Successful gelfoam angioembolisation in anastomotic pseudoaneurysm: A case report.
The use of angioembolisation in patients with lower gastrointestinal tract haemorrhage has become well established, especially in cases of diverticular bleeding, or in bleeding from arterio-venous malformations. Pseudoaneurysms are rare and the evaluation of selective gelfoam angioembolisation amongst patients with lower gastrointestinal tract bleeding secondary to this etiology has not been extensively studied. The friable nature of pseudoaneurysms may lead to a greater risk of rupture during an attempted angioembolisation procedure. We describe the successful treatment and outcome of a lady who initially presented with perforation of the colon at the rectosigmoid junction, for which she underwent resection and anastomosis. A few days later, she was noted to have persistent hematochezia, which was secondary to bleeding pseudoaneurysms at the rectosigmoid branches of the inferior mesenteric artery. She successfully underwent selective angioembolisation of these pseudoaneurysms with gelfoam. She did not suffer any complications from the procedure. Although there have been significant advances in the armamentarium associated with percutaneous interventional radiology procedures for hemostasis in gastrointestinal bleeding, the use of selective angioembolisation for bleeding pseudoaneurysms have not been readily adopted due to the friable nature of the wall of the pseudoaneurysm, and its risk for rupture. Our case report illustrates that angioembolisation in such cases is feasible, and should be a consideration especially when the risk of surgical intervention is high. Selective gelfoam angioembolisation should be considered in the management of patients with bleeding from the gastrointestinal tract secondary to pseudoaneurysms.


The effect on colon visualization during colonoscopy of the addition of simethicone to polyethylene glycol-electrolyte solution: a randomized single-blind study.
Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38%; P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations.


The effect of the heterogeneity variance estimator on some tests of treatment efficacy.
The effect of two noniterative heterogeneity variance estimators on two test procedures for the overall treatment effect using the log odds ratio as the outcome measure is investigated. Using simulated significance levels, it is shown that in addition to being sensitive to changes in the magnitude of the heterogeneity variance, the standard test procedure in meta-analysis (or multicenter clinical trials) is also sensitive to the heterogeneity variance estimator used and attains significance levels that are far from the prescribed level. A second test procedure by Hartung [Hartung, J. (1999). An alternative method for meta-analysis. Biometrical J. 41:901-916], is shown to exhibit good control of type I error probability regardless of changes in the magnitude of the heterogeneity variance and the heterogeneity variance estimator used.


Fungal Nomenclature at IMC10: Report of the Nomenclature Sessions.
Three Nomenclature Sessions were convened during the 10(th) International Mycological Congress (IMC10) in Bangkok on 3-8 August 2014. In addition a Questionnaire was given to all delegates. This Report reviews and summarizes the views expressed in the Sessions and in the responses to the Questionnaire. The issues covered related to aspects of: registration, protected names, forgotten names, pleomorphic fungi, lichenized fungi, typification, diagnoses, and governance. In addition, reports were received from working groups preparing lists of names to be proposed for protection, and controversial cases of competing names were discussed. The Congress was mandated to ratify decisions of the Nomenclature Committee for Fungi (NCF) on the appointment of repositories for the registration of new fungal names. After discussion in the Sessions on the decision of the NCF to appoint three such bodies, a Resolution to that effect was approved by the Congress. The Congress also adopted a Resolution asking that the opinions of mycologists on future directions for the nomenclature of fungi be taken into account in formulating changes in the rules for consideration at the International Botanical Congress in 2017.


Directionally selective mnemonic properties of neurons in the lateral dorsal nucleus of the thalamus of rats.
The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animal's head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep-layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2-3 min. After this time, the directional preference (but not specificity) appeared to "rotate" systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems.


[Human T-cell leukemia (lymphoma) virus (HTLV-I) antibodies in Danish patients with cutaneous T-cell lymphoma].
HTLV-I antibodies were found in 10 out of 68 patients with cutaneous T-cell lymphoma (14%). HTLV antibodies were found in the earliest pre-diagnostic stage [Mycosis fungoides I (MF I), histologically non-diagnostic] as well as in the later stages (MF-III), where tumour cells are histologically apparent and the skin lesions have progressed from the plaque stage to the tumour stage. Of 4 patients with lymphomatoid papulosis, only 1 had positive HTLV antibody sera. Sequential studies of 6 patients demonstrated that the presence of HTLV-I antibodies was independent of the clinical remission - relapse stages in these patients. The present results show that HTLV-I or a related virus is found in Denmark and probably more widely distributed than was previously thought.


Construction of a Highly Diverse mRNA Library for in vitro Selection of Monobodies.
Recently, we developed transcription/translation coupled with the association of puromycin linker (TRAP) display as a quick in vitro selection method to obtain antibody-like proteins. For the in vitro selection, it is important to prepare mRNA libraries among which the diversity is high. Here, we describe a method for the preparation of monobody mRNA libraries with greater than 1013 theoretical diversity. First, we synthesized two long single-stranded DNAs that corresponded to fragments of monobody DNA, with random codons in the BC and FG loops. These oligonucleotides were ligated by T4 DNA ligase with the support of guide oligonucleotides containing 3' ends that were protected by a modification. After amplifying the product DNAs by PCR, one end of each DNA fragment was digested with the type II restriction enzyme BsaI, and the resulting DNA fragments were ligated using T4 DNA ligase. After amplification of the DNA product, mRNAs were synthesized by T7 RNA polymerase. This method is simple and could be used for the preparation of mRNA libraries for various antibody-like proteins. Graphic abstract: Construction of a highly diverse mRNA library.


Biochemical and genetic characterization of Yra1p in budding yeast.
Yra1p and its vertebrate homologues bind to the mRNA export factor Mex67p/TAP and are thought to play a role in mRNA export in vivo. To further characterize Yra1p, we used immunoaffinity chromatography to purify endogenous Yra1p complexes. These experiments demonstrated that two importin beta homologues (Kap123p and Pse1p) and the poly A tail-binding proteins Pab1p and Nab2p associate with Yra1p. The other major proteins that associate with Yra1p include proteins involved in mRNA and rRNA processing and the Yra1p-related protein Yra2p. Additional biochemical and genetic experiments suggest a close functional relationship between Yra1p and Yra2p. We generated a temperature-sensitive allele of YRA1 and used it to demonstrate that cells which lack the function of both Yra1p and Yra2p are able to exit a G0 arrest and go through several rounds of cell division before arresting. We also identified high-copy suppressors of the yra1-2 temperature-sensitive growth defect. These include SUB2, a splicing factor important in mRNA export, ULP1, a nuclear cysteine protease localized to the nuclear pore and involved in Smt3p/SUMO processing, and YRA2. Taken together, these results suggest that Yra1p has roles in diverse RNA processing events in addition to a role in mRNA export.


EVALUATION OF PERIOPERATIVE HIGH-SENSITIVE CARDIAC TROPONIN I AS A PREDICTIVE BIOMARKER OF MAJOR ADVERSE CARDIOVASCULAR EVENTS AFTER NONCARDIAC SURGERY.
Various studies suggest that perioperative concentrations of high-sensitivity troponins are incremental and predictive factors of a major adverse cardiac event (MACE) and all-cause mortality. The objective of the study was to evaluate the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in the development of MACE and all-cause mortality, within 30-days and 1-year follow-up after noncardiac surgery. In this prospective cohort study, we included men ≥ 45 years and women ≥ 55 years with ≥ 2 cardiovascular risk factors and undergoing intermediate or high-risk noncardiac surgery. Demographic and clinical information was collected from clinical charts. We measured baseline hs-cTnI 24 h before surgery, and its post-operative concentration 24 h after surgery. In the entire sample, 8 patients (8.6%) developed MACE at 30-days follow-up (4 deaths), 12 (12.9%) within the 1st year (7 deaths), and 17 (18.2%) after complete post-surgical follow-up (10 deaths). We observed higher baseline and post-operative concentrations in patients who presented MACE (12 pg/ml vs. 3.5 pg/ml; p = 0.001 and 18.3 pg/ml vs. 5.45 pg/ml; p = 0.009, respectively). The hazard ratios (HRs) calculated by Cox regression analysis between the hs-cTnI baseline concentration and the post-operative development of MACE at 30-days and 1-year were 5.70 (95% confidence interval [CI], 1.10-29.40) with hs-cTnI > 6.2 pg/ml and 12.86 (95% CI, 1.42-116.34) with hs-cTnI > 3.3 pg/ml, respectively. The estimated post-operative HR death risk at 1-year was 14.43 (95% CI, 1.37-151.61) with hs-cTnI > 4.5 pg/ml. Pre-operative hs-cTnI was an independent predictive risk factor for MACE at 30-days and 1-year after noncardiac surgery and for all-cause mortality at 1-year after noncardiac surgery.


Cloning and nucleotide sequence of the Bacillus megaterium gene coding for small, acid-soluble spore protein B.
The Bacillus megaterium gene coding for small, acid-soluble spore protein (SASP) B was cloned and its nucleotide sequence was determined. The amino acid sequence predicted from the DNA sequence was identical to that determined previously for SASP B, with the exception of the amino-terminal methionine predicted from the gene sequence which is presumably removed posttranslationally and an asparagine residue predicted at position 21 which was originally identified as an aspartate residue. The mRNA encoded by the SASP B gene is synthesized for only a discrete period midway in sporulation, in parallel with mRNAs coding for other SASPs. The small size of the SASP B mRNA (365 nucleotides) indicated that the mRNA is monocistronic. The SASP B gene itself hybridized strongly to only one band in Southern blots of restriction enzyme digests of B. megaterium DNA, suggesting that the SASP B gene is not a member of a highly conserved multigene family, as is the case for other SASP genes.


