Clinician Engagement in Quality: A Literature Review.
Defining quality in the health care context has proven difficult, with many organizations not able to clearly articulate their use of this term in a manner that is easily understood by their clinical staff. This review seeks to investigate the literature to explore clinician engagement in quality including where engagement has been problematic, and if the reasons for this have been identified. An integrative review of the literature was undertaken to determine whether evidence within the literature supports a hypothesis that there is a lack of understanding of and engagement in quality at an organizational level by health professionals. A search of the literature was conducted using EBSCO Academic Complete, CINAHL, and MEDLINE databases. This article identified 18 studies where the understanding of quality by clinicians and their level of engagement with the process are investigated. We found that there has been no comprehensive study that explores the development of an agreed-upon definition and measurement of quality or clinician understanding and engagement in quality. The studies conducted have been small and discipline-specific. There is a growing body of evidence indicating that clinical and nonclinical staff interpret the meaning of quality and quality improvement differently. Quality and quality improvement are interpreted in relation to the clinician's individual work, professional, and learning and development experience. The literature suggests that clinician interpretation is influenced in part by their own personal beliefs and values, in addition to their interpretation of their individual work/professional responsibilities.


Identification of key mutations in HIV reverse transcriptase gene can influence the clinical outcome of HAART.
Therapeutic failures due to in vivo loss of drug sensitivity are still a major problem in AIDS care. Currently, the role of and methods for detecting resistant mutant strains in patients before therapeutic choices are still under debate. To investigate the relevance of screening for key mutations alone the commercial INNO-LiPA HIV-1 RT method was applied retrospectively to analyzing several HIV codons correlated with resistance to RTI (reverse-transcriptase inhibitors) in sera from 62 patients before starting HAART protocols, selected on the basis of clinical parameters. INNO-LiPA detected several resistant mutant strains, which were strictly consistent with previous selective pressure in the patients. A significant correlation between genotype pattern and response to HAART was found. The presence of key mutations associated with resistance to one or two RTI included in the protocol correlated with a decrease in treatment benefits, whereas patients with wild-type or non-resistant viral strains exhibited better response to HAART. Even if this information had been available when treatment was started, 45 of the patients would not have received different treatment. When compared with the total number of patients, the subgroup receiving a treatment that was considered retrospectively as consistent with the key mutation pattern exhibited a significantly better outcome. Although the interpretation of resistance-related key mutations needs improvement, this surrogate LiPA method seems to maintain a predictive role in the management of HIV infection, and is less expensive.


Report on the Na+/H+ Exchanger Satellite Meeting at the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology.
The Satellite Meeting on Na+/H+ Exchangers, held on 17 April 2010, covered a range of new developments in this field. The symposium was chaired by Dr. Larry Fliegel, University of Alberta, and the speakers were Dr. John Orlowski of McGill University, Dr. Jan Rainey of Dalhousie University, Dr. Etana Padan of The Hebrew University of Jerusalem, Dr. Masa Numata of The University of British Columbia, Dr. Pavel Dibrov from the University of Manitoba, Dr. Todd Alexander of the University of Alberta, and Grant Kemp of the University of Alberta. Talks ranged from organellar pH homeostasis to structure and function of Na+/H+ exchanger proteins. Highlights of the symposium included elucidation of the structure of transmembrane regions of the NHE1 isoform and development of a new model of the NHE1 protein based on the E. coli Na+/H+ exchanger. The symposium brought together scientists from different corners of the world. The discussions that followed were lively and many scientists received constructive comments from their peers.


Database "SIGMA Pro" information system and bibliographical management of active substances of plant protection products and biocides.
In order to satisfy its obligations as stipulated in European legislative, in 1998, the Management of Surface Waters in the Walloon Region modified its monitoring of plant protection products in surface waters in co-operation with the Regional Phyto Committee (LLN). Notably, this monitoring network takes into account the agricultural specifics of the main watersheds in Wallonia. It has led to the publication of a specific decree (A.G.W. of June 29th, 2000), which, among others, specifies the list of dangerous relevant substances in Walloon Region as well as their investigation methods (quality, monitoring network, action programmes). Together with the implementation of Directive 76/464/EEC concerning the pollution caused by some dangerous substances in aquatic environment, the Management of Surface Waters is also finalizing a database connected with plant production products. It contains technical data on active ingredients and relevant metabolites (nomenclature, toxicology, physico-chemical properties, ...), bibliographical information referring to these (synthesis of documents, table with results, ...) and some Internet connections. It has been elaborated so as to help Walloon public authorities make their decision.


Solution structure and behaviour of the Arabidopsis thaliana HYL1 protein.
In plants, microRNA biogenesis involves the complex assembly of molecular processes that are mostly governed by three proteins: RNase III protein DCL1 and two RNA binding proteins, SERRATE and HYL1. HYL1 protein is a double stranded RNA binding protein that is needed for the precise excision of miRNA/miRNA* duplex from the stem-loop containing primary miRNA gene transcripts. Moreover, HYL1 protein partners with HSP90 and CARP9 proteins to load the miRNA molecules onto the AGO1 endonuclease. HYL1 protein as a crucial player in the biogenesis pathway is regulated by its phosphorylation status to fine tune the levels of miRNA in various physiological conditions. HYL1 protein consists of two dsRNA binding domains (dsRBD) that are involved in RNA binding and dimerization and a C-terminal disordered tail of unknown function. Although the spatial structures of the individual dsRBDs have been determined there is a lack of information about the behaviour and structure of the full length protein. Using small the angle X-ray scattering (SAXS) technique we investigated the structure and dynamic of the HYL1 protein from Arabidopsis thaliana in solution. We show that the C-terminal domain is disordered and dynamic in solution and that HYL1 protein dimerization is dependent on the concentration. HYL1 protein lacking a C-terminal tail and a nuclear localisation signal (NLS) fragment is almost exclusively monomeric and similarly to full-length protein has a dynamic nature in solution. Our results point for the first time to the role of the C-terminal fragment in stabilisation of HYL1 dimer formation.


Some evidence for interaction of D-cycloserine with DNA.
D-Cycloserine showed a decreased lethality against paraquat-treated E. coli than against non-treated cells. E. coli K12 mutants which were deficient in DNA repair were more sensitive than the wild type strain to D-cycloserine. Furthermore, D-cycloserine caused PM2 DNA cleavage in the presence of Fe2+, and the cleavage was strongly inhibited by singlet oxygen scavengers. These results indicate that D-cycloserine interacts with DNA and an active oxygen species is involved in the interaction.


Immunohistochemical localization and physiological regulation of carbonyl reductase in immature rat ovary.
The present study was performed to clarify the role of the ovarian carbonyl reductase (OCR) in ovarian function in immature rats. The OCR activities towards three specific substrates, 13,14-dihydro-PGF2 alpha, 4-benzoylpyridine and menadione, were photometrically and radiochemically determined in the 9,000 x g supernatants of ovaries, and OCR content was measured by Western-blot-peroxidase anti-peroxidase (PAP) analysis. Immunohistochemical localization of the enzyme in the ovary was performed by the avidin-biotin-complex (ABC) method for paraffin sections. Positive immunoreactivity with OCR antibody was observed for the theca cells and interstitial gland cells at 72 hr after pregnant mare serum gonadotropin (PMSG) treatment when ovulation was confirmed, and the granulosa cells were consistently negatively stained. The OCR activity was significantly increased by PMSG, human chorionic gonadotropin (hCG) and PMSG-hCG treatments, but estradiol and tamoxifen overcame the effect of PMSG on the enzyme activity. Moreover, estradiol enhanced the effect of hCG, but tamoxifen did not. Changes in the OCR activity well-correlated with those in the OCR content. These findings indicate that the OCR is regulated by gonadotropin and estrogen and that metabolites formed by the enzyme could be closely involved in ovarian cell function.


General-purpose infusion pumps. Evaluating the B. Braun Outlook Safety Infusion System.
General-purpose infusion pumps deliver liquid medications and intravenous (i.v.) fluids to patients through i.v. or epidural routes at specified flows. They are most often used when greater accuracy or higher flows are needed than can be provided by a manually adjusted gravity administration set. In this Evaluation (which updates our October 2002 study), we present our findings for two newly evaluated pumps: the B. Braun Outlook 100 and Outlook 200. The Outlook 200 is the first general-purpose infusion pump to offer a new type of safety feature: an automated programming system. This system scans bar-coded labels on i.v. fluid containers and on patient (and sometimes clinician) identification and automatically programs this information into the pump. Unfortunately, the 200's system has not yet been successfully implemented in a clinical setting.


Isotopic pattern and accurate mass determination in urine drug screening by liquid chromatography/time-of-flight mass spectrometry.
An efficient method was developed for toxicological drug screening in urine by liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry. The method relies on a large target database of exact monoisotopic masses representing the elemental formulae of reference drugs and their metabolites. Mass spectral identification is based on matching measured accurate mass and isotopic pattern (SigmaFit) of a sample component with those in the database. Data post-processing software was developed for automated reporting of findings in an easily interpretable form. The mean and median of SigmaFit for true-positive findings were 0.0066 and 0.0051, respectively. The mean and median of mass error absolute values for true-positive findings were 2.51 and 2.17 ppm, respectively, corresponding to 0.65 and 0.60 mTh. For routine screening practice, a SigmaFit tolerance of 0.03 and a mass tolerance of 10 ppm were chosen. Ion abundance differences from urine extracts did not affect the accuracy of the automatically acquired SigmaFit or mass values. The results show that isotopic pattern matching by SigmaFit is a powerful means of identification in addition to accurate mass measurement.


