Jingfang granule alleviates Pseudomonas aeruginosa-induced acute lung inflammation through suppression of STAT3/IL-17/NF-κB pathway based on network pharmacology analysis and experimental validation.
Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the second leading cause of hospital-acquired pneumonia. Jingfang granule (JFG) is an herbal formula of Traditional Chinese medicine (TCM) widely used in treatment of acute respiratory tract infections in China. However, the molecular mechanisms of JFG in treatment of P. aeruginosa-induced acute pneumonia are not clear. This study aimed to investigate the mechanisms underlying the effects of JFG on P. aeruginosa-induced acute inflammation using a mouse model of bacterial acute pneumonia. The chemical components and targets of JFG were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the P. aeruginosa pneumonia-related targets were obtained from the disease databases, including Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNet. The protein-protein interaction (PPI) network was constructed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Molecular docking was performed using AutoDockTools 1.5.6. Further in vivo experiments employed a mouse model of P. aeruginosa acute pneumonia to verify the target proteins and signaling pathways affected by JFG, which were predicted by the network pharmacology analysis. A total of 218 active components and 257 targets of JFG were retrieved from TCMSP database. Moreover, 99 intersectant targets were obtained between the 257 JFG targets and 694 disease targets. Among the intersectant targets, STAT3, IL-6, AKT1, TNF, MAPK1, MAPK3 and EGFR were identified to be the key therapeutic targets through PPI network analysis, and STAT3 was in the center of the network, which is a key regulator of IL-17 expression. KEGG pathway enrichment analysis suggested that IL-17 signaling pathway was one of the crucial inflammatory pathways affected by JFG in treatment of P. aeruginosa pneumonia. Furthermore, the in vivo experiments demonstrated that the JFG-treated mice displayed reduced proinflammatory cytokine production (IL-17, IL-1β, IL-6 and TNF), diminished neutrophil infiltration and decreased mortality, compared with the non-drug-treated mice during P. aeruginosa lung infection. Moreover, the expression or phosphorylation levels of the key regulators in STAT3/IL-17/NF-κB axis including STAT3, ERK1/2 (MAPK3/1), AKT, NF-κB p65 and RORγt were significantly reduced in the lung tissues of the JFG-treated mice. JFG was effective in treatment of P. aeruginosa acute lung infection, which reduced inflammatory responses through suppressing STAT3/IL-17/NF-κB pathway.


Intermittent androgen deprivation therapy in advanced prostate cancer.
Prostate cancer is an androgen driven cancer. Androgen deprivation therapy (ADT) has been the standard first line therapy for metastatic prostate cancer. Medical castration with Luteinizing hormone releasing hormone (LHRH) agonists and more recently LHRH antagonists has largely supplanted surgical castration. Key issues in optimizing ADT have been timing of ADT initiation in metastatic prostate cancer (early vs deferred), monotherapy with LHRH agonist alone vs combination therapy with an anti-