The pan-cancer landscape of glutamate and glutamine metabolism: A comprehensive bioinformatic analysis across 32 solid cancer types.
Glutamine metabolism is a hallmark of cancer metabolism, which matters in the progression of the tumor. This synthetic study conducted a large-scale systematic analysis at the pan-cancer level on the glutamate and glutamine metabolism (GGM) across 32 solid tumors from the TCGA database. The glutamine metabolism activity was quantified through a scoring system. This study revealed that the GGM score in tumor tissues was up-regulated in 13 cancer types (BCLA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PAAD, PRAD, READ, STAD, THYM, UCEC) and down-regulated in 4 cancer types (CHOL, GBM, LIHC, THCA), exhibiting tissue specificity. The mRNA expression levels of glutamine metabolism-related genes were relatively high, and GLUL exhibited the highest expression level. The expression levels were up-regulated with copy number amplification. ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in protein levels in cancer tissues compared to normal tissues, making them potential pan-cancer therapeutic targets. For the TME related to glutamine metabolism, the GGM score exhibited significant immune and stromal environment inhibitory effects in all involved tumors. Up-regulated GGM score indicated the widespread promotion of drug resistance at the pan-cancer level. GGM score and glutamine metabolism-related genes signature tended to be risk factors for the overall survival of cancer patients.


Developmental regulation and cell type-specific expression of the murine gamma F-crystallin gene is mediated through a lens-specific element containing the gamma F-1 binding site.
The mouse gamma F-crystallin gene, one of six differentially regulated members of the gamma-crystallin gene family, is expressed exclusively in central nuclear fiber cells of the adult lens. The expression of this gene is controlled through regulatory elements contained in two upstream enhancers and the proximal promoter. Here we show that while the upstream enhancers and the proximal promoter could each direct gene expression in fiber cells formed at early stages of lens growth and development, cooperation between these elements is required to achieve expression in fiber cells formed at later stages. Evidence is provided that cooperative interaction between these elements modulates gene expression by increasing promoter strength. We also show that sequences within the proximal promoter region that bind lens cell nuclear factor gamma F-1 are sufficient to elicit gene expression in central nuclear fiber cells of the adult lens.


Electronic Flat Band in Distorted Colouring Triangle Lattice.
Dispersionless flat bands (FBs) in momentum space, given rise to electron destructive interference in frustrated lattices, offer opportunities to enhance electronic correlations and host exotic many-body phenomena, such as Wigner crystal, fractional quantum hall state, and superconductivity. Despite successes in theory, great challenges remain in experimentally realizing FBs in frustrated lattices due to thermodynamically structural instability. Here, the observation of electronic FB in a potassium distorted colouring triangle (DCT) lattice is reported, which is supported on a blue phosphorene-gold network. It is verified that the interaction between potassium and the underlayer dominates and stabilizes the frustrated structures. Two-dimensional electron gas is modulated by the DCT lattice, and in turn results in a FB dispersion due to destructive quantum interferences. The FB exhibits suppressed bandwidth with high density of states, which is directly observed by scanning tunneling microscopy and confirmed by the first-principles calculation. This work demonstrates that DCT lattice is a promising platform to study FB physics and explore exotic phenomena of correlation and topological matters.


Family Intervention to Prevent Depression and Substance Use Among Adolescents of Depressed Parents.
Parental depression places offspring at elevated risk for multiple, co-occurring problems. The purpose of this study was to develop and preliminarily evaluate Project Hope, a family intervention for the prevention of both depression and substance use among adolescent-aged children (M = 13.9 years) of depressed parents. The program was created by blending two empirically supported interventions: one for depression and another for substance use. Thirty families were randomly assigned to either Project Hope (n = 16) or a wait-list control condition (n = 14). Pretests, posttests (n = 29), and 5-month follow-ups (n = 28) were conducted separately with parents and youth via phone interviews. Questions asked about the family depression experience, family interactions, family management, coping, adolescent substance use beliefs and refusal skills, adolescent depression, and adolescent substance use. Project Hope was fully developed, manualized, and implemented with a small sample of targeted families. Engagement in the program was relatively high. Preliminary outcome analyses were conducted using 2 (Group) ×3 (Time) analyses of covariance. Results provided some evidence for significant improvements among intervention compared to control participants in indicators of the family depression experience, family management, and coping, and a statistically significant decrease from pretest to posttest in alcohol quantity for intervention compared to control youth. Next steps for this program of research are discussed.


The clinical and histological characteristics and outcomes of drug induced chronic liver injury after removing causative drugs.
To investigate characteristics and outcomes of drug induced chronic liver injury after removing causative drugs. Between Apr 2001 and Mar 2010, patients diagnosed as drug induced liver injury and with chronic courses, were observed. Chronic liver injury was defined as persistent biochemical abnormality for more than 6 months after drugs withdrawal. Forty patients were observed with mean age 41 years and female 28 (70%). Of the 40 patients, 32 (80%) cases showed hepatocellular injury at the onset of liver damage, 4 (10%) cases showed cholestatic injury, and 4 (10%) cases showed mixed injury. Of 32 patients with hepatocellular injury, 24 (75%) cases resemble acute icteric hepatitis at the onset of liver damage. Of 27 patients with hepatocellular injury who underwent liver biopsy, 14 (51.9%) cases showed chronic hepatitis with a mean follow up of 17 months. Of total 40 patients, 15 (37.5%) patients resolved; 18 (45%) cases remained persistent liver injury, 4 (10%) cases developed cirrhosis, 3 (7.5%) cases died. Herbs (45.5%) are the commonest drugs implicated in chronic liver injury. Most cases with drug induced chronic liver injury after removing causative drugs resemble acute icteric hepatitis at the onset of liver damage. Some patients can resolve, some may progress to cirrhosis. Herbs are important drugs for drug induced chronic liver injury.


The catalytic and lectin domains of UDP-GalNAc:polypeptide alpha-N-Acetylgalactosaminyltransferase function in concert to direct glycosylation site selection.
UDP-GalNAc:polypeptide alpha-N-Acetylgalactosaminyltransferases (ppGalNAcTs), a family (EC 184.108.40.206) of enzymes that initiate mucin-type O-glycosylation, are structurally composed of a catalytic domain and a lectin domain. Previous studies have suggested that the lectin domain modulates the glycosylation of glycopeptide substrates and may underlie the strict glycopeptide specificity of some isoforms (ppGalNAcT-7 and -10). Using a set of synthetic peptides and glycopeptides based upon the sequence of the mucin, MUC5AC, we have examined the activity and glycosylation site preference of lectin domain deletion and exchange constructs of the peptide/glycopeptide transferase ppGalNAcT-2 (hT2) and the glycopeptide transferase ppGalNAcT-10 (hT10). We demonstrate that the lectin domain of hT2 directs glycosylation site selection for glycopeptide substrates. Pre-steady-state kinetic measurements show that this effect is attributable to two mechanisms, either lectin domain-aided substrate binding or lectin domain-aided product release following glycosylation. We find that glycosylation of peptide substrates by hT10 requires binding of existing GalNAcs on the substrate to either its catalytic or lectin domain, thereby resulting in its apparent strict glycopeptide specificity. These results highlight the existence of two modes of site selection used by these ppGalNAcTs: local sequence recognition by the catalytic domain and the concerted recognition of distal sites of prior glycosylation together with local sequence binding mediated, respectively, by the lectin and catalytic domains. The latter mode may facilitate the glycosylation of serine or threonine residues, which occur in sequence contexts that would not be efficiently glycosylated by the catalytic domain alone. Local sequence recognition by the catalytic domain differs between hT2 and hT10 in that hT10 requires a pre-existing GalNAc residue while hT2 does not.


Analysis of selection in populations observed over a sequence of consecutive generations : I. Some one locus models with a single, constant fitness component per genotype.
A statistical model is presented for dealing with genotypic frequency data obtained from a single population observed over a run of consecutive generations. This model takes into account possible correlations that exist between generations by conditioning the marginal probability distribution of any one generation on the previously observed generation. Maximum likelihood estimates of the fitness parameters are derived and a hypothesis testing framework developed. The model is very general, and in this paper is applied to random-mating, selfing, parthenogenetic and mixed random-mating and selfing populations with respect to a single locus, g-allele model with constant genotypic fitness differences with all selection occurring either before or after sampling. The assumptions behind this model are contrasted with those of alternative techniques such as minimum chi-square or "unconditional" maximum likelihood estimation when the marginal likelihoods for any one generation are conditioned only on the initial conditions and not the previous generation. The conditional model is most appropriate when the sample size per generation is large either in an absolute sense or in relation to the total population size. Minimum chi-square and the unconditional likelihood are most appropriate when the population size is effectively infinite and the samples are small. Both models are appropriate when the samples are large and the population size is effectively infinite. Under these last conditions, the conditional model may be preferred because it has greater robustness with respect to small deviations from the underlying assumptions and has a greater simplicity of form. Furthermore, if any genetic drift occurs in the experiment, the minimum chi-square and unconditional likelihood approaches can create spurious evidence for selection while the conditional approach will not. Worked examples are presented.


