virtual visits, pausing of non-COVID related informatics projects, all against a background of non-standardized digital development and disparate territory or state regulations and guidance. Common barriers in these four and in less-resourced countries included disparities in internet access and availability including bandwidth limitations when internet access was available, initial lack of coding standards, and fears of primary care clinicians that patients were delaying care despite the availability of televisits. Primary care clinicians were able to respond to the COVID crisis through telehealth and electronic record enabled change. However, the lack of coordinated national strategies and regulation, assurance of financial viability, and working in silos remained limitations. The potential for primary care informatics to transform current practice was highlighted. More research is needed to confirm preliminary observations and trends noted.


Administrative prescription review procedures and use of atypical antipsychotic medications in the Department of Veterans Affairs.
Atypical antipsychotic medications vary in cost with limited evidence of differences in effectiveness. Administrative prescription review has been proposed as a way of encouraging use of less expensive medication when there is no specific clinical justification for using more expensive medication. This study examined data from a national GAO survey of 876 veterans affairs (VA) psychiatrists, and national administrative data on the proportion of veterans actually receiving atypical antipsychotic medications. The proportion of psychiatrists in each region reporting that they did not feel free to prescribe expensive drugs when indicated was negatively correlated with the proportion of patients who filled prescriptions for clozapine, the most expensive atypical. The proportion reporting review procedures for prescribing olanzapine was significantly and negatively correlated with the proportion of veterans actually receiving prescriptions for olanzapine and, positively associated with the proportion prescribed risperidone. Nondirective administrative review procedures in VA are significantly associated with actual prescribing patterns and may generate modest cost savings in the prescription of atypical antipsychotic medication.


Proinflammatory (CD14+CD16++) monocytes in type 2 diabetes mellitus patients with/without chronic periodontitis.
Until date, the proportion of nonclassic monocytes in type 2 diabetic mellitus patients with and without chronic periodontitis has not been evaluated based on glycemic control. The objective of this study was to compare the proportion of CD14+CD16++ monocytes in type 2 diabetic patients with and without chronic periodontitis. In this cross sectional study A total of sixty individuals with type 2 diabetes mellitus (n = 15/group) were recruited. Individuals were grouped based on glycosylated hemoglobin A (HbA 1c) values and the presence of chronic periodontitis; Group 1 (diabetes mellitus with good glycemic control), Group 2 (diabetes mellitus with poor glycemic control), Group 3 (diabetic mellitus with chronic periodontitis and good glycemic control), Group 4 (diabetic mellitus with chronic periodontitis and poor glycemic control). Fluorochrome-conjugated monoclonal antibodies against CD14, CD16, and human leukocyte antigen-antigen D related was used to analyze the proportion of nonclassic monocytes by flow cytometry. One-way ANOVA with Tukey's post-hoc test was used to assess the significant differences in monocyte subpopulations. The Pearson's correlation test was used to assess the relationship between hemoglobin A1c values and percentage of nonclassical monocytes. In both the above statistical tools, the value of P < 0.05 is considered as significant level. Group 4 had the highest percentage of CD14+CD16++ monocytes 14.67% + 4.70%, followed by Group 3-9.73% + 0.60%, Group 2-9.32% + 2.03% and Group 1-5.92% + 0.63% (P < 0.001). Further, a statistically significant positive correlation between HbA (1c) levels and the proportion of CD14+CD16++ monocytes was observed. In the present study, we observed type 2 diabetes mellitus patients with poor glycemic control and chronic periodontitis showed more than two-fold increase in the proportion of nonclassic monocytes compared to type 2 diabetes mellitus patients with good glycemic control.


Validity of the mood disorder questionnaire: a general population study.
This study tested the validity in the adult general population of the Mood Disorder Questionnaire, a screening instrument for bipolar I and II disorders. The Mood Disorder Questionnaire has been validated in a psychiatric outpatient study group. A total of 711 subjects (stratified by Mood Disorder Questionnaire score) were randomly selected from a group of 85,358 adult respondents in a nationwide epidemiological general population sample that was balanced for key demographic variables. Of these, 695 subjects received a telephone interview involving an abbreviated version of the Structured Clinical Interview for DSM-IV. A sensitivity of 0.281 and a specificity of 0.972 were obtained for the Mood Disorder Questionnaire. The Mood Disorder Questionnaire is a useful screening instrument for bipolar I and II disorders in the community. The operating characteristics of the Mood Disorder Questionnaire in the general population differ substantially from its characteristics in outpatient psychiatric settings.


Anthropogenic disturbance affects the structure of bacterial communities.
Patterns of taxa abundance distributions are the result of the combined effects of historical and biological processes and as such are central to ecology. It is accepted that a taxa abundance distribution for a given community of animals or plants following a perturbation will typically change in structure from one of high evenness to increasing dominance. Subsequently, such changes in evenness have been used as indicators of biological integrity and environmental assessment. Here, using replicated experimental treehole microcosms perturbed with different concentrations of the pollutant pentachlorophenol, we investigated whether changes in bacterial community structure would reflect the effects of anthropogenic stress in a similar manner to larger organisms. Community structure was visualized using rank-abundance plots fitted with linear regression models. The slopes of the regression models were used as a descriptive statistic of changes in evenness over time. Our findings showed that bacterial community structure reflected the impact and the recovery from an anthropogenic disturbance. In addition, the intensity of impact and the rate of recovery to pre-perturbation structure were dose-dependent. These properties of bacterial community structures may potentially provide a metric for environmental assessment and regulation.


A Rapid Review of Available Evidence to Inform Indicators for Routine Monitoring and Evaluation of Respectful Maternity Care.
Some opportunities to routinely capture and improve respectful maternity care (RMC) during facility-based childbirth include quality improvement (QI) initiatives, community-based monitoring efforts through community score cards (CSC), and performance-based financing (PBF) initiatives. But there is limited guidance on which types of RMC indicators are best suited for inclusion in these initiatives. We sought to provide practical evidence-based recommendations on indicators that may be used for routine measurement of RMC in programs. We used a rapid review approach, which included (1) reviewing existing documents and publications to extract RMC indicators and identify which have or can be used in facility-based QI, CSCs, and PBF schemes; (2) surveying RMC and maternal health experts to rank indicators, and (3) analyzing survey data to select the most recommended indicators. We identified 49 indicators spanning several domains of RMC and mistreatment including dignified/nondignified care, verbal and physical abuse, privacy/confidentiality, autonomy/loss of autonomy, supportive care/lack thereof, communication, stigma, discrimination, trust, facility environment/culture, responsiveness, and nonevidence-based care. Based on the analysis of the survey data, we recommend 33 indicators (between 2 and 6 indicators for each RMC domain) that may be suited for incorporation in both facility-based QI and CSC-related monitoring efforts. Integrating RMC indicators into QI and CSC initiatives, as well as in other maternal and neonatal health programs, could help improve RMC at the facility and community level. More research is needed into whether RMC can be integrated into PBF initiatives. Integration of RMC indicators into programs to improve quality of care and other health system outcomes will facilitate routine monitoring and accountability around experience of care. Measurement and improvement of women's experiences will increase maternal health service utilization and improve quality of care as a means of reducing maternal and neonatal morbidity and mortality.