Subtalar joint coalition in children: new observations.
Eleven children with clinical and radiographic findings suggestive of nonosseous subtalar coalition were found to have fibrous bridges at the time of surgery. A second group of 14 children with similar clinical and radiographic findings is being conservatively treated at present. This series of children suggests that a common site of nonosseous subtalar coalition is found posterior to the sustentaculum tali. Diagnosis of nonosseous coalition requires careful examination with computed tomography, with attention to subtle changes in the hindfoot, particularly posterior to the sustentaculum tali.


Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people.
To investigate the relation between cannabis use and psychotic symptoms in individuals with above average predisposition for psychosis who first used cannabis during adolescence. Analysis of prospective data from a population based sample. Assessment of substance use, predisposition for psychosis, and psychotic symptoms was based on standardised personal interviews at baseline and at follow up four years later. 2437 young people (aged 14 to 24 years) with and without predisposition for psychosis. Psychotic symptoms at follow up as a function of cannabis use and predisposition for psychosis at baseline. After adjustment for age, sex, socioeconomic status, urbanicity, childhood trauma, predisposition for psychosis at baseline, and use of other drugs, tobacco, and alcohol, cannabis use at baseline increased the cumulative incidence of psychotic symptoms at follow up four years later (adjusted odds ratio 1.67, 95% confidence interval 1.13 to 2.46). The effect of cannabis use was much stronger in those with any predisposition for psychosis at baseline (23.8% adjusted difference in risk, 95% confidence interval 7.9 to 39.7, P = 0.003) than in those without (5.6%, 0.4 to 10.8, P = 0.033). The risk difference in the "predisposition" group was significantly greater than the risk difference in the "no predisposition" group (test for interaction 18.2%, 1.6 to 34.8, P = 0.032). There was a dose-response relation with increasing frequency of cannabis use. Predisposition for psychosis at baseline did not significantly predict cannabis use four years later (adjusted odds ratio 1.42, 95% confidence interval 0.88 to 2.31). Cannabis use moderately increases the risk of psychotic symptoms in young people but has a much stronger effect in those with evidence of predisposition for psychosis.


Detection of HBs-Ag in the pancreas in cases of pancreatic carcinoma.
Detection of HBs-Ag in the pancreatic juice in acute and chronic hepatic failure caused by hepatitis-B-infection leads to the assumption that parts of that virus are produced by the pancreas. We investigated pancreatic tissue obtained during Whipple's procedure in 51 cases of pancreatic carcinoma. In 5 specimens HBs-Ag was detected, mostly located in acinar cells and inside small ducts. In view of our knowledge of the carcinogenesis of human hepatocellular carcinoma, hepatitis B virus could produce an oncogenic effect in pancreatic carcinoma, too.


Targeting screening mammography according to life expectancy among women undergoing dialysis.
Screening guidelines recommend that mammography be targeted to women likely to live longer than 5 years. Because women undergoing dialysis have a reduced but variable life expectancy, their appropriate use of screening is controversial. Therefore, we conducted this study to describe national mammography rates among women undergoing dialysis with differing prognostic factors and to determine whether screening is targeted to healthier women who live longer. Using the US Renal Data System, we identified 17,090 women aged 50 years or older who started dialysis in 1997. We tracked women for 5 years to ascertain their use of screening mammography or death. The 5-year survival rate was 25%. The biennial screening mammography rate was 25%, ranging from 12% for women aged 80 years or older to 69% for women who were ever on the transplant list. Women who were screened in the past year had a lower death rate than those who were not (hazards ratio, 0.55; 95% confidence interval, 0.51-0.59). Yet, 2198 women (13%) who died within 5 years underwent screening, and 2004 women (12%) who lived more than 5 years while receiving dialysis did not undergo screening. Screening mammography rates are appropriately low among women undergoing dialysis because the 5-year survival rate is low. Screening is being targeted to women who are healthier and live longer. However, targeting could be improved by increasing screening in the few women undergoing dialysis with substantial life expectancies while decreasing screening in most women undergoing dialysis who live less than 5 years.


[Diabetes in the Belgian province of Luxembourg: frequency, importance of the oral glucose tolerance test and a modestly increased fasting blood glucose].
A sample of 1949 subjects aged 35-64 years has been studied in the Belgian Province of Luxembourg according with the MONICA project (MONItoring of Trends and Determinants in CArdiovascular Diseases) elaborated by the World Health Organization. Among the data collected, were a fasting glycaemia and a glycaemia at the second hour of a 75 grams oral glucose load. Analysis of these two parameters has allowed to divide the individuals of the study into: 4.1% of diabetic subjects which half of them being unknown, 5.2% of subjects presenting an impaired glucose tolerance, 3.4% of subjects with an early reactive hypoglycaemia and 87.3% of normoglycaemic subjects. The measurement of the fasting glycaemia alone has allowed to display 15 glucidic abnormalities (that is to say 0.8%) whereas the complementary realization of the oral glucose tolerance test has disclosed about 10% of additional abnormalities. The fact to consider a borderline fasting glycaemia (included between 110 and 140 mg/dl on venous plasma) result in a greater probability to find an abnormal blood glucose value at the second hour of the oral glucose tolerance test.


A phenotype based approach for the immune monitoring of NY-ESO-1-specific CD4+ T cell responses in cancer patients.
Because of its frequent expression in tumors and spontaneous immunogenicity in advanced cancer patients, NY-ESO-1 is presently viewed as a prototype tumor antigen for the development of cancer vaccines. A prerequisite for the analysis of NY-ESO-1-specific T cell responses in vaccinated patients is the assessment of the complete T cell repertoire available for the antigen. Here, we have assessed frequency and fine specificity of CD4+ T cells reactive against NY-ESO-1-derived sequences in circulating lymphocytes from cancer patients with spontaneous responses to the antigen. We found that, relative to healthy donors, this frequency was only moderately increased in cancer patients. The reactivity of these cells, however, was directed against the same immunodominant regions previously identified for healthy donors. On account of these data, we developed an approach for the immune monitoring of NY-ESO-1-specific CD4+ T cell responses based on the assessment of CD4+ T cell populations of defined phenotype. Using this approach, a similar frequency of NY-ESO-1-specific CD4+ T cells was found among naive T cells of healthy donors and cancer patients. In contrast, among antigen-experienced T cells, NY-ESO-1-specific CD4+ T cells were exclusively detectable in cancer patients. We anticipate that this phenotype-based approach will be useful for the immune monitoring of vaccine-induced responses in vaccination trials using NY-ESO-1 as well as other tumor antigens.


[Development of plasmid DNA-based gene transfer].
Gene therapy based on ultrasound with microbubbles offers a novel approach for the prevention and treatment of variety of diseases. The major development of gene transfer has importantly contributed to intense investigation of the potential of gene therapy in cancer or cardiovascular medicine. The amazing advances in molecular biology have provided a dramatic improvement of the technology that is necessary to transfer target genes into somatic cells. Gene transfer methods have been surprisingly improved. In fact, some of them (retroviral vectors, adenoviral vectors or liposome based vectors, etc.) have been used in the clinical trials already. But some severe side effects were reported in clinical gene therapy using such viral, so people desire safe and efficient clinical gene therapy. Recently, ultrasound-mediated gene transfer has been reported to augment the transfection efficiency and facilitate local gene expression. Interestingly, gene transfer into the fetal central nervous system was successfully achieved by intrauterine injection with microbubble-enhanced ultrasound. Compared to other viral vectors, there are some theoretical advantages including safety, simplicity of preparation, and local gene transfer. Thus, we focused on the development of gene transfer using naked plasmid DNA with an ultrasound or microbubble-enhanced ultrasound method.


Chemical synthesis and biological activity of the neopetrosiamides and their analogues: revision of disulfide bond connectivity.
Neopetrosiamides A and B (2) from the marine sponge Neopetrosia sp. are two diastereomeric tricyclic peptides that inhibit tumor cell invasion associated with metastasis. The reported structures were chemically synthesized using solid-phase peptide synthesis and sequential stepwise disulfide bond formation in solution. The disulfide bond connectivity of the originally proposed structures was revised and confirmed by chemical synthesis together with a combination of HPLC analysis, disulfide mapping, and biological activity testing. This methodology was also utilized to generate analogues containing methionine or norleucine in place of the methionine sulfoxide at position 24. Compounds 4 and 6 demonstrated potent bioactivity comparable to that of the parent peptides.


Human immunodeficiency virus (HIV) infection and the kidney.
Since the first report on the acquired immunodeficiency syndrome (AIDS) in 1981, organ involvement of AIDS has increased. We discuss the effect of human immunodeficiency virus (HIV) infection, the causative agent of AIDS, on the field of nephrology. Hyponatremia, the commonest fluid and electrolyte abnormality, is caused by various pathophysiologic mechanisms, including adrenal insufficiency. The renal parenchymal complications are diverse, but a new entity, HIV-associated nephropathy, is becoming recognized because of its characteristic clinical and pathologic features, including the fact that it causes irreversible renal failure. HIV infection in patients with end-stage renal failure, both before and after initiation of maintenance dialysis, is a significant problem. The present methods of preventing spread of virus in dialysis units seem successful. Few patients who are infected with HIV or who have AIDS have had renal transplantation, although unsuspected viral infection of cadaveric organs remains a concern.


Motivational interviewing in musculoskeletal care.
Motivational interviewing is a patient-centred counselling method designed to build motivation for behaviour change by resolving ambivalence. It was developed in the addictions field and has since been applied to medical and health promotion settings. This paper will provide a brief overview of the method and will discuss how it may be used in consultations for patients with musculoskeletal problems to increase engagement with treatment and to build motivation for helpful behaviour change.