COVID-19 Pandemic and Comparative Health Policy Learning in Iran.
On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus disease (COVID-19) a global pandemic. Starting in December 2019 from China, the first cases were officially announced on February 19 in Qom city, Iran. As of April 3, 2020, 206 countries have reported a total of 932166 cases with 46764 deaths. Along with China, USA, Italy, Spain, and Germany, Iran has been suffering the hardest burden of COVID-19 outbreak. Worse still, countries like Iran are struggling with the double burden of political sanctions to provide lifesaving medical equipment and medicines to combat the emergency. Using systematic document content analysis and through the lenses of health policy triangle, this article aims to compare the policies and strategies that Iran is adopting, with the experience and recommendations of China and WHO to combat COVID-19. Iran has formulated contextual-based policies to combat COVID-19 outbreak before and after virus entrance. Insufficient whole-government, whole-society approach in managing the outbreak, inadequate lifesaving and protective equipment, and delayed decisive governance are the biggest challenges in policy making to combat COVID-19. COVID-19 policies are a public health concern and require professional advocacy attempts through appropriate inter-sectoral collaboration and whole-government coalitions. COVID-19 is an unfolding outbreak; hence, policy learning is crucial to formulate appropriate policies and implement them accordingly. Iran has made many efforts to defeat the outbreak, but more coherent, timely and efficient action is required, now, more than ever, to save lives and slow the spread of this pandemic.


Enhanced Ca(2+)-activated Na(+)-Ca(2+) exchange activity in canine pacing-induced heart failure.
Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) Ca(2+) uptake and a greater dependence on transsarcolemmal Na(+)-Ca(2+) exchange (NCX) for Ca(2+) removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing-induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular Ca(2+) ([Ca(2+)](i)) was buffered to 200 nmol/L. However, when [Ca(2+)](i) was minimally buffered with 50 micromol/L indo-1, Ca(2+) extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and Ca(2+) transport were increased >2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR Ca(2+) uptake, there is an absolute increase in NCX function that depends on [Ca(2+)](i) in the failing heart.


Antimicrobial Effects of AH26 Sealer/Antibiotic Combinations Against Enterococcus Faecalis.
The purpose of this in vitro study was to evaluate the antimicrobial effects of two antibiotics added to AH26 sealer against Enterococcus faecalis (EF). The antimicrobial effects of two antibiotic (amoxicillin and doxycycline) that were added separately to AH26 sealer was evaluated by using the agar diffusion test and in vitro human root inoculation method. The freshly mixed sealers were placed in prepared wells inside agar plates inoculated with EF, and were incubated at 37(°)C. The zones of inhibition were measured at 24, 48, 72 hours and 7 days. Root specimens were prepared and obturated with lateral condensation technique. Samples were collected from infected root canals after 2 and 7 days of incubation and the number of colony-forming units (CFU) was determined. The data were analyzed using one-way and two-way ANOVA. The findings of this study revealed that sealer-antibiotic combination containing amoxicillin and doxycycline had a significant difference in the mean zones of inhibition when compared to AH26 sealer alone in all of the time periods (P<0.05). The minimum effective concentration against EF was one percent of sealer powder weight for both of amoxicillin and doxycyline. The mean log10 CFU in AH26-doxycyline combination group was significantly lower than other groups at 48 h incubation period (P<0.05). AH26-doxycycline combination group and AH26-Amoxicillin combination group killed bacteria (mean CFU=0) in the dentinal tubules at 7 days incubation period. In vitro root fillings carried out with gutta-percha and AH26-antibiotic combination were effective in killing EF in dentinal tubules.


Plasmodium falciparum DDX17 is an RNA helicase crucial for parasite development.
Malaria is one of the major global health concerns still prevailing in this 21st century. Even the effect of artemisinin combination therapies (ACT) have declined and causing more mortality across the globe. Therefore, it is important to understand the basic biology of malaria parasite in order to find novel drug targets. Helicases play important role in nucleic acid metabolism and are components of cellular machinery in various organisms. In this manuscript we have performed the biochemical characterization of homologue of DDX17 from Plasmodium falciparum (PfDDX17). Our results show that PfDDX17 is an active RNA helicase and uses mostly ATP for its function. The qRT-PCR experiment results suggest that PfDDX17 is highly expressed in the trophozoite stage and it is localised mainly in the cytoplasm and in infected RBC (iRBC) membrane mostly in the trophozoite stage. The dsRNA knockdown study suggests that PfDDX17 is important for cell cycle progression. These studies report the biochemical functions of PfDDX17 helicase and further augment the fundamental knowledge about helicase families of P. falciparum.


Total parenteral nutrition in pediatrics: the Borden award address.
Research in parenteral nutrition in infants has proceeded rapidly over the past few years, thanks in large part to the perfection of safe central venous delivery of hypertonic nutritive infusates. At present, there are clear definitions of indications and expectations of results for this method of therapy in two well-defined groups of patients--i.e., selected surgical neonates and infants with chronic intractable diarrhea. In addition, we have suggestive evidence of another potentially valuable application in the nutritional management of very low birthweight infants. However, in this group, a controlled study will be necessary before the role of total parenteral nutrition (TPN) in neonatal care of such infants can be determined precisely. Results obtained with TPN in adults with inflammatory bowel disease or acute renal failure suggest that trials of this technique in pediatric patients with these disorders should be carried out. As a result of the research in TPN carried out thus far, we have learned how to minimize or to treat many of the complications of the technique and we have identified at least the ways by which still others can be prevented. The future holds many new advances not only in the refinement of existing parenteral nutritional solutions but also, and perhaps of even greater importance; in the perfection of individualized total nutritional therapy for specific patients using the enteral route for those discrete components of intake for which digestive and/or absorptive mechanisms are unimpaired and using the parenteral route for the remainder.


Randomized trial of onsite versus referral primary medical care for veterans in addictions treatment.
Patients presenting for treatment of substance use disorders (SUDs) often exhibit medical comorbidities that affect functional health status and healthcare costs. Providing primary care within addictions clinics (onsite care) may improve medical and SUD treatment outcomes in this population. The objective of this study was to compare outcomes among Veterans' Administration (VA) patients who receive medical care within the SUD clinic and those referred to a general medicine clinic at the same facility. Veterans entering SUD treatment with a chronic medical condition and no current primary care were randomized to receive primary medical care: 1) onsite in the VA SUD clinic (n = 358), or 2) in the VA general internal medicine clinic (n = 362). Subjects were assessed at baseline and at 3, 6, and 12 months postrandomization. Intention-to-treat analyses used random-effects regression. Measures included SF-36 Physical and Mental Component Summaries (PCS, MCS), VA service utilization, SUD treatment retention, Addiction Severity Index (ASI) scores, 30-day abstinence, and total VA healthcare costs. Over the study year, patients assigned to onsite care were more likely to attend primary care (adjusted odds ratio [OR] = 2.20; 95% confidence interval [CI] = 1.53-3.15) and to remain engaged in SUD treatment at 3 months (adjusted OR = 1.36; 1.00-1.84). Overall, outcomes on the MCS (but not the PCS) and the ASI improved significantly over time but did not differ by treatment condition. Total VA healthcare costs did not differ reliably across conditions. Compared with referral care, providing primary care within a VA addiction clinic increased primary care access and initial SUD treatment retention but showed no effect on overall health status or costs.


Visual Comparison of Language Model Adaptation.
Neural language models are widely used; however, their model parameters often need to be adapted to the specific domains and tasks of an application, which is time- and resource-consuming. Thus, adapters have recently been introduced as a lightweight alternative for model adaptation. They consist of a small set of task-specific parameters with a reduced training time and simple parameter composition. The simplicity of adapter training and composition comes along with new challenges, such as maintaining an overview of adapter properties and effectively comparing their produced embedding spaces. To help developers overcome these challenges, we provide a twofold contribution. First, in close collaboration with NLP researchers, we conducted a requirement analysis for an approach supporting adapter evaluation and detected, among others, the need for both intrinsic (i.e., embedding similarity-based) and extrinsic (i.e., prediction-based) explanation methods. Second, motivated by the gathered requirements, we designed a flexible visual analytics workspace that enables the comparison of adapter properties. In this paper, we discuss several design iterations and alternatives for interactive, comparative visual explanation methods. Our comparative visualizations show the differences in the adapted embedding vectors and prediction outcomes for diverse human-interpretable concepts (e.g., person names, human qualities). We evaluate our workspace through case studies and show that, for instance, an adapter trained on the language debiasing task according to context-0 (decontextualized) embeddings introduces a new type of bias where words (even gender-independent words such as countries) become more similar to female- than male pronouns. We demonstrate that these are artifacts of context-0 embeddings, and the adapter effectively eliminates the gender information from the contextualized word representations.


The Effect of Outpatient Interventional Audiology on Inpatient Audiology Services.
Although older adults are likely to experience some degree of hearing loss that if untreated will interfere with treatment for other disorders and result in less-than-optimal health care outcomes, health care providers do not have a reliable and cost-effective way to identify these individuals when admitted to a hospital for inpatient care. This article addresses the impact of untreated hearing loss on health care in a hospital setting and shares how the implementation of interventional audiology in an outpatient clinic has impacted the inpatient audiology services provided at a large tertiary care hospital. A discussion of how these services can be further expanded is provided.