Collagen vascular grafts: a step towards improved compliance in small-calibre bypass surgery; preliminary report.
This study assesses the static compliance of a 4-mm-calibre collagen vascular graft. The graft was prepared by extrusion from a gel of collagen obtained from the skin of grown calves. To allow easy surgical handling, the prosthesis was reinforced by embedding a polyester mesh between two concentric tubes of collagen. Compliance was determined in vitro by filling the graft with increasing volumes of saline while intraluminal pressure and longitudinal stretching were simultaneously recorded. A 4-mm polytetrafluoroethylene prosthesis and a freshly-harvested human saphenous vein served as references. In the range of physiological pressures (100 to 200 mmHg), the collagen graft was only half as stiff as the polytetrafluoroethylene graft (5.6 vs 2.7 mm3/mb/m) and, in spite of its reinforcement, yet slightly more compliant than the vein itself (4.5 mm3/mb/m). Thus, from a mechanical viewpoint, a collagen prosthesis seems to be a valuable alternative for small-vessel bypass grafting, but further studies of its flow-surface characteristics are now warranted to assess its potential usefulness in the clinical setting.


Disintegrants combination: development and optimization of a cefadroxil fast disintegrating tablet.
Fast Disintegrating Tablets (FDTs) is a rapidly growing dosage form preferred for special population (pediatric, geriatric and psychotic patients). It is also developed with the aim of improving bioavailability and patient compliance. During the present study, cefadroxil fast disintegrating tablets formulations (n=9) were designed and optimized by central composite design with two independent variables (croscarmellose and crospovidone) using design expert® software. The effects of independent variables on formulation properties such as friability, hardness, in vitro dispersion and disintegration were assessed by drawing response surface graphs with design expert® software. Tablets were assessed for pharmacopeial and non-pharmacopeial parameters to ensure the quality of compressed tablets. Among all formulations, F3, F8 and F9 have shown better results. The formulation F9 containing 15mg croscarmellose and 33.075mg crospovidone showed good pharmacotechnical attributes as well as shelf life. F 9 showed improved dissolution with t90% of> 2 min and will lead to better bioavailability.


[Role of pentoxifylline retard dosage forms in the correction of hemodynamic disorders in retinal venous occlusion and diabetic retinopathy].
The investigation was undertaken to study the effect of the pentoxifylline retard dosage form Vasonit on ocular hemodynamics in patients with retinal vein occlusions and non-proliferative diabetic retinopathy (DR). Forty-two patients aged 45 to 75 years, including 20 patients (20 eyes) with retinal vein occlusion in the presence of hypertensive disease and atherosclerosis (Group 1) and 22 patients (44 years) with non-proliferative DR (Group 2), were examined. All the patients received the pentoxifylline retard dosage form Vasonit, 600 mg twice a day, for 2 months. After a course of pentoxifylline therapy, the patients were observed to have improved visual functions, positive clinical changes in the fundus of the eye as a reduction in the frequency and extent of retinal hemorrhages, in the degree of manifestations of macular edema, in the number of retinal microaneurysms and ischemic areas. The results of color Doppler mapping of ocular and orbital vessels are indicative of improved hemodynamics as an increase in the values of blood flow velocity and normalization of blood flow resistance and pulsation indices in the arteries supplying blood to the retina and optic nerve.


Usefulness of glycated hemoglobin as diagnostic criteria for metabolic syndrome.
The metabolic syndrome (MetS) is the clustering of cardiovascular risk factors and known as a powerful predictor of diabetes and cardiovascular disease. Glycated hemoglobin (HbA1c) is used as one of the diagnostic criteria for diabetes and category of increased risk for diabetes. We examined the usefulness of HbA1c as a diagnostic tool for MetS and to determine the cut-off value of HbA1c as a criterion for MetS, in non-diabetic Korean subjects. We analyzed 7,307 participants (male: 4,181, 57%) in a medical check-up program, and applied the newly recommended guidelines of the International Diabetes Federation for diagnosis of MetS. The mean HbA1c was 5.54% in all subjects and showed no significant difference between genders. Using receiver-operating characteristic curve, HbA1c value corresponding to the fasting plasma glucose value of 100 mg/dL was 5.65% (sensitivity 52.3%, specificity 76.7%). The prevalence of MetS was 8.5% according to the IDF guideline and 10.9% according to HbA1c value of 5.7%, showing 69.5% agreement rate. The detection rate of MetS increased to 25.7% using the HbA1c criterion of 5.7% instead of fasting hyperglycemia. This study suggests that HbA1c might be used as a diagnostic criterion for MetS and the appropriate cut-off value of HbA1c may be 5.65% in this Korean population.


Alcoholic cardiomyopathy: a review.
Alcohol abuse can cause cardiomyopathy indistinguishable from other types of dilated nonischemic cardiomyopathy. Most heavy drinkers remain asymptomatic in the earlier stages of disease progression, and many never develop the familiar clinical manifestations that typify heart failure. We review the current thinking on the pathophysiology, clinical characteristics, and treatments available for alcoholic cardiomyopathy. The relationship of alcohol to heart disease is complicated by the fact that in moderation, alcohol has been shown to afford a certain degree of protection against cardiovascular disease.


EvidenceNOW: Balancing Primary Care Implementation and Implementation Research.
The mission of the Agency for Healthcare Research and Quality (AHRQ) is to generate knowledge about how America's health care delivery system can provide high-quality care, and to ensure that health care professionals and systems understand and use this evidence. In 2015 AHRQ invested in the largest primary care research project in its history. EvidenceNOW is a $112 million effort to disseminate and implement patient-centered outcomes research evidence in more than 1,500 primary care practices and to study how quality-improvement support can build the capacity of primary care practices to understand and apply evidence.EvidenceNOW comprises 7 implementation research grants, each funded to provide external quality-improvement support to primary care practices to implement evidence-based cardiovascular care and to conduct rigorous internal evaluations of their work. An independent, external evaluator was funded to conduct an overarching evaluation using harmonized outcome measures and pooled data. The design of EvidenceNOW required resolving tensions between implementation and implementation research goals.EvidenceNOW is poised to develop a blueprint for how stakeholders can invest in strengthening the primary care delivery system and to offer a variety of resources and tools to improve the capacity of primary care to deliver evidence-based care. Federal agencies must maximize the value of research investments to show improvements in the lives and health of Americans and the timeliness of research results. Understanding the process and decisions of a federal agency in designing a large clinical practice transformation initiative may provide researchers, policy makers, and clinicians with insights into future implementation research, as well as improve responsiveness to funding announcements and the implementation of evidence in routine clinical care.


National data for monitoring and evaluating racial and ethnic health inequities: where do we go from here?
The elimination of racial and ethnic health inequities has become a central focus of health education and the national health agenda. The documentation of an increasing gap in life expectancy and other health outcomes suggests the need for more effective strategies to eliminate health inequities, which can be informed by better monitoring and evaluation data. Although the sophistication and volume of health data available have increased dramatically in recent years, this article examines the quality of the current data collected to achieve the goal of eliminating racial and ethnic health inequities. This article explores several key aspects of data to inform addressing inequities including terminology, the role of data, and explanations of the problem. The authors conclude with recommendations for refining data collection to facilitate the elimination of racial and ethnic health inequities and suggest how the Society for Public Health Education can become a more central figure in our national efforts.


Dielectric relaxation studies and dissolution behavior of amorphous verapamil hydrochloride.
Verapamil hydrochloride (VH) is a very popular calcium channel blocker. Solubility of its crystalline form in the blood reaches only 10-20%. Thus, it seems to be very important to improve its bioavailability. In this article, we show that the preparation of the amorphous form of VH enhance its dissolution rate. In addition we performed dielectric measurements to describe molecular dynamics of this active pharmaceutical ingredient (API). Since examined sample is typical ionically conducting material, to gain information about structural relaxation we employed the dielectric modulus formalism. The temperature dependence of the structural relaxation time can be described over the entire measured range by a single Vogel-Fulcher-Tamman (VFT) equation. From the VFT fits the glass transition temperature was estimated as T(g) = 320.1 K. Below glass transition temperature one clearly visible secondary relaxation, with activation energy E(a) = 37.8 kJ/mol, was reported. Deviations of experimental data from KWW fits on high-frequency flank of alpha-peak indicate the presence of an excess wing in tested sample. Based on Kia Ngai's coupling model we identified the excess wing as true Johari-Goldstein process.


Pharmacological and environmental factors in primary angle-closure glaucoma.
A large number of drug classes have now been reported to provoke angle closure in high-risk individuals. The mechanism of action can be generalized into three main categories: sympathomimetic, parasympatholytic and idiosyndratic reactions. This review of the ophthalmic literature provides a clinical summary of primary angle-closure glaucoma (PACG) and its management. External stimuli (pharmacological and environmental) may induce acute, and more often, asymptomatic angle closure, which carries a significant risk of glaucoma. Whenever in doubt, patients at risk of PACG who are starting on drug therapy known to provoke angle closure or aggravate the condition should be referred for detailed gonioscopic examination of the anterior chamber by an ophthalmologist. AREAS FOR DEVELOPING RESEARCH: The use of new imaging methods such as anterior segment optical coherence tomography to assess the presence or risk of angle closure is gaining popularity, and may offer a more rapid method of identifying people who are at risk of sight loss from angle-closure glaucoma precipitated by non-ophthalmological medication.