The Psychometric Hepatic Encephalopathy Syndrome score does not correlate with blood ammonia, endotoxins or markers of inflammation in patients with cirrhosis.
The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired clearance of gut-derived neurotoxins and increased systemic inflammation are thought to play key roles. The diagnosis is based on detection of neurophysiological and neuropsychometric abnormalities. The Psychometric Hepatic Encephalopathy Score (PHES) have been found to correlate with markers of systematic inflammation including interleukin 6, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). This study explores the associations between the PHES score and systemic inflammation, endotoxins and disease severity using baseline data from a trial involving patients with cirrhosis and minimal or no HE (NCT01769040). Arterial blood was obtained during hepatic vein catheterization, from 54 patients [median age 55 (range, 33-70) years; 83% men] with decompensated but stable cirrhosis. None had clinical evidence of HE but 34 (55.6%) had an abnormal PHES score indicating the presence of minimal HE. Relationships were sought between the PHES score and markers of systemic inflammation, high sensitivity-CRP, cytokines (SDF-1α, TGF-b1, IP-10, IL-6, 10 and 18, and TNF-α; lipopolysaccharide (LPS), the lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14); and the blood ammonia. No significant relationships were found between the PHES score and any of the variables tested with the single exception of the correlation with serum IL-6 (r=-0.29, 95% confidence interval, -0.53 to -0.02, P=0.031). No independent predictors of the PHES score were identified in regression analyses. No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.


Tuberculosis treatment failure and drug resistance--same strain or reinfection?
Tuberculosis patients may have Mycobacterium tuberculosis in their sputum at the end of treatment, and may show new drug resistance, due to either inadequate treatment of the original episode or reinfection with a new strain during therapy. In a cohort study of mineworkers with tuberculosis in South Africa, 57 of 438 patients had positive sputum cultures 6 months after recruitment in 1995. Of the 31 patients who initially had fully sensitive strains, 3 developed multidrug resistance (MDR) and 3 single-drug resistance (SDR). Of the 6 who started with SDR, 3 became MDR. HIV infection was not associated with drug resistance at enrollment or 6 months later. We compared pairs of DNA fingerprints from isolates of M. tuberculosis at recruitment and 6 months later in the 48 patients for whom we had both available. In 45, the pairs were identical. In 1 patient, although both isolates were fully sensitive, the later fingerprint had 1 less band (transposition). In 2 pairs, the fingerprint patterns were completely different: one seemed to be the result of laboratory error and the other was a true reinfection with an MDR strain. Despite a high risk of infection, with a moderate proportion of background drug-resistant strains (11% SDR, 6% MDR), reinfection is not a common cause of treatment failure or drug resistance at 6 months.


[Cardiovascular surgery in a hospital].
The problem of effectuating of a specialized aid to the patients with damages of vessels, enlargement of the patients with cardio- and vessel-diseases, a high lethality and invalidization formed a need for organization of specialized units. The first staff unit of vessel-surgery in the Armed Forces was created in 1968 in CMCH of Vishnevsky A.A. Since 1981 hospital became the main base of preparing vessel-surgeons. The author showed the role of prime specialists in elaborating and development of a new direction in treatment of the patients with cardio- and vessel-damages.


Invasive treatment of non-ST-segment elevation acute coronary syndrome: cardiac catheterization/revascularization for all?
Patients admitted to hospital with symptoms and signs of non-ST-segment elevation acute coronary syndromes have different risk profiles and are in need of an individualized approach that takes into consideration not only age and sex but also comorbidities such as diabetes, renal failure, hypertension, heart failure, peripheral artery disease, earlier revascularization, etc. According to evidence-based medicine and as documented in current guidelines, there is currently evidence for early catheterization and, if feasible, revascularization in high-risk patients, especially in men. Nevertheless, because of a lack of definitive evidence, there is uncertainty about treating women in the same way. Because women are usually older and have more comorbidities, they are frailer and revascularization should be indicated with greater caution. There is no evidence that catheterization as such is worse for women than for men; however, for both men and women with low risk, a less invasive approach, such as coronary computed tomography angiography, could be considered as a first diagnostic tool.


New, simple insulin-receptor assay with universal application to solubilized insulin receptors and receptors in broken and intact cells.
A new, simple insulin-receptor-binding assay has been devised. The assay is based on the separation of free and receptor-bound 125I-labeled insulin in 80% ethanol. It was found that the insulin-receptor complex was fully stable at this ethanol concentration, regardless of the source of the receptor employed. The assay has been evaluated with solubilized insulin receptors and membrane-bound receptors from human placenta and porcine liver as well as intact cells with the IM-9 cell line. The assay is simple, rapid, and has large capacity. Comparisons of the ethanol-based assay to the conventionally employed assays with polyethylene glycol or microfuge centrifugation for the separation of free and bound 125I-insulin revealed large discrepancies between the assays. The ethanol-based assay always appeared to provide a better separation. Microfuge centrifugation of placental membranes precipitated approximately 3% of the ethanol-precipitable insulin-receptor complex, while polyethylene glycol precipitation of solubilized insulin receptors varied between 40 and 80% of the ethanol precipitability, depending on the receptor concentration employed.


Neuregulin-4 is associated with plasma glucose and increased risk of type 2 diabetes mellitus.
Neuregulin-4 is a cytokine with many functions and is primarily produced by fat tissue. The aim of the study was to observe the relationship between serum neuregulin-4 levels and diabetes regulation in type 2 diabetes mellitus (T2DM), and to compare neuregulin-4 levels of diabetic subjects with those in healthy controls. Patients with T2DM were included to the study. Healthy subjects were enrolled as controls. Subjects with T2DM with glycated haemoglobin (HbA1c) <7% were classed as well controlled and those with HbA1c >7% were classed as poorly controlled. Neuregulin-4 levels of the study and control groups were compared. The neuregulin-4 levels of the poorly controlled T2DM, well-controlled T2DM and control groups were significantly different (p = 0.005). Neuregulin-4 was significantly correlated with fasting plasma glucose (r = 0.247, p = 0.002) but not with HbA1c. In a regression analysis model, 0.1 point elevation in neuregulin-4 levels increased the rate of existence of T2DM 4.4-fold (odds ratio 4.4, 95% confidence interval 1.26-15.1; p = 0.02). Neuregulin-4 is significantly increased in patients with T2DM compared with control subjects, which means that it could be a marker of T2DM. Since neuregulin-4 was correlated with fasting glucose, we suggest that elevated neuregulin-4 could predict poor control in T2DM for short periods when HbA1c is not useful.  Moreover, one unit elevation in neuregulin-4 (0.1 ng/ml) increases the rate of existence of T2DM 4.4-fold, independently from other variables.


Influence of pharmacist intervention, based on CMO model, to improve activation in HIV patients.
The aim of study was to evaluate the influence of pharmacist intervention based on "CMO model", to improve activation in HIV-patients. Longitudinal, prospective, single-center study. Eligible patients were HIV-infected, taking antiretroviral treatment. The collected data included demographic characteristics, clinical and HIV-related and pharmacotherapeutic variables. The primary outcome was the variation of patient activation measured by Spanish adapted patient activation measure questionnaire. This questionnaire assesses people's knowledge, skills and confidence in managing their own health care. The assessment was performed at the beginning and 6 months after the program start, which consisted of individualized interventions planned in the stratification model, a motivational interview and a specific pharmacotherapeutic follow-up. A total of 140 patients were included. The most common regimens prescribed were based on non-nucleoside plus nucleoside reverse transcriptase inhibitor (44.0%) and more than half of the patients had chronic concomitant medication. The patients who achieved the highest activation level increased from 28.1% to 68.3% (p<0.0005). The relationship between this increase in patient activation and the stratification level that occurs in largest increases in patients with a low need level, where it was observed an improvement in the percentage of patients with high activation from 28.3% to 74.3% (p<0.001) after intervention. The percentage of patients with adequate adherence to concomitant treatment increased by 18.4% (p = 0.035). Baseline PAM values showed high activation for 28.6% (40 patients), intermediate for 43.6% (61) and low for 27.9% (39). CMO model has an important role for patient activation, improving adherence and health outcomes for HIV+ patients.


IL-1β enhances cell viability and decreases 5-FU sensitivity in novel colon cancer cell lines derived from African American patients.
In the U.S., African Americans (AAs) present with the highest incidence and mortality rates for Colorectal Cancer (CRC). When compared to Caucasian American (CA) patients, AAs also have reduced response to the first line standard of care chemotherapeutic agent 5-Fluorouracil (5-FU). Previously, we observed differential gene expression between the two populations, suggesting that colon tumors from AA patients display a decreased antitumor immune response and an increased expression of genes encoding proteins involved in inflammatory processes, such as Interleukin-1β (IL-1β). Here, we investigate the role of IL-1β in modifying chemotherapeutic response and altering expression of proteins in novel AA and well-established CA colon cancer cell lines. RNA sequencing analysis was performed to detect expression of genes involved in inflammation in AA and CA colon cancer cells. The effects of IL-1β on 5-FU response was evaluated by assessing cell viability (MTS assay) and apoptosis (flow cytometry analysis) following treatment with 5-FU alone or in combination with the cytokine. Further, we used an IL-1 receptor antagonist (IL-1Ra) to inhibit IL-1β-induced effects on 5-FU sensitivity and NF-kB pathway activation. AA colon cancer cell lines present significant increase in expression of genes IL1R2 (373-fold change (FC), IRAK1 (3.24 FC), IKBKB, (5.33 FC) NF-KB IA (5.95 FC), MYD88, (3.72 FC), IRAK3 (161 FC), TRAF5 (4.1 FC). A significant decrease in the response to 5-FU treatment, as well as a significant increase in phosphorylation of IκBα and secretion of IL-8, was seen following IL-1β treatment, in both AA and CA cell lines. Finally, treatment with IL-1Ra was able to reverse the effects induced by IL-1β, by increasing the cells sensitivity to 5-FU. IL-1Ra also inhibited phosphorylation of IκBα and IL-8 secretion. Our results suggest a differential expression of inflammatory genes and proteins that might regulate the different response to IL-1β between AA and CA colon cancer cell lines. Our data also demonstrates that IL-1β is involved in modulating 5-FU response in both AA and CA colon cancer cell lines. Further investigation of these mechanisms might help elucidate the differences seen in incidence, mortality and response to therapy in AA colon cancer patients.