The effect of music on anxiety in women undergoing cesarean delivery: a systematic review and meta-analysis.
This study aimed to evaluate the effect of music on anxiety in patients undergoing cesarean delivery. An electronic search of PubMed, CINAHL, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials was performed from inception to November 2020. Eligibility criteria included all randomized controlled trials of pregnant women undergoing cesarean delivery who were randomized to either the music intervention or control. Studies needed to measure preoperative, intraoperative, or postoperative anxiety via a visual analog scale, State-Trait Anxiety Inventory, or Zung Self-Rating Anxiety Scale, for inclusion. The primary outcome was intraoperative anxiety during cesarean delivery. Secondary outcomes included preoperative and postoperative anxiety, postoperative pain, postoperative opioid requirements, blood pressure, and heart rate. The methodologic quality of the included studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce a summary of treatment effects in terms of mean difference with 95% confidence intervals. A prespecified subgroup analysis of patients undergoing a scheduled or an unscheduled cesarean delivery was carried out for the main outcomes. Of the 1296 studies screened, 15 met the inclusion criteria (n=613 music group vs n=748 controls). Three trials (n=217 music group vs n=215 controls) reported on intraoperative anxiety specifically. Among studies using a visual analog scale for anxiety assessment, women in the intervention group had lower intraoperative anxiety levels than the controls (mean difference, -0.54; 95% confidence interval, -0.87 to -0.20; I2=0%; n=2 studies). One trial used the State-Trait Anxiety Inventory and 1 trial used the Zung Self-Rating Anxiety Scale for intraoperative anxiety assessment. In both of these studies, music exposure was associated with lower anxiety levels when compared with the controls (State-Trait Anxiety Inventory: mean difference, -2.80; 95% confidence interval, -4.57 to -1.03; Zung Self-Rating Anxiety Scale: mean difference, -4.80; 95% confidence interval, -7.08 to -2.52). In the subgroup analyses, the same relationship persisted when the cesarean delivery was unscheduled and when the music was selected by the patient or by the study team. The effect of music on preoperative and postoperative anxiety varied depending on which anxiety assessment tool was used. Music was also associated with decreased opioid use (mean difference, -0.87; 95% confidence interval, -1.55 to -0.19; I2=0%). In patients undergoing a cesarean delivery, music is associated with decreased intraoperative anxiety.


Promises and pitfalls of anti-angiogenic therapy in clinical trials.
A significant body of research has implicated the process of angiogenesis in the growth and spread of tumors. Elucidation of the mechanisms of tumor angiogenesis has led to the development of multiple anti-angiogenic agents. However, the perceived differences between the results of preclinical studies and those of early phases of clinical trials have led to questions being asked regarding the efficacy of these agents. There are many reasons for this discrepancy, including difficulties in the appropriate interpretation of preclinical data and clinical trial design. Further insights into the complex process of angiogenesis are essential for the development of effective anti-angiogenic regimens.


Spider senses - technical perfection and biology.
This essay deals with sensory biology in a broad sense. It takes mechanosensory systems of spiders to illustrate a few basic issues. Particular attention is given to two aspects. 1. There is a remarkable "ingenuity" in the uptake and transformation of the adequate stimuli way out in the sensory periphery, which is reflected by an intimate relationship between the physical properties of the stimuli and the characteristics of the structures receiving and transforming them. We need to understand the details of this relationship in order to understand the relationship of an organism to its environment. 2. Sensory systems represent interfaces between the environment and behavior. As highly selective filters they have not evolved to provide abstract knowledge but to guide a particular behavior. The signals sent to the central nervous system are meaningful only in regard to their behavioral significance. - Some details of stimulus transformation in biological strain gauges (slit sensilla), airflow detectors (trichobothria) and touch receptors (tactile hairs) are described. Some of the refinement in the periphery is then meshed with the behavior of the whole organism. In this way the value shall be underlined of trying to understand reductionist details as building blocks of the complexity which enables an organism to behave in its own particular way in its species specific environment.


Projecting the self outside the body: Body representations underlying proprioceptive imagery.
Recent research has shown that proprioception relies on distorted representations of body size and shape. By asking participants to localise multiple landmarks on their occluded hand, perceptual maps of hand size and shape can be constructed and compared to actual hand structure. These maps are different from the actual size and shape of the occluded hand, revealing underestimation of finger length and overestimation of hand width. Here we tested whether the same distorted body model underlies proprioceptive imagery (i.e. imagining the hand at a specific location, and in a different posture than it actually is). In Experiment 1, participants placed their left hand under an occluding board (real condition) or imagined their left hand under the board (imagined condition). Highly similar distortions were found in both conditions. Furthermore, results across the two conditions were strongly correlated. In Experiment 2, participants completed the real condition and two imagined conditions. In the imagined-fist condition, participants held their left hand in a fist, in their lap, while in the imagined-flat condition, participants held their left hand flat, with palm down, in their lap. In both imagined conditions, participants were asked to imagine their left hand lying flat, with palm down, under the occluding board. A similar pattern of distortions was found in all three conditions. These results suggest that both proprioception and proprioceptive imagery reply on a common stored model of the body's metric properties.


Two cases of interstitial deletion 1p.
We report two cases of interstitial deletion of the short arm of chromosome 1. The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2); the second was a 6 month old boy with a chromosome complement of 46,XY,del(1) (p22.3p31.3). A number of the malformations observed were common to both cases. There has been one previously reported case with the same breakpoints as our case 1 and a phenotype that was strikingly similar.


Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype.
Recent studies suggest that the human Abelson helper integration site-1 (AHI1) gene on chromosome 6 is associated with susceptibility to schizophrenia and autism, two common neuropsychological disorders with depression symptoms. Mouse Ahi1 protein is abundant in the hypothalamus and amygdala, which are important brain regions for controlling emotion. However, the neuronal function of Ahi1 remains unclear. With the Cre-loxP system, we created a mouse model that selectively reduces Ahi1 expression in neuronal cells. Mice with neuronal Ahi1 deficiency show reduced TrkB level in the brain and depressive phenotypes, which can be alleviated by antidepressant drugs or by overexpression of TrkB in the amygdala. Ahi1 deficiency promotes the degradation of endocytic TrkB and reduces TrkB signaling in neuronal cells. Our findings suggest that impaired endocytic sorting and increased degradation of TrkB can induce depression and that this impaired pathway may serve as a previously uncharacterized therapeutic target for depression.


Gastric Adenocarcinoma of the Fundic Gland Type: Update and Literature Review.
Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity with a lack of awareness amongst general surgical pathologists and this review highlights the key features and controversies associated with this uncommon neoplasm. A literature search through PubMed using synonyms for GA-FG was conducted to obtain 111 cases. GA-FG is a well-differentiated neoplasm of oxyntic mucosa, that is comprised of chief cells and parietal cells. Chief cell differentiation is highlighted with Muc-6, RUNX3, and pepsinogen. Parietal cells are highlighted with H+/K+ ATPase and PDGFRA-α. Association with Helicobacter infection, chronic gastritis, intestinal metaplasia, or gastric atrophy is not seen. Most GA-FGs are confined to the mucosa. Deeper invasion, lymphovascular invasion, nodal metastasis, and extragastric spread are uncommon. GA-FGs are rare lesions that typically follow a benign course. However, despite features of malignancy in some cases, complete surgical excision, sometimes with endoscopic mucosal resection, seems adequate treatment.


Gross cystic disease fluid protein-15 in salivary gland tumors.
Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.


High-Performance Organic Field-Effect Transistors Fabricated Based on a Novel Ternary π-Conjugated Copolymer.
In this study, we developed a ternary conjugated polymer, IFBT-TT, consisting of centrosymmetric indaceno[1,2-b:5,6-b']dithiophene and thieno[3,2-b]thiophene as the electron-donating units and an asymmetric 5-fluorobenzo[c][1,2,5]thiadiazole as the electron-accepting unit. The target copolymer was synthesized using an acceptor-donor-acceptor (A-D-A) type of macromonomer, which gave the target copolymer a precisely defined D1-A-D2-A architecture. Theoretical simulation revealed that the IFBT-TT features C-H···N and F···S nonbonding interactions, leading to a highly rigid and planar molecular backbone. Although the spin-cast IFBT-TT films exhibited an amorphous morphology lacking in ordered structures, the fabricated field-effect transistors presented remarkable p-type transport properties with high mobility of up to 5.0 cm2 V-1 s-1 and excellent ambient stability. These observations highlight that the integration of a three-component D1-A-D2-A-type backbone framework is an effective molecular design strategy for high-mobility conjugated polymers.


Host intrinsic determinants and potential consequences of parasite infection in free-ranging red-fronted lemurs (Eulemur fulvus rufus).
Parasites and infectious diseases represent ecological forces shaping animal social evolution. Although empirical studies supporting this link abound in various vertebrate orders, both the study of the dynamics and impact of parasite infections and infectious diseases in strepsirrhine primates have received little empirical attention. We conducted a longitudinal parasitological study on four groups of wild red-fronted lemurs (Eulemur fulvus rufus) at Kirindy Forest, Madagascar, during two field seasons in consecutive years to investigate i) the degree of gastrointestinal parasite infection on population and individual levels and ii) factors potentially determining individual infection risk. Using a comprehensive dataset with multiple individually assignable parasite samples as well as information on age, sex, group size, social rank, and endocrine status (fecal androgen and glucocorticoid), we examined parasite infection patterns and host traits that may affect individual infection risk. In addition, we examined whether parasite infection affects mating and reproductive success. Our results indicated high variability in parasite infection on individual and population levels. Time of year and group size was important determinants of variability in parasite infection. Variation in hormone levels was also associated with parasite species richness and parasite infection intensity. Differences in parasite infection between years indicate a potential immune-enhancing function of steroid hormones on nematode infections, which has not been reported before from other vertebrates studied under natural conditions. Male mating and reproductive success were not correlated to any measure of parasite infection, which suggests a nonfunctional role of the parasites we examined in primate sexual selection.


Core single nucleotide polymorphism analysis reveals transmission of Mycobacterium marinum between animal and environmental sources in two aquaria.
Mycobacterium marinum is a slow-growing, photochromogenic nontuberculous mycobacterium, which can cause mycobacteriosis in various animals, including humans. Several cases of fish mycobacteriosis have been reported to date. Mycobacterium marinum has also been isolated from aquatic environmental sources such as water, sand, biofilms, and plants in the natural environments. Hence, we hypothesized that a wide variety of sources could be involved in the transmission of M. marinum. In this study, we tested this hypothesis by isolating M. marinum from various sources such as fish, invertebrates, seagrass, periphytons, biofilms, sand, and/or water in two aquaria in Japan and conducting a phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) using whole-genome sequences of the isolated strains. The analysis revealed that the strains from animal and environmental sources belonged to the same clusters. This molecular-based study epidemiologically confirmed that various sources, including fish, invertebrates, and environmental sources, could be involved in transmission of M. marinum in a closed-rearing environment. This is the first report where M. marinum was isolated from different sources, and various transmission routes were confirmed in actual cases, which provided essential information to improve the epidemiology of M. marinum.


Patients colonized by antibiotic resistant bacteria--a potential source of infections in the medical wards.
Bacterial colonization was studied in 12 non-infected female patients admitted into one medical ward, Siriraj hospital, Bangkok, from March to June 1988. Swabs were taken on the first day of admission, then every other day until discharge, from six sites; i.e. anterior nares, vault of axilla, hands, anterior chest, abdomen and toe web. The times and total number of swabbing were 52 and 312 respectively. All patients were colonized with bacteria. S. epidermidis was found in all patients. S. aureus was found in 9 patients, 48 times (15.4%). Methicillin-resistant S. aureus (M.R.S.A.) was identified in 4 patients on 10 occasions (3.2%). Gram-negative bacilli were isolated in 11 of 12 patients, and the number of positive samples was 60 (19.2%). All bacteria were highly resistant to the commonly used antimicrobials. The study failed to show that colonization increased with the duration of hospitalization. It is concluded that the majority of patients who had been colonized with pathogenic bacteria were important sources of infections in the medical ward.


Polar/apolar interfaces modulate the conformational behavior of cyclic peptides with impact on their passive membrane permeability.
Cyclic peptides have the potential to vastly extend the scope of druggable proteins and lead to new therapeutics for currently untreatable diseases. However, cyclic peptides often suffer from poor bioavailability. To uncover design principles for permeable cyclic peptides, a promising strategy is to analyze the conformational dynamics of the peptides using molecular dynamics (MD) and Markov state models (MSMs). Previous MD studies have focused on the conformational dynamics in pure aqueous or apolar environments to rationalize membrane permeability. However, during the key steps of the permeation through the membrane, cyclic peptides are exposed to interfaces between polar and apolar regions. Recent studies revealed that these interfaces constitute the free energy minima of the permeation process. Thus, a deeper understanding of the behavior of cyclic peptides at polar/apolar interfaces is desired. Here, we investigate the conformational and kinetic behavior of cyclic decapeptides at a water/chloroform interface using unbiased MD simulations and MSMs. The distinct environments at the interface alter the conformational equilibrium as well as the interconversion kinetics of cyclic peptide conformations. For peptides with low population of the permeable conformation in aqueous solution, the polar/apolar interface facilitates the interconversion to the closed conformation, which is required for membrane permeation. Comparison to unbiased MD simulations with a POPC bilayer reveals that not only the conformations but also the orientations are relevant in a membrane system. These findings allow us to propose a permeability model that includes both 'prefolding' and 'non-prefolding' cyclic peptides - an extension that can lead to new design considerations for permeable cyclic peptides.


Temperature dependence of indigo light emission from mesoporous ZnO/porous silicon nanocomposites.
Nanocomposites of mesoporous zinc oxide (ZnO) and porous silicon (PS) were prepared through a hydrothermal method. Room-temperature (RT) and temperature-dependent photoluminescence (PL) were performed to investigate the optical properties and temperature dependence of the indigo emission peak from the ZnO/PS nanocomposites. An indigo emission peak from the nanocomposites and a red emission peak from the PS were observed in the case of the mesoporous ZnO/PS nanocomposites. At 10 K, the nanocomposites exhibited four emission peaks at 3.108, 2.929, 2.730, and 2.248 eV, which correspond to the DX, AX, DX-1LO, and DX-2LO phonon replicas, respectively. With an increase in temperature from 10 to 275 K, the curves in the intensities of the emission peaks formed an inverted "S" shape while their energies remained nearly constant. At 300 K, however, only the AX emission peak was observed; the DX and LO phonon replicas disappeared. The intensities of the DX and AX emission peaks exhibited anomalous behaviors.


NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.
Expression of the glutamine transporter SNAT3 increases in kidney during metabolic acidosis, suggesting a role during ammoniagenesis. Microarray analysis of Nrf2 knock-out (KO) mouse kidney identified Snat3 as the most significantly down-regulated transcript compared to wild-type (WT). We hypothesized that in the absence of NRF2 the kidney would be unable to induce SNAT3 under conditions of metabolic acidosis and therefore reduce the availability of glutamine for ammoniagenesis. Metabolic acidosis was induced for 7 days in WT and Nrf2 KO mice. Nrf2 KO mice failed to induce Snat3 mRNA and protein expression during metabolic acidosis. However, there were no differences in blood pH, bicarbonate, pCO2, chloride and calcium or urinary pH, ammonium and phosphate levels. Normal induction of ammoniagenic enzymes was observed whereas several amino acid transporters showed differential regulation. Moreover, Nrf2 KO mice during acidosis showed increased expression of renal markers of oxidative stress and injury and NRF2 activity was increased during metabolic acidosis in WT kidney. We conclude that NRF2 is required to adapt the levels of SNAT3 in response to metabolic acidosis. In the absence of NRF2 and SNAT3, the kidney does not have any major acid handling defect; however, increased oxidative stress and renal injury may occur.


Bacterial l-asparaginases for cancer therapy: Current knowledge and future perspectives.
l-Asparaginases hydrolyzing plasma l-asparagine and l-glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of l-asparaginase leading to their elimination. The l-asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma l-asparagine to inhibit the cancer cells growth; particularly among children. High level of l-asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy. Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by l-asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The l-asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi l-asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more l-asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects.


Electrocardiographic diagnosis of left ventricular hypertrophy improved by considering both QRS voltage and ST-T criteria.
We evaluated the usefulness of a combination of QRS voltage and the pattern of ST-T abnormality in the electrocardiographic diagnosis of left ventricular hypertrophy (LVH) in 100 middle-aged men: 32 normals, 59 with hypertension (HT), and 9 with hypertrophic cardiomyopathy (HCM) with evidence of LVH (RV5 or RV6 > or = 2.6 mV, SV1 + RV5 or SV1 + RV6 > or = 3.5 mV). They The subjects were classified into three groups based on ST-T pattern: normal (group N), early strain (group ES), and strain (group S). Echocardiographic evidence of LVH was present in 52.0% (52/100) of the subjects: 72.8% (43/59) of the patients with HT, all 9 patients with HCM, and none of the 32 normals. Echocardiographic evidence of LVH was present in 31.3% (20/64) of group N, 73.3% (11/15) of group ES, and all 21 subjects of group S. In patients with HT, the incidence of echocardiographic LVH was higher in group S (100%) than in both group ES (78.6%) and group N (60.6%). QRS voltage (RV5, RV6, RV5 + SV1, and RV6 + SV1) was significantly correlated with interventricular spetal thickness (IVST), IVST+LVPWT/2, and LV mass, as determined by echocardiography, in patients with LVH (IVST or left ventricular posterior wall thickness (LVPWT) of > or = 12 mm) (r = 0.55 to r = 0.75, p < 0.05), but not in patients without LVH (IVST and LVPWT < 12 mm). There were significant correlations between QRS voltage indices (RV5, RV6, RV5 + SV1, and RV6 + SV1) and IVST, IVST+LVPWT/2, and LV mass in group S (r = 0.68 to r = 0.86, p < 0.05), but not in group N. Values for IVST and LV mass were significantly greater in group S than in groups ES or N. The combination of QRS criteria and ST-T findings reflected the echocardiographic assessment of LVH, especially in patients with HT.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical and epidemiologic characteristics of severe childhood ocular injuries in southern iran.
To evaluate the clinical and epidemiological characteristics of children with ocular trauma. We retrospectively reviewed the medical records of 278 children (aged 15 years or less) hospitalized with ocular injuries and treated as inpatients at a tertiary referral center in Shiraz, Iran, from 2005 to 2008. Nominal variables were evaluated with a Chi-square test. A P-value less than 0.05 indicated statistical significance. The cohort was comprised of 205 (74%) males, outnumbering females by a ratio of 2.81/1. The mean age was 7.6 ± 3.96 years. Rural residents comprised 125 (45%) of the cohort. Sharp objects caused ocular injury in 211 (76%) cases, and 207 (74%) cases had open-globe injuries. The lens was injured in 62 (30%) cases at initial examination and 89 (43%) patients according to ultrasound examination (P = 0.006). Twenty-eight cases (10%) developed post-traumatic endophthalmitis. Endophthalmitis was associated with needle injury [odd ratio (OR) = 19.25] and presence of intraocular foreign body (OR = 3.48). Visual acuity of patients with closed-globe injuries was 20/200 or better on both initial and final examinations. Visual acuity of patients with open-globe injuries were in the range of light perception to 20/200. Trauma is an important cause of childhood ocular morbidity in southern Iran. Playing with sharp objects is an important cause of ocular trauma in children, and most injuries can be prevented by careful supervision.


Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations.
Primary prostate cancer can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we microdissected residual prostate cancer foci in radical prostatectomies from 18 men treated with neoadjuvant-intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) and analyzed them for resistance mechanisms. Transcriptome profiling showed reduced but persistent androgen receptor (AR) activity in residual tumors, with no increase in neuroendocrine differentiation. Proliferation correlated negatively with AR activity but positively with decreased RB1 expression, and whole-exome sequencing (WES) further showed enrichment for RB1 genomic loss. In 15 cases where 2 or 3 tumor foci were microdissected, WES confirmed a common clonal origin but identified multiple oncogenic alterations unique to each focus. These findings show that subclones with oncogenic alterations found in mCRPC are present in primary prostate cancer and are selected for by neoadjuvant-intense androgen deprivation therapy. In particular, this study indicates that subclonal RB1 loss may be more common than previously appreciated in intermediate- to high-risk primary prostate cancer and may be an early event, independent of neuroendocrine differentiation, in the development of mCRPC. Comprehensive molecular analyses of primary prostate cancer may detect aggressive subclones and possibly inform adjuvant strategies to prevent recurrence.Significance: Neoadjuvant androgen deprivation therapy for prostate cancer selects for tumor foci with subclonal genomic alterations, which may comprise the origin of metastatic castration-resistant prostate cancer. Cancer Res; 78(16); 4716-30. ©2018 AACR.


The resistance of polyelectrolyte multilayers in a free-hanging configuration.
The resistivity ρ(PEM) of polyelectrolyte multilayers (PEMs), PEI(PSS/PAH)(24), PEI(PGA/PAH)(12), PEI(HA/PLL)(12) and PEI(PSS/PLL)(12), in a free-hanging configuration was estimated combining electrochemical impedance spectroscopy (EIS) and atomic force microscopic (AFM) images. Surprisingly, the obtained value of several kΩcm is at least 6 orders of magnitude lower than that reported previously, where the resistivity was determined in the conventional PEM-on-electrode system. The significant discrepancy indicates the unexpectedly low electrical PEM resistance in the absence of redox-active ions and the sensitivity limitation in the conventional system.


The effects of school-based intervention programs on aggressive behavior: a meta-analysis.
Research on the effectiveness of school-based programs for preventing or reducing aggressive behavior was synthesized with a meta-analysis. Changes in aggressive behavior between pretest and posttest were analyzed for developmental patterns and characteristics associated with differential effects. Control groups showed little change in aggressive behavior, but there were significant reductions among intervention groups. Most studies were conducted on demonstration programs; the few studies of routine practice programs showed much smaller effects. Among demonstration programs, positive outcomes were associated with a variety of study, subject, and intervention characteristics. Most notably, higher risk youth showed greater reductions in aggressive behavior, poorly implemented programs produced smaller effects, and different types of programs were generally similar in their effectiveness, other things equal.


Chemical communication in spatially organized protocell colonies and protocell/living cell micro-arrays.
Micro-arrays of discrete or hemifused giant unilamellar lipid vesicles (GUVs) with controllable spatial geometries, lattice dimensions, trapped occupancies and compositions are prepared by acoustic standing wave patterning, and employed as platforms to implement chemical signaling in GUV colonies and protocell/living cell consortia. The methodology offers an alternative approach to GUV micro-array fabrication and provides new opportunities in protocell research and bottom-up synthetic biology.


Combinatorial ensemble miRNA target prediction of co-regulation networks with non-prediction data.
MicroRNAs (miRNAs) are key regulators of cell-fate decisions in development and disease with a vast array of target interactions that can be investigated using computational approaches. For this study, we developed metaMIR, a combinatorial approach to identify miRNAs that co-regulate identified subsets of genes from a user-supplied list. We based metaMIR predictions on an improved dataset of human miRNA-target interactions, compiled using a machine-learning-based meta-analysis of established algorithms. Simultaneously, the inverse dataset of negative interactions not likely to occur was extracted to increase classifier performance, as measured using an expansive set of experimentally validated interactions from a variety of sources. In a second differential mode, candidate miRNAs are predicted by indicating genes to be targeted and others to be avoided to potentially increase specificity of results. As an example, we investigate the neural crest, a transient structure in vertebrate development where miRNAs play a pivotal role. Patterns of metaMIR-predicted miRNA regulation alone partially recapitulated functional relationships among genes, and separate differential analysis revealed miRNA candidates that would downregulate components implicated in cancer progression while not targeting tumour suppressors. Such an approach could aid in therapeutic application of miRNAs to reduce unintended effects. The utility is available at http://rna.informatik.uni-freiburg.de/metaMIR/.


Comparative multi-assay evaluation of Determine™ HIV-1/2 Ag/Ab Combo rapid diagnostic tests in acute and chronic HIV infection.
In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I-VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests' antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II-III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.


Identification of Angiogenesis Inhibitors Using a Co-culture Cell Model in a High-Content and High-Throughput Screening Platform.
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells. The National Center for Advancing Translational Sciences (NCATS) Pharmaceutical Collection (NPC) library containing 2816 drugs was evaluated using the in vitro co-culture assay. From the screen, 35 potent inhibitors (IC50 ≤1 µM) were identified, followed by 15 weaker inhibitors (IC50 1-50 µM). Moreover, many known angiogenesis inhibitors were identified, such as topotecan, docetaxel, and bortezomib. Several potential novel angiogenesis inhibitors were also identified from this study, including thimerosal and podofilox. Among the inhibitors, some compounds were proved to be involved in the hypoxia-inducible factor-1α (HIF-1α) and the nuclear factor-kappa B (NF-κB) pathways. The co-culture model developed by using hTERT-immortalized cell lines described in this report provides a consistent and robust in vitro system for antiangiogenic drug screening.


Effect of the Presence of Antibiotic Residues on the Microbiological Quality and Antimicrobial Resistance in Fresh Goat Meat.
A total of 11 fresh goat legs were collected at the retail level. Mesophiles, Pseudomonas spp., Enterobacteriaceae, staphylococci, enterococci, Clostridium perfringens, Campylobacter spp., and Listeria monocytogenes counts were determined. Nine samples were free of antibiotic residues, while in the other two samples the presence of sulfadiazine and doxycycline was detected. The antimicrobial resistance of E. coli, staphylococci, Macrococcus spp., and enterococci isolates was also evaluated. Clostridium perfringens was found in two samples. Methicillin-resistant Staphylococcus aureus was detected in one sample. S. epidermidis isolated from one sample containing doxycycline residues showed resistance to mupirocin. Moreover, multi-resistant S. epidermidis and M. caseolyticus were found. Most of the isolated Enterococcus faecium were multi-resistant. Neither extended-spectrum β-lactamase -producing E. coli nor vancomycin-resistant enterococci were detected in any sample. The presence of doxycycline or sulfadiazine could affect the goat meat microbiota since less microbial diversity was found in these samples compared to those free of antibiotics. The presence of antibiotic residues could increase the antimicrobial resistance of enterococci in fresh goat meat. The presence of multidrug-resistant bacteria in goat meat could be considered a potential threat and should be monitored. Special measures should be taken at the farm level and during slaughter to reduce antimicrobial resistance.


Forced unbinding of individual urea-aminotriazine supramolecular polymers by atomic force microscopy: a closer look at the potential energy landscape and binding lengths at fixed loading rates.
Atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to study the forced unbinding of quadruple self-complementary hydrogen-bonded urea-aminotriazine (UAT) complexes in hexadecane (HD). To elucidate the bond strength of individual linkages the unbinding forces of UAT supramolecular polymers were investigated for the first time. The bond rupture was probed at three different, fixed piezo retraction rates in far from equilibrium conditions. The number of supramolecular bonds (N) between AFM tip and the surface was determined by independent knowledge of the linker length. The observed rupture force of urea-aminotriazine (UAT)-based supramolecular polymer chains was found to decrease with increasing rupture length. The dependence of the most probable rupture force on N was in quantitative agreement with the theory of uncooperative bond rupture for supramolecular linkages switched in series. Experiments with three different, fixed loading rates provided identical values (within the experimental error) for the characteristic bond length x(β) and the off-rate constant in the absence of force k(off)(f = 0). The value of x(β) was found to agree with literature data on the hydrogen-bond distance obtained via crystallographic data of the hydrogen-bonded dimer. This work broadens the scope of our previous report showing that relevant parameters of the bond energy landscape can be derived from a single data set of rupture events at a fixed loading rate for supramolecular linkages switched in series.


Executive summary.
The impact of dietary fats and oils on health continues to be a controversial subject. In addition, the ability of the food industry to freely alter the fat content and composition of foods to meet dietary recommendations is limited by how these food components affect food quality and stability. Therefore, a recent workshop was held to bring together food and nutrition scientists to highlight nutritional research and product innovations that explore the nutritional impact of fatty acids in the food supply. The latest research on metabolic responses and health benefits associated with foods made with new nutritional and functional oils was discussed, along with a detailed look at how science-based advances in preparation methods and processing technologies affect the nutrient profile of food products, including potato products. Additional discussion was provided on how oil innovations align with dietary guidance and policy. This supplement issue presents articles on those presentations.