Constructing Mixed Density Functionals for Describing Dissociative Chemisorption on Metal Surfaces: Basic Principles.
The production of a majority of chemicals involves heterogeneous catalysis at some stage, and the rates of many heterogeneously catalyzed processes are governed by transition states for dissociative chemisorption on metals. Accurate values of barrier heights for dissociative chemisorption on metals are therefore important to benchmarking electronic structure theory in general and density functionals in particular. Such accurate barriers can be obtained using the semiempirical specific reaction parameter (SRP) approach to density functional theory. However, this approach has thus far been rather ad hoc in its choice of the generic expression of the SRP functional to be used, and there is a need for better heuristic approaches to determining the mixing parameters contained in such expressions. Here we address these two issues. We investigate the ability of several mixed, parametrized density functional expressions combining exchange at the generalized gradient approximation (GGA) level with either GGA or nonlocal correlation to reproduce barrier heights for dissociative chemisorption on metal surfaces. For this, seven expressions of such mixed density functionals are tested on a database consisting of results for 16 systems taken from a recently published slightly larger database called SBH17. Three expressions are derived that exhibit high tunability and use correlation functionals that are either of the PBE GGA form or of one of two limiting nonlocal forms also describing the attractive van der Waals interaction in an approximate way. We also find that, for mixed density functionals incorporating GGA correlation, the optimum fraction of repulsive RPBE GGA exchange obtained with a specific GGA density functional is correlated with the charge-transfer parameter, which is equal to the difference in the work function of the metal surface and the electron affinity of the molecule. However, the correlation is generally not large and not large enough to obtain accurate guesses of the mixing parameter for the systems considered, suggesting that it does not give rise to a very effective search strategy.


Time-Domain Nuclear Magnetic Resonance Investigation of Water Dynamics in Different Ginger Cultivars.
Different ginger cultivars may contain different nutritional and medicinal values. In this study, a time-domain nuclear magnetic resonance method was employed to study water dynamics in different ginger cultivars. Significant differences in transverse relaxation time T2 values assigned to the distribution of water in different parts of the plant were observed between Henan ginger and four other ginger cultivars. Ion concentration and metabolic analysis showed similar differences in Mn ion concentrations and organic solutes among the different ginger cultivars, respectively. On the basis of Pearson's correlation analysis, many organic solutes and 6-gingerol, the main active substance of ginger, exhibited significant correlations with water distribution as determined by NMR T2 relaxation, suggesting that the organic solute differences may impact water distribution. Our work demonstrates that low-field NMR relaxometry provides useful information about water dynamics in different ginger cultivars as affected by the presence of different organic solutes.


Associations between multimorbidity burden and Alzheimer's pathology in older adults without dementia: the CABLE study.
Studies have shown that multimorbidity may be associated with the Alzheimer's disease (AD) stages, but it has not been fully characterized in patients without dementia. A total of 1402 Han Chinese older adults without dementia from Chinese Alzheimer's Biomarker and LifestylE (CABLE) study were included and grouped according to their multimorbidity patterns, defined by the number of chronic disorders and cluster analysis. Multivariable linear regression models were used to detect the associations with AD-related cerebrospinal fluid (CSF) biomarkers. Multimorbidity and severe multimorbidity (≥4 chronic conditions) were significantly associated with CSF amyloid and tau levels (pFDR < 0.05). Metabolic patterns were significantly associated with higher levels of CSF Aβ40 (β = 0.159, pFDR = 0.036) and tau (P-tau: β = 0.132, pFDR = 0.035; T-tau: β = 0.126, pFDR = 0.035). The above associations were only significant in the cognitively normal (CN) group. Multimorbidity was associated with brain AD pathology before any symptomatic evidence of cognitive impairment. Identifying such high-risk groups might allow tailored interventions for AD prevention.


Uptake, tissue distribution, and depuration of total silver in common carp (Cyprinus carpio) after aqueous exposure to silver nanoparticles.
The increased use and disposal of silver nanoparticles (AgNPs) has led to their release from wastewater treatment plants into surface waters and concern over potential for negative effects in aquatic organisms. Investigations of the toxicity of AgNPs in fish have considered various species, exposure routes, and test end points; however, the toxicokinetics of total silver has not been studied in fish exposed to aqueous AgNPs. In this study, we investigated the toxicokinetics of total silver in common carp (Cayprinus carpio) exposed to AgNPs [0.62 ± 0.12 (mean ± standard deviation) mg L(-1)] for 7 days followed by a 2 week depuration period. During exposure and depuration, fish were sampled, tissues were excised (gills, brain, skeletal muscle, gastrointestinal tract, liver, and blood) and digested in acid, and total silver concentrations were analyzed by inductively coupled plasma-optical emission spectrometry. Total silver in tissues increased during the 7 day exposure, and mean concentrations were 5.61 mg/kg of liver, 3.32 mg/kg of gills, 2.93 mg/kg of gastrointestinal tract, 0.48 mg/kg of skeletal muscle, 0.14 mg/kg of brain, and 0.02 mg/kg of blood. Transmission electron microscopy energy-dispersive spectroscopy confirmed the presence of silver in the tissues. After depuration for 14 days, total silver returned to control levels in all tissues except liver (4.22 mg/kg), gastrointestinal tract (1.26 mg/kg), and gills (0.77 mg/kg).


Capsaicin regulates voltage-dependent sodium channels by altering lipid bilayer elasticity.
At submicromolar concentrations, capsaicin specifically activates the TRPV1 receptor involved in nociception. At micro- to millimolar concentrations, commonly used in clinical and in vitro studies, capsaicin also modulates the function of a large number of seemingly unrelated membrane proteins, many of which are similarly modulated by the capsaicin antagonist capsazepine. The mechanism(s) underlying this widespread regulation of protein function are not understood. We investigated whether capsaicin could regulate membrane protein function by changing the elasticity of the host lipid bilayer. This was done by studying capsaicin's effects on lipid bilayer stiffness, measured using gramicidin A (gA) channels as molecular force-transducers, and on voltage-dependent sodium channels (VDSC) known to be regulated by bilayer elasticity. Capsaicin and capsazepine (10-100 microM) increase gA channel appearance rate and lifetime without measurably altering bilayer thickness or channel conductance, meaning that the changes in bilayer elasticity are sufficient to alter the conformation of an embedded protein. Capsaicin and capsazepine promote VDSC inactivation, similar to other amphiphiles that decrease bilayer stiffness, producing use-dependent current inhibition. For capsaicin, the quantitative relation between the decrease in bilayer stiffness and the hyperpolarizing shift in inactivation conforms to that previously found for other amphiphiles. Capsaicin's effects on gA channels and VDSC are similar to those of Triton X-100, although these amphiphiles promote opposite lipid monolayer curvature. We conclude that capsaicin can regulate VDSC function by altering bilayer elasticity. This mechanism may underlie the promiscuous regulation of membrane protein function by capsaicin and capsazepine-and by amphiphilic drugs generally.


The application of amplicon length heterogeneity PCR (LH-PCR) for monitoring the dynamics of soil microbial communities associated with cadaver decomposition.
The placement of cadavers in shallow, clandestine graves may alter the microbial and geochemical composition of the underlying and adjacent soils. Using amplicon length heterogeneity-PCR (LH-PCR) the microbial community changes in these soils can be assessed. In this investigation, nine different grave sites were examined over a period of 16weeks. The results indicated that measurable changes occurred in the soil bacterial community during the decomposition process. In this study, amplicons corresponding to anaerobic bacteria, not indigenous to the soil, were shown to produce differences between grave sites and control soils. Among the bacteria linked to these amplicons are those that are most often part of the commensal flora of the intestines, mouth and skin. In addition, over the 16week sampling interval, the level of indicator organisms (i.e., nitrogen fixing bacteria) dropped as the body decomposed and after four weeks of environmental exposure they began to increase again; thus differences in the abundance of nitrogen fixing bacteria were also found to contribute to the variation between controls and grave soils. These results were verified using primers that specifically targeted the nifH gene coding for nitrogenase reductase. LH-PCR provides a fast, robust and reproducible method to measure microbial changes in soil and could be used to determine potential cadaveric contact in a given area. The results obtained with this method could ultimately provide leads to investigators in criminal or missing person scenarios and allow for further analysis using human specific DNA assays to establish the identity of the buried body.


A three-year clinical caries evaluation of the effect of a sodium fluoride-silica abrasive dentifrice.
This study was conducted to determine if the anticaries effectiveness of a 0.243% sodium fluoride-silica abrasive dentifrice is superior to a 0.4% stannous fluoride-calcium pyrophosphate dentifrice. A nonfluoride, calcium pyrophosphate abrasive placebo dentifrice was also included at one-third the sample size of the active treatment groups to estimate the level of efficacy of the sodium fluoride dentifrice. A total of 3,093 schoolchildren were randomly assigned at a ratio of 3:3:1 to the sodium fluoride dentifrice, the stannous fluoride dentifrice, or the placebo dentifrice, respectively. Caries examinations were made by the same examiner initially and after one, two, and three years of ad libitum product usage. After three years, the results showed that the group using the sodium fluoride dentifrice had significantly fewer DMF teeth and DMF surfaces increments than the group using the stannous fluoride dentifrice. The percent reductions for DMF teeth and DMF surfaces were 24.2% and 22.6%, respectively. Both groups using fluoride dentifrices also had significantly fewer DMF teeth and DMF surfaces increments than the group using the placebo dentifrice.


Time-Resolved X-ray Observation of Intracellular Crystallized Protein in Living Animal.
Understanding the cellular environment as molecular crowding that supports the structure-specific functional expression of biomolecules has recently attracted much attention. Time-resolved X-ray observations have the remarkable capability to capture the structural dynamics of biomolecules with subnanometre precision. Nevertheless, the measurement of the intracellular dynamics within live organisms remains a challenge. Here, we explore the potential of utilizing crystallized proteins that spontaneously form intracellular crystals to investigate their intracellular dynamics via time-resolved X-ray observations. We generated transgenic Caenorhabditis elegans specifically expressing the crystallized protein in cells and observed the formation of the protein aggregates within the animal cells. From the toxic-effect observations, the aggregates had minimal toxic effects on living animals. Fluorescence observations showed a significant suppression of the translational diffusion movements in molecules constituting the aggregates. Moreover, X-ray diffraction measurements provided diffraction signals originating from these molecules. We also observed the blinking behaviour of the diffraction spots, indicating the rotational motion of these crystals within the animal cells. A diffracted X-ray blinking (DXB) analysis estimated the rotational motion of the protein crystals on the subnanometre scale. Our results provide a time-resolved X-ray diffraction technique for the monitoring of intracellular dynamics.


Opposite sex-specific effects of Wolbachia and interference with the sex determination of its host Ostrinia scapulalis.
In the adzuki bean borer, Ostrinia scapulalis, the sex ratio in most progenies is 1 : 1. Females from Wolbachia-infected matrilines, however, give rise to all-female broods when infected and to all-male broods when cured of the infection. These observations had been interpreted as Wolbachia-induced feminization of genetic males into functional females. Here, we show that the interpretation is incorrect. Females from both lines have a female karyotype with a WZ sex-chromosome constitution while males are ZZ. At the time of hatching from eggs, WZ and ZZ individuals are present at a 1 : 1 ratio in broods from uninfected, infected and cured females. In broods from Wolbachia-infected females, ZZ individuals die during larval development, whereas in those from cured females, WZ individuals die. Hence, development of ZZ individuals is impaired by Wolbachia but development of WZ females may require the presence of Wolbachia in infected matrilines. Sexual mosaics generated (i) by transfection of uninfected eggs and (ii) by tetracycline treatment of Wolbachia-infected mothers prior to oviposition were ZZ in all tissues, including typically female organs. We conclude that: (i) Wolbachia acts by manipulating the sex determination of its host; and (ii) although sexual mosaics can survive, development of a normal female is incompatible with a ZZ genotype.


Prospective registration of all patients in a geographical region with newly diagnosed bladder carcinomas during a two-year period.
To report the age, stage and grade of all patients with newly diagnosed bladder carcinoma in a well-defined geographical region and to compare this cohort with previous reports which come mainly from large referral centres. All newly diagnosed bladder carcinoma patients (n = 701) in Western Sweden were prospectively registered during a 2-year period (1987-88). The histopathological material was re-examined by a reference pathologist. All the original clinical records were reviewed by one urologist 5-7 years after diagnosis. Demographic data, tumor grade, stage, multiplicity, presence of carcinoma in situ and lymphatic invasion are presented. The mean age at diagnosis was 70.5 years. Grade and stage increase with age. The proportion of non-invasive tumors (55%) is higher than in any previous Scandinavian report. The age-standardized incidence in bladder carcinoma among men in the largest city (Göteborg) is 55% higher than in the rest of the region (p<0.0001). Deviations between the primary pathologist and the reviewer with regard to tumor grade were particularly seen in tumors of grades I and II. Differences in mean age, stage and grade distribution were found between the present report, which included all patients with newly diagnosed bladder carcinoma in a geographical area, and other reports, which mainly comprised patients from large treatment centres. These differences can probably and mainly be explained by selection factors such as various degrees of inclusion of low-grade papillary tumors.


Quantifying the speed of fluctuations in systolic blood pressure.
Increased blood pressure variability (BPV), even in the absence of hypertension, has been identified as an important independent cardiovascular risk factor (CVRF). However, the role of the speed of changes in systolic blood pressure (SBP; vSBP) on cardiovascular risk needs to be investigated. The objective of this study was to investigate whether subjects with a high cardiovascular risk profile have an increased degree and speed of changes in SBP compared with subjects with low or no risk. Resting beat-to-beat blood pressure (BP) was recorded for 5 min. Standard BPV measures in both time and frequency domains were conducted. The s.d. of SBP (s.d.-SBP) values was used to quantify the degree of BPV. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different interbeat intervals (IBI). Subjects were allocated to one of four groups according to the number of CVRFs (0, 1, 2, ≥ 3 CVRF). Of 122 subjects, 19.7% had 0 CVRF, 27.0% had 1, 32.0% had 2 and 21.3% had ≥ 3 CVRFs. There was an increase in vSBP across the four risk groups. The vSBP in patients without CVRF was 3.12 (1.09), 1 CVRF 3.23 (1.07), 2 CVRF 4.16 (2.26) and ≥ 3 CVRF 4.22 (1.66; P = 0.015). The s.d.-SBP was not significantly different between the cardiovascular risk groups. The speed of fluctuations in SBP rather than the degree of BPV is pronounced in patients with elevated cardiovascular risk. Increased speed of BP fluctuations may thus be a contributing mechanism to cardiovascular morbidity.


The impact of apoptosis and inflammation gene polymorphisms on transplanted kidney function.
The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function. A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing. Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86). This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.


Structural configurations and Raman spectra of carbon nanoscrolls.
Three types of carbon nanoscroll (CNS) structures that are formed when scrolling up graphene sheets are investigated using Raman spectroscopy and atomic force microscopy (AFM). The CNSs were produced from exfoliated monolayer graphene deposited on a Si chip by applying a droplet of isopropyl alcohol (IPA) solution. The three types of CNS are classified as single-elliptical-core, double-elliptical-core (both with large internal volumes) and collapsed ribbon-like, based on AFM surface profile measurements. We discuss the structure and formation of CNS with much larger hollow cores than is commonly assumed and relate this to the large effective 2D bending stiffness of graphene in the IPA solution. The large elliptical core structures show Raman spectra similar to those previously reported for CNS and indicate little interaction between the scrolled layers. The Raman spectra from ribbon-like structures show additional features that are similar to that of folded graphene. These new features can be related to layer breathing modes combined with some resonance enhancement at specific regions of the ribbon-like CNSs that are due to specific twist angles produced when the structure folds/collapses.


Hydrogen Bond-Enabled Heterolytic and Homolytic Peroxide Activation within Nonheme Copper(II)-Alkylperoxo Complexes.
To explore the reactivity of copper-alkylperoxo species enabled by the heterolytic peroxide activation, room-temperature stable mononuclear nonheme copper(II)-alkylperoxo complexes bearing a N-(2-ethoxyethanol)-bis(2-picolyl)amine ligand (HN3O2), [CuII(OOR)(HN3O2)]+ (R = cumyl or tBu), were synthesized and spectroscopically characterized. A combined experimental and computational investigation on the reactivity and reaction mechanisms in the phosphorus oxidation, C-H bond activation, and aldehyde deformylation reactions by the copper(II)-alkylperoxo complexes has been conducted. DFT-optimized structures suggested that a hydrogen bonding interaction exists between the ethoxyethanol backbone of the HN3O2 ligand and either the proximal or distal oxygen atom of the alkylperoxide moiety, and this interaction consequently results in the enhanced stability of the copper(II)-alkylperoxo species. In the phosphorus oxidation reaction, both experimental and computational results indicated that a phosphine-triggered heterolytic O-O bond cleavage occurred to yield phosphine oxide and alcohol products. DFT calculations suggested that (i) the H-bonding between the ethoxyethanol backbone and distal oxygen of the alkylperoxide moiety and (ii) the phosphine binding to the proximal oxygen of the alkylperoxide moiety engendered the heterolytic peroxide activation. In the C-H bond activation reactions, temperature-dependent reactivity of the copper(II)-alkylperoxo complexes was observed, and a relatively strong activation energy of 95 kcal mol-1 was required to promote the homolytic peroxide activation. A rate-limiting hydrogen atom abstraction reaction of xanthene by the putative copper(II)-oxyl radical resulted in the formation of the dimeric copper product and the substrate radical that further underwent autocatalytic oxidation reactions to form an oxygen incorporated product. Finally, amphoteric reactivity of copper(II)-alkylperoxo complexes has been assessed by conducting kinetic studies and product analysis of the aldehyde deformylation reaction.


Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.
p63 is proposed to play roles in normal development and differentiation of stratified epithelia including urothelium. We recently reported that impaired p63 expression is a common feature of high-grade invasive urothelial carcinomas and associates with reduced beta-catenin. On the basis of these facts, we proposed that impaired p63 expression contributes to biological aggressiveness of urothelial neoplasms. Uroplakin (UP) III expression was also evaluated to investigate a possible association between loss of p63 expression and terminal urothelial differentiation. Expression of p63, beta-catenin, and UP III was immunohistochemically analyzed in 75 cystectomy specimens of high-grade invasive bladder carcinoma. p63 expression was semiquantified and compared with pathological parameters, expression of beta-catenin and UP III, and cancer-specific survival. Lower p63 expression was significantly associated with higher Tumor-Node-Metastasis (TNM) stage (P = 0.0004), lymph-node metastasis (P = 0.013), and reduced beta-catenin expression (P = 0.003). By univariate analysis, lower p63 expression, along with TNM stage and lymph-node status, were significantly associated with a poor prognosis (P = 0.0005), whereas reduced beta-catenin was not. By multivariate analysis, the prognostic effect of p63 expression was independent of TNM stage and lymph-node status with marginal statistical significance (P = 0.074). UP III expression was restricted to a subset of p63-negative carcinoma cells, including even anaplastic carcinoma cells. Impaired p63 expression characterizes biological aggressiveness of high-grade invasive urothelial carcinomas. Moreover, loss of p63 expression is a prerequisite for UP III expression. Our data suggest that p63 plays critical roles in tumor progression and biochemical terminal differentiation of urothelial neoplasms.


[Adrenal carcinoma. Clinical and anatomopathological prognostic factors].
We performed on 9 patients with adrenal cortical carcinoma a retrospective study during 1967-1995 to evaluate the most important prognostic factors. Four patients were males and five females (mean age: 40.3 years). Five patients had endocrine symptoms (55%) and four had "non-functioning" tumors (45%). The tumor involved the left adrenal gland in 5 cases and the right in 4. The mean diameter of the neoplasm was 9.5 cm, with a mean weight of 411 g. The average duration of symptoms before diagnosis was 7.3 months. One patient had invasion of the inferior vena cava with liver metastases. Eight patients underwent curative surgery, the median survival time was 13.7 months, only 1 patient is alive after 18 months from surgical resection. We concluded that adrenal carcinomas have poor prognosis; staging and grading of the neoplasm, and age of the patient at diagnosis are predictors of survival.


DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest.
Vpr-mediated induction of G2 cell cycle arrest has been postulated to be important for human immunodeficiency virus type 1 (HIV-1) replication, but the precise role of Vpr in this cell cycle arrest is unclear. In the present study, we have shown that HIV-1 Vpr interacts with damaged DNA binding protein 1 (DDB1) but not its partner DDB2. The interaction of Vpr with DDB1 was inhibited when DCAF1 (VprBP) expression was reduced by short interfering RNA (siRNA) treatment. The Vpr mutant (Q65R) that was defective for DCAF1 interaction also had a defect in DDB1 binding. However, Vpr binding to DDB1 was not sufficient to induce G2 arrest. A reduction in DDB1 or DDB2 expression in the absence of Vpr also did not induce G2 arrest. On the other hand, Vpr-induced G2 arrest was impaired when the intracellular level of DDB1 or Cullin 4A was reduced by siRNA treatment. Furthermore, Vpr-induced G2 arrest was largely abolished by a proteasome inhibitor. These data suggest that Vpr assembles with DDB1 through interaction with DCAF1 to form an E3 ubiquitin ligase that targets cellular substrates for proteasome-mediated degradation and G2 arrest.


The role of head movements in the control of manual prehension.
Binocular information has been shown to be important for the programming and control of reaching and grasping. But even without binocular vision, people are still able to reach out and pick up objects accurately - albeit less efficiently. As part of a continuing investigation into the role that monocular cues play in visuomotor control, we examined whether or not subjects could use retinal motion information, derived from movements of the head, to help program and control reaching and grasping movements when binocular vision is denied. Subjects reached out in the dark to an illuminated sphere presented at eye-level, under both monocular and binocular viewing conditions with their head either free to move or restrained. When subjects viewed the display monocularly, they showed fewer on-line corrections when they were allowed to move their head. No such difference in performance was seen when subjects were allowed a full binocular view. This study, combined with previous work with neurological patients, confirms that the visuomotor system "prefers" to use binocular vision but, when this information is not available, can fall back on other monocular depth cues, such as information produced by motion of the object (and the scene) on the retina, to help program and control manual prehension.


The effects of COVID-19 on food insecurity, financial vulnerability and housing insecurity among women and girls living with or at risk of HIV in Nigeria.
Aim: Women and girls living with or at high risk of acquiring HIV (WGL&RHIV) in Africa are economically vulnerable. This study aims to advance understanding of the economic impact of COVID-19 on WGL&RHIV and to identify the factors associated with this insecurity.Methods: Data were collected from a cross-sectional survey conducted among a convenience sample of WGL&RHIV in Nigeria between May and September 2021. Logistic regressions enabled the study of the role of HIV status, mental health and macrosocial characteristics (people with disability, transgender women, sex workers, persons engaged in transactional sex, substance users, and people on the move) on economic vulnerability, measured by food, financial and housing insecurity, since the COVID-19 pandemic began. The model accounted for the possible interactions between the macrosocial characteristics and controlled for confounders.Results: There were 3 313 (76.1%) of 4 355 respondents facing food insecurity, 3 664 (83.6%) of 4 385 with financial vulnerability and 1 282 (36.2%) of 3 544 with housing insecurity. Being a member of the key and vulnerable groups was strongly associated with food insecurity, financial vulnerability and housing insecurity, regardless of HIV serostatus. For example, WGL&RHIV engaging in transactional sex were more than four times more likely (aOR 4.42; 95% CI 2.57-7.59) to face housing insecurity and more than twice more likely to face food insecurity (aOR 2.47, 95% CI 1.35-4.52) and financial vulnerability (aOR 2.87, 95% CI 1.39-5.93). This economic vulnerability may reduce their negotiating power for safer sex or the use of HIV prevention methods, exposing them to increased risks of HIV infection. Poor mental health was also associated with the three forms of economic vulnerability.Conclusions: As the long-term impact of the COVID-19 crisis on African economies unfolds, HIV programmes at the country level must include economic vulnerability and mental unwellness mitigation activities for WGL&RHIV.


The left-sided aortic arch in humans, viewed as the end-result of natural selection during vertebrate evolution.
At some point during vertebrate evolution from species dwelling in water to living on land, the ancestral double or right aortic arches became single and left-sided in mammals, including humans, as the result of synchronous developments in cardiovascular and respiratory embryogenesis. Since left-sided aortic arches are unique to mammals, hemodynamics related to the placenta, specifically the requirement for a large arterial duct connecting to the descending aorta, may have led to switching from the right-sided to the left-sided arch. Additionally, development of a trilobar right lung and its bronchial tree, also unique to mammalian evolution, restricted the space above the high eparterial bronchus to a single large vessel. Consequently, mammals that mutated to the left-sided aortic arch avoided respiratory, digestive or circulatory problems that are often associated with an isolated right-sided aortic arch--something which could be considered a successful mistake. Due to natural selection, and survival of the fittest, the left-sided arch became the norm in mammals. In congenital cardiac malformations where a large arterial duct is not mandatory in fetal life, as in Fallot's tetralogy or common arterial trunk, a right-sided aortic arch continues to occur, perhaps as an atavistic reversion to the anatomy seen in ancestral vertebrates.


Foot Typology, Dynamic and Static Weight Distribution, and Radiographic Changes After Subtalar Arthroereisis in Juvenile Symptomatic Flexible Flat Feet.
Flexible flatfoot is among the most common skeletal disorders in childhood. This study describes the dynamic and static correction effects of subtalar arthroereisis in adolescents with flexible symptomatic flatfeet in comparison to normal subjects as well as to results before and after removal of metal. Eighteen adolescents with 25 symptomatic flexible flatfeet were treated surgically with a subtalar arthroereisis at a mean of 12.5 (10-16) years. At follow-up (mean 3.9 years, range 0.4-8), patients filled out the American Orthopaedic Foot and Ankle Society questionnaire, received radiographs and were examined using dynamic and static pedobarography as well as static hindfoot axis examination. Results were compared to healthy controls (n = 13; 26 feet). Surgically treated feet (n = 25) had better questionnaire results after surgery than before, but lower scores than healthy feet. Radiological parameters improved significantly after surgery. Removal of metal did not influence post-surgical results (follow-up 2.8 years). Surgically treated feet had larger contact areas than normal feet with predominance to the midfoot region. The relative maximum force, relative peak pressure and contact time were higher in the midfoot of treated feet compared to controls. When comparing pedobarography data of treated versus untreated feet of the same patients (subgroup n = 11 feet), there were no differences. Subtalar arthroereisis was able to effectively treat symptomatic flexible flatfeet in this population. Results improved significantly evaluating a questionnaire, radiographs, dynamic and static weight distribution, but were still worse than results of healthy feet. There was no relapse after removal of metal.


Long-term potentiation trains induce mossy fiber sprouting.
It has been shown that both amygdaloid and hippocampal kindling induce sprouting of the mossy fibers in the dentate gyrus. In this study, we investigated whether non-epileptogenic stimulation could also induce mossy fiber sprouting. Long-term potentiation (LTP) was induced in the dentate gyrus by the application of brief, high frequency trains to the perforant path. The potentiating stimulation was applied each day for 10 days, and the tissue was prepared for Timm labelling 7 days later. Sprouting was significantly increased in the LTP group compared to the implanted control rats. These results suggest that mossy fiber sprouting is not damage-induced and is dependent on neuronal activation.