Acetylene-Triggered Reductive Incorporation of Phosphine Chalcogenides into a Quinoline Scaffold: Toward SNHAr Reaction.
Quinolines react with acylacetylenes and secondary phosphine chalcogenides at 20-75 °C to afford N-acylvinyl-2(1)-chalcogenophosphoryldihydroquinolines in good and excellent yields. Unlike the pyridine-derived similar intermediates, which eliminate E-alkenes to give aromatic chalcogenophosphorylpyridines, thereby completing SNHAr reaction, with quinolines, the reaction stops at the formation of the above phosphorylated N-acylvinyl-dihydroquinolines, thus representing a pendant SNHAr process. This reaction opens a one-pot atom-economic single-step access to pharmaceutically targeted phosphorylated functionalized dihydroquinolines and isoquinolines.


Risk factors predisposing to fetal loss following a second trimester amniocentesis.
To examine the influence of possible risk factors on fetal loss rate following amniocentesis. Retrospective analysis of case records between 1993 and 1998. Fetal medicine unit of a large teaching hospital. One thousand and six women with singleton pregnancies formed the study group. Seven hundred and eight of them had bleeding during the current pregnancy before the procedure. while 298 had a history of three or more first trimester abortions and/or a second trimester miscarriage or termination of pregnancy. Four thousand and twenty-four women who had amniocentesis and had no risk factors served as controls. Both groups were also classified according to maternal age. Group 1:1,610 women aged 20-34 years; Group 2: 2850 women aged 35-39 years; Group 3; 570 women > 40 years. Women of both groups underwent a second trimester amniocentesis between 16 and 21 weeks of gestation. Fetal losses following amniocentesis were examined in three time intervals: 1. in the first two weeks after the procedure; 2. up to the 28th week; 3. from the 28th week to term. There was a statistically significant difference in the fetal loss rate between women aged 20-34 years (2.54%) and those > 40 years (5.1%). Women with a history of vaginal bleeding during the current pregnancy had a higher fetal loss rate compared with controls (6.5% vs 2.8%), which corresponds to an odds ratio of 2.4 (95% CI 1.69-3.42). A similar difference was found between the group of women with a history of previous abortions/terminations and the controls (8% vs 2.8%): OR 3.03 (95% Cl 1.92-4.79). There is a higher risk of fetal loss following amniocentesis in women > 40 years of age compared with those aged 20-34 years. Bleeding in the current pregnancy, a history of three or more first trimester abortions, a second trimester miscarriage or termination of pregnancy seem to be significant predisposing factors for fetal loss after an amniocentesis.


Diastereoselective Synthesis of Tetrahydroquinolines via [4 + 2] Annulation between in Situ Generated p-Quinone Methides and Nitroalkenes.
A formal [4 + 2] annulation reaction between in situ generated p-quinone methides and nitroalkenes via an aza-Michael/1,6-conjugate addition reaction sequence has been developed in which manganese dioxide is used as the oxidant to promote in situ formation of o-tosylaminophenyl-substituted p-QMs. Under mild conditions, this unprecedented cascade reaction readily occurs in good yield, providing straightforward access to a series of 4-aryl-substituted tetrahydroquinolines.


Tetanus in England and Wales, 1984-2000.
A review of national tetanus surveillance in England and Wales during 1984-2000 was undertaken to evaluate the surveillance system and national vaccination policy. Hospital Episode Statistics for tetanus in England for fiscal years 1989/90-1995/6 were also examined to estimate under-reporting. A total of 175 cases of tetanus were reported, giving an annual incidence of 0.20 per million, the lowest levels ever recorded. The highest incidence was in those aged over 64 years (0.66 per million) with no significant sex difference. Twenty (11%) cases were reported in people who were eligible for routine childhood vaccination. Outdoor injuries were the commonest reported exposure risk. Tetanus case under-reporting was estimated as 54-64%. We conclude that GPs should ensure that all their patients are fully vaccinated, targeting those born before 1961. High childhood tetanus vaccination coverage remains a priority. As the disease becomes rarer, enhanced tetanus case surveillance is essential for tetanus immunization policy evaluation.


Ephedrine hydrochloride protects mice from staphylococcus aureus-induced peritonitis.
Staphylococcus aureus is a Gram-positive (G+) bacterium that causes a wide range of diseases in humans and livestock. Therefore, the development of innovative and effective therapies is essential for the treatment of S. aureus-induced severe infections. Ephedrine hydrochloride (EH) is a compound derived from ephedrine and is widely used for the management of cardiovascular diseases and hypotension. The results of our previous studies demonstrated that EH has anti-inflammatory activity in macrophages and protects against endotoxic shock. However, whether EH regulates the function of dendritic cells (DCs) and the immune response in S. aureus-induced infection is unknown. In this study, the anti-inflammatory and regulatory activity of EH on DCs was evaluated. EH increased the production of anti-inflammatory cytokine IL-10 and decreased the production of proinflammatory cytokines TNF-α and IL-12 in DCs stimulated with peptidoglycan (PGN), the main cell wall component in G+ bacteria. The PI3K/Akt and p38 MAPK signaling pathways controlled EH-induced IL-10 expression and EH-inhibited TNF-α expression, respectively. The PGN-induced expression of co-stimulatory molecules CD40, CD80, CD86, and MHC class II molecule Iab was down-regulated in DCs by EH. Furthermore, EH protected the liver and kidney and increased the survival rate of mice with S. aureus-induced peritonitis. In conclusion, EH helps to keep immune homeostasis and alleviate organ damage during S. aureus-induced peritonitis. Therefore, EH may be a promising drug candidate in the treatment of S. aureus-induced severe infections and other invasive G+ bacterial infections.


Antibacterial electrospun poly(ɛ-caprolactone)/ascorbyl palmitate nanofibrous materials.
The one-step incorporation of ascorbyl palmitate (AP), a widely used derivative of vitamin C, into nanofibrous mats of poly(ɛ-caprolactone) (PCL) by electrospinning was demonstrated. The incorporation of AP was attested by IR spectroscopy; the AP content was determined by thermogravimetric analysis (TGA); and the surface composition of the mats: by X-ray photoelectron spectroscopy (XPS). The possibility for deposition of silver nanoparticles onto PCL/AP mats using the ability of AP to reduce silver ions was demonstrated. The silver content was determined by TGA, and the silver nanoparticles were observed by transmission electron microscopy (TEM). The nanoparticles were composed of elemental silver, as verified by XPS analyses. The UV-vis spectrophotometric analyses, study on quenching of the free 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and microbiological tests against the pathogenic microorganism Staphylococcus aureus showed that AP preserved its stability and its antioxidant and antibacterial activity when incorporated in the nanofibrous mats.


Effect of anticonvulsants on cortical focal seizure in cats.
Electrical stimulation of the visual cortex evoked the cortical focal seizure restricted in the neighbor cortex of the stimulated area in gallamine-immobilized cats. The present experiment was performed to clarify the participation of anticonvulsants in the cortex itself. Phenytoin and carbamazepine depressed the focal seizure, as indicated by the shortening of seizure duration and the suppression of spreading. In addition, the high-frequency components in seizure disappeared with the use of these drugs. Phenobarbital and diazepam also shortened the seizure duration. However, the high-frequency components did not disappear although seizure amplitude was depressed. Trimethadione, acetazolamide, and dipropylacetate facilitated the focal seizure. From these results, the participation of the drugs affecting grand mal and partial epilepsies in the cortex is suggested. In addition, this experimental model is though to be useful in elucidating possible modes or mechanisms of anticonvulsant action on cortical neurons by analyzing, after drug administration, the changes in seizure patterns which seem to reflect underlying neuronal changes.


Clinical Data for Informed Medication Use in Pregnancy: Strengths, Limitations, Gaps, and a Need to Continue Moving Forward.
The objective of this paper is to explore the strengths, weaknesses, gaps, and needs in research on medication use in pregnancy, where opportunities have been bypassed to develop standards and collaborations for collecting data to better understand how medications can impact clinical outcomes in pregnant women and developing fetuses. The availability of existing data and the methods of its capture are reviewed, including registries, claims and health record databases, and meta-analyses. The paper focuses on why these efforts have not fundamentally provided benefit-risk information and clinical treatment algorithms for medication use in pregnant women. Methodological issues, such as lack of standardization and central data collection, are discussed. Common barriers are examined, including a lack of awareness and education, cultural hurdles, collaboration deficiency, and an insufficient development of new data collection methods.


Autopsy findings in conjoined twin with single heart and single liver.
Thoracoomphalopagus is the commonest type of conjoined twin where the bodies are fused from upper chest to lower chest. The autopsy done can help counsil the parents for further pregnancies and determine the prognosis depending upon the type of cardiac anomaly by Seo classification when detected antenatally. We describe the detail pathological autopsy of such a case with single heart and single liver. A detail autopsy was done on the twin fetus. The twins shared a single heart and sometimes the liver and part of digestive system. The combined weight was 4.1 KG. Both were full-term male babies joined from below the nipple till umbilicus. Autopsy in conjoined twins helps in deciding the type of fusion of the body and also of the heart and great vessels. It can help in counseling parents about future pregnancies that there is no chance of recurrence of this abnormality and no need to be scared.


Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients.
Weight loss and anorexia are frequent findings in advanced cancer. The progressive wasting could be attributed to changes in dietary intake and/or energy expenditure mediated by metabolic alterations. In this study, we analyzed dietary intake in generalized malignant disease of solid tumor type in relation to resting energy expenditure (REE) and reported weight loss. In a group of 297 unselected cancer patients from a university hospital outpatient clinic, dietary intake of energy and macronutrients from a 4-day food record, REE by indirect calorimetry, height, weight and weight loss were recorded. Protein intake was validated against 24 hr urine nitrogen in a subgroup (n = 53), and no indication of systematic misreporting was found. Mean daily dietary intake was below maintenance requirements, 26 +/- 10 kcal/kg. Weight loss of more than 10% was present in 43% of patients and elevated REE (>110% of predicted) in 48%. Dietary intake did not differ between normo- and hypermetabolic patients, nor was tumour type or gender related to energy and protein intake. Weight loss could not be accounted for by diminished dietary intake since energy intake in absolute amounts was not different and intake per kilogram body weight was higher in weight-losing patients compared to weight-stable patients. Dietary macronutrient composition did not differ from the general population. Dietary intake of energy and protein was decreased, but dietary macronutrient composition did not appear to be changed. Weight loss and hypermetabolism were frequent and not compensated for by an increase in spontaneous food intake. Our results indicate that an expected up-regulation of dietary intake in response to elevated energy expenditure is frequently lost in cancer patients. This may be the explanation behind cancer cachexia rather than a primary decrease in appetite.


Characterization of relapsing-remitting multiple sclerosis patients using support vector machine classifications of functional and diffusion MRI data.
Multiple Sclerosis patients' clinical symptoms do not correlate strongly with structural assessment done with traditional magnetic resonance images. However, its diagnosis and evaluation of the disease's progression are based on a combination of this imaging analysis complemented with clinical examination. Therefore, other biomarkers are necessary to better understand the disease. In this paper, we capitalize on machine learning techniques to classify relapsing-remitting multiple sclerosis patients and healthy volunteers based on machine learning techniques, and to identify relevant brain areas and connectivity measures for characterizing patients. To this end, we acquired magnetic resonance imaging data from relapsing-remitting multiple sclerosis patients and healthy subjects. Fractional anisotropy maps, structural and functional connectivity were extracted from the scans. Each of them were used as separate input features to construct support vector machine classifiers. A fourth input feature was created by combining structural and functional connectivity. Patients were divided in two groups according to their degree of disability and, together with the control group, three group pairs were formed for comparison. Twelve separate classifiers were built from the combination of these four input features and three group pairs. The classifiers were able to distinguish between patients and healthy subjects, reaching accuracy levels as high as 89% ± 2%. In contrast, the performance was noticeably lower when comparing the two groups of patients with different levels of disability, reaching levels below 63% ± 5%. The brain regions that contributed the most to the classification were the right occipital, left frontal orbital, medial frontal cortices and lingual gyrus. The developed classifiers based on MRI data were able to distinguish multiple sclerosis patients and healthy subjects reliably. Moreover, the resulting classification models identified brain regions, and functional and structural connections relevant for better understanding of the disease.


The evolution of introns in human duplicated genes.
In previous work [Jabbari, K., Rayko, E., Bernardi, G., 2003. The major shifts of human duplicated genes. Gene 317, 203-208], we investigated the fate of ancient duplicated genes after the compositional transitions that occurred between the genomes of cold- and warm-blooded vertebrates. We found that the majority of duplicated copies were transposed to the "ancestral genome core", the gene-dense genome compartment that underwent a GC enrichment at the compositional transitions. Here, we studied the consequences of the events just outlined on the introns of duplicated genes. We found that, while intron number was highly conserved, total intron size (the sum of intron sizes within any given gene) was smaller in the GC-rich copies compared to the GC-poor copies, especially in dispersed copies (i.e., copies located on different chromosomes or chromosome arms). GC-rich copies also showed higher densities of CpG islands and Alus, whereas GC-poor copies were characterized by higher densities of LINEs. The features of the copies that underwent the compositional transition and became GC-richer are suggestive of, or related to, functional changes.


Cryptococcal Protease(s) and the Activation of SARS-CoV-2 Spike (S) Protein.
In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, SPRRAR↓S) at the interface between the S1 and S2 sites, that serves as a cleavage site for the human protease, furin. We compared the biochemical efficiency of cryptococcal protease(s) and furin to mediate the proteolytic cleavage of the S1/S2 site in a fluorogenic peptide. We show that cryptococcal protease(s) processes this site in a manner comparable to the efficiency of furin (p > 0.581). We conclude the paper by discussing the impact of these findings in the context of a SARS-CoV-2 disease manifesting while there is an underlying cryptococcal infection.


Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?
The diagnosis and treatment of pituitary disease in pregnancy represents a special clinical challenge. Not least because there is very little data on the treatment of pregnant patients with pituitary disorders. A selective search of the literature was carried out with the aim of compiling evidence about the diagnosis and treatment of pituitary disease in pregnancy. The search covered the databases PubMed/MEDLINE including PubMed Central and also used the Livivo (ZB MED) search engine. Recent studies were evaluated for recommendations about the care of pregnant patients with hormone-inactive and hormone-active pituitary adenomas (prolactinoma, acromegaly and Cushing's disease), pituitary insufficiency, pituitary apoplexy and hypophysitis. The most well-established forms of treatment are for prolactinoma, due to the incidence of this disease and its impact on fertility. When pregnancy has been confirmed, prolactinoma treatment with dopamine agonists should be paused. Although microprolactinomas rarely increase significantly in size after the administration of dopamine agonists is discontinued, symptomatic tumor growth of macroprolactinomas can occur. In such cases, treatment with dopamine agonists can be resumed. If the primary tumor is large and the risk that it will continue to grow is high, it may be necessary to continue medical treatment from the start of pregnancy. If one of the partners has a pituitary disorder, it is often still possible for many couples to achieve their wish of having children if they receive medical support to plan and the pregnancy is carefully monitored. Given the complexity of pituitary disease, pregnant patients with pituitary disorders should be cared for and treated by a multidisciplinary team in centers specializing in the diagnosis and treatment of pituitary disease.


A note on chirality in NMR spectroscopy.
Using simple symmetry arguments we give proofs of the derivations of the manifestation of chirality in the chemical shift and spin-spin coupling constant in nuclear magnetic resonance and relate our proofs to earlier discussions.


Neonatal Perforated Appendicitis Attributed to Localized Necrotizing Enterocolitis of the Appendix: A Review.
Neonatal appendicitis is a rare clinical entity associated with remarkable morbidity and mortality. Appendicular perforation is common and the diagnosis is usually made intra-operatively. The causative etiology of neonatal perforated appendicitis (NPA) is a subject of debate and has not been elucidated. Although many etiologic theories exist, increasing evidence suggests a subset of NPA cases may represent a form of necrotizing enterocolitis (NEC) localized to the appendix. We herein present a review of the current literature to include cases of NPA attributed to localized NEC. A high index of clinical suspicion and early laparotomy are recommended.


The response of ataxia-telangiectasia lymphoblastoid cells to neutron irradiation.
The response of control and ataxia-telangiectasia (A-T) cells to increasing doses of high-linear-energy-transfer (LET) ionizing radiation (neutrons) was compared. Ataxia-telangiectasia cells were markedly more sensitive to neutron irradiation than were control cells. The D0 value for the two A-T cell lines was 0.4 Gy while the value for controls was approximately 1.4 Gy. Fast neutrons were considerably more effective than gamma rays in inducing cell death in both cell types, but the sensitivity factor remained approximately the same as with gamma rays. A minimal depression of DNA synthesis was observed in ataxia-telangiectasia cells after neutron irradiation, similar to that reported previously after gamma irradiation. The extent of inhibition was not significantly greater in control cells, contrary to that seen with gamma rays. In time-course experiments a significant difference in degree of inhibition of DNA synthesis was observed between the cell types. Low doses of fast neutrons induced a G2-phase delay in both cell types, but the degree and extent of this delay was greater in ataxia-telangiectasia cells as observed previously with low-LET radiation.


Transpositional microsurgery in multiple digital amputations.
In 34 of the 62 patients treated for complete multiple digital amputations, the severed part was not replanted in its anatomical position, but in the place of the most useful stump. This procedure is defined as transpositional digital microsurgery and refers to the transposition and replantation of any digit to another stump which plays a more significant role in the function of the hand. Twenty-eight patients had transposition of a digit, while six patients underwent thumb transposition. All except six of the transposed digits survived, while all of the thumbs survived the surgical procedure. The cosmetic appearance of the hand with a transposed digit or thumb was acceptable to the patients. Two-point discrimination was assessed to be 10-14 mm for the transposed digits, and the functional ability of the transplanted digit was comparable to digits which were replanted in their anatomical position. In conclusion, transpositional digital microsurgery remains a useful alternative for the treatment of multiple digit amputations, particularly in patients with severely damaged non-replantable amputated parts.


Indications and outcomes of intrauterine surgery for fetal malformations.
Although the efficacy of intrauterine intervention has been clearly demonstrated for some conditions, such as twin to twin transfusion syndrome and twin reversal arterial perfusion, it is still to be determined as treatment of congenital diaphragmatic hernia, cardiac defects, lower urinary tract obstruction and sacrococcygeal teratoma. The aim of the present study was to review literature concerning the benefits and outcomes of fetal intervention for these anomalies together with its limitations and controversies. Only one randomized clinical trial, which compared prenatal versus postnatal treatment for congenital diaphragmatic hernia, was performed. For the other anomalies, small series were described and showed that fetal surgery drastically changes the natural history of the discussed anomalies, thus it prevents the progression of a disorder that is likely to be fatal. However, controversies exist with regard to operating timing and selection criteria of fetuses that may benefit from fetal surgery. Further investigations are needed with regard to the definition of appropriate operating timing and standardization of selection criteria. Multicenter randomized trials are also necessary in order to define whether fetal surgery is associated with better outcomes as compared with postnatal treatment.