Ribonucleases and bacterial virulence.
Bacterial stress responses provide them the opportunity to survive hostile environments, proliferate and potentially cause diseases in humans and animals. The way in which pathogenic bacteria interact with host immune cells triggers a complicated series of events that include rapid genetic re-programming in response to the various host conditions encountered. Viewed in this light, the bacterial host-cell induced stress response (HCISR) is similar to any other well-characterized environmental stress to which bacteria must respond by upregulating a group of specific stress-responsive genes. Post stress, bacteria must resume their pre-stress genetic program, and, as a consequence, must degrade unnecessary stress responsive transcripts through RNA decay mechanisms. Further, there is a well-established role for several ribonucleases in the cold shock response whereby they modulate the changing transcript landscape in response to the stress, and during acclimation and subsequent genetic re-programming post stress. Recently, ribonucleases have been implicated as virulence-associated factors in several notable Gram-negative pathogens including, the yersiniae, the salmonellae, Helicobacter pylori, Shigella flexneri and Aeromonas hydrophila. This review will focus on the roles played by ribonucleases in bacterial virulence, other bacterial stress responses, and on their novel therapeutic applications.


Cystoid macular edema associated with latanoprost therapy in a pseudophakic vitrectomized patient after removal of silicone oil endotamponade.
To describe the occurrence of cystoid macular edema in a pseudophakic vitrectomized patient following use of latanoprost (0.005%). A 58-year-old patient underwent routine cataract surgery with posterior chamber lens implantation complicated by rhegmatogenous retinal detachment three months later. A pars plana vitrectomy was performed with silicone oil endotamponade which was removed six months later. Five months after oil removal, the patient presented with secondary open-angle glaucoma treated with latanoprost 0.005% eye drops once daily. Two weeks after initiation of latanoprost treatment, visual acuity dropped from 0.8 to 0.3 due to cystoid macular edema confirmed by fluorescein angiography. After discontinuing latanoprost therapy and with topical corticosteroid treatment, cystoid macular edema slowly resolved, and within 6 months, visual acuity improved to 0.8. Despite its marked ocular hypotensive effect, latanoprost should be carefully used in patients after uncomplicated cataract surgery if the vitreous body was removed by pars piana vitrectomy.


Depressive symptoms, alcohol and other drug use, and suicide risk: Prevention and treatment effects from a two-country online eating disorder risk reduction trial.
Eating disorders are known to have high comorbidity, and the current report outlines the impact of an online eating disorder risk reduction program on brief, self-report measures of depressive symptoms, alcohol and other drug use, and suicidality. An online pragmatic, randomized-controlled trial was conducted with N = 316 young-women (M age = 20.80 years) across Australia and New Zealand. Media Smart-Targeted (MS-T) was a 9-module program released weekly while control participants received positive body image tips. Prevention effects (asymptomatic at baseline) and treatment effects (symptomatic at baseline) were investigated. MS-T participants were 94% and 91% less likely than controls to develop Moderate or higher depressive symptoms at 6-month (MS-T = 3.3%; controls = 35.4%) and 12-month follow-up (MS-T = 3.4%; controls = 29.4%), respectively. MS-T participants did not commence using recreational drugs at any assessment point, compared to 18.2% of controls at a least one assessment point. Regarding treatment effects, MS-T participants were 84% more likely to no longer be using recreational drugs at 12-month follow-up (MS-T = 60%; controls = 21.1%). Mutitvariate logistic regressions revealed group, depressive symptoms and alcohol use to be significant predictors of elevated suicide risk, where being an MS-T participant, without depressive symptoms and not drinking alcohol, significantly lowered likelihood of developing elevated suicide risk. Disordered eating at post-program mediated the relationship between group and depressive symptoms across post-program to 12-mnoth follow-up. MS-T shows promise as a program with important mental health benefits in addition to previous reports of lowered eating disorder diagnosis, risk and impairment.


Switching clozapine responders to olanzapine.
Clozapine is an atypical antipsychotic indicated for the management of severely ill patients with schizophrenia who have failed to respond adequately to standard drug treatment. The significant risk of agranulocytosis and seizure associated with clozapine has led to the restrictions in its use. Additionally, drug-induced sedation, sialorrhea, enuresis, and weight gain are often cited as problematic consequences of clozapine treatment. Our primary objective was to determine the effectiveness and safety of a method of slow cross-titration from clozapine to olanzapine among patients responsive to clozapine treatment but experiencing medication-induced adverse events. Changes in symptomatology, mood, subjective response, and safety were examined in 20 outpatients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder who converted from clozapine to olanzapine. Patients were considered clozapine-responsive as evidenced by improved social function and decreased symptoms with clozapine therapy; however, they were interested in alternative pharmacologic treatment because of clozapine-related side effects. Equivalent efficacy of olanzapine to clozapine was found in 90% of the patients (18/20) in the study group, without rehospitalization or suicidal behavior in any of the patients. Also notable was a reduction in drug-induced side effects and improved subjective response to pharmacotherapy. The successful conversion from clozapine to olanzapine has the potential to provide great benefits for the patient, including reducing drug-induced side effects while maintaining symptom control. These preliminary results suggest that further research on converting clozapine responders to olanzapine is warranted.


Lasting biological effects of early environmental influences. V. Viability, growth, and longevity.
The effects of neonatal influences on the growth and longevity of mice were studied by using animals derived from a highly inbred germfree colony that had been reassociated with a microbial flora free of known pathogens. The size of the animals at weaning time could be conditioned predictably by manipulating the diet of their mothers during gestation and lactation or by shortening or lengthening the period of lactation. A deficient diet during gestation or during lactation decreased the metabolic efficiency of the adult animal, even if it was fed an optimum diet after weaning. The effect was greatest when malnutrition occurred during both pregnancy and lactation. In contrast, an optimum diet during gestation and lactation rendered the animal less susceptible to the depressing effects of nutritional deficiency during adult life. A marked and lasting growth depression could be reproducibly achieved by contaminating newborn mice orally with an unidentified enterovirus. But neonatal infection with enterobacteria or mycobacteria even though severe, did not significantly alter the growth rate. Regardless of its initial cause, the depression of the growth rate during the preweaning period persisted throughout the whole life span of the animals, even when they were placed under optimum sanitary and nutritional conditions after weaning. Agencies (nutritional or infectious) which brought about a depression of whole body weight also affected the absolute and relative sizes of the various organs, especially of the brain. By manipulating neonatal influences, it was possible to produce at will in a given colony of highly inbred mice a family of strikingly different growth curves. This could be done without causing the death of any animal or affecting longevity.


Prevalence and incidence of venous leg ulcers-a protocol for a systematic review.
Venous leg ulcers (VLUs) are chronic wounds characterized by slow healing and high recurrence. Information on prevalence and incidence is essential for ascertaining the burden of VLU on the health care system and to inform epidemiological research, priority setting, and health care planning. The objective of this protocol is to present a transparent process for how we plan to review the existing international literature on the prevalence and incidence of VLU as well as the characteristics of the population reported within these studies. An exploratory search was performed using MEDLINE via PubMed and CINHAL via Ebsco to identify concepts, keywords, MeSH terms, and headings to identify study types looking at data of VLU prevalence and/or incidence and related patient characteristics. The findings of this exploratory search will determine the final search strategy. The titles and abstracts of the identified articles will be screened independently be two authors for relevance. Study which pass the quality assessment will be included. Data extraction will be performed independently by two authors and in accordance with a pre-designed data extraction form. If the data allows, a meta-analysis will be performed otherwise a descriptive summary of the findings will be conducted. The results of this review will contribute to the evidence base on VLU occurrence and may inform the decision making of healthcare professionals, policy-makers, and consumers. It will also inform future research in this area of VLU care. PROSPERO CRD42020205855.


Controlling cholera in the Ouest Department of Haiti using oral vaccines.
Following the 2010 cholera outbreak in Haiti, a plan was initiated to provide massive improvements to the sanitation and drinking water infrastructure in order to eliminate cholera from the island of Hispaniola by 2023. Six years and a half billion dollars later, there is little evidence that any substantial improvements have been implemented; with increasing evidence that cholera has become endemic. Thus, it is time to explore strategies to control cholera in Haiti using oral cholera vaccines (OCVs). The potential effects of mass administration of OCVs on cholera transmission were assessed using dynamic compartment models fit to cholera incidence data from the Ouest Department of Haiti. The results indicated that interventions using an OCV that was 60% effective could have eliminated cholera transmission by August 2012 if started five weeks after the initial outbreak. A range of analyses on the ability of OCV interventions started January 1, 2017 to eliminate cholera transmission by 2023 were performed by considering different combinations of vaccine efficacies, vaccine administration rates, and durations of protective immunity. With an average of 50 weeks for the waiting time to vaccination and an average duration of three years for the vaccine-induced immunity, all campaigns that used an OCV with a vaccine efficacy of at least 60% successfully eliminated cholera transmission by 2023. The results of this study suggest that even with a relatively wide range of vaccine efficacies, administration rates, and durations of protective immunity, future epidemics could be controlled at a relatively low cost using mass administration of OCVs in Haiti.


Gestational Diabetes Mellitus (GDM) - Diagnosis, Treatment and Follow-Up. Guideline of the DDG and DGGG (S3 Level, AWMF Registry Number 057/008, February 2018).
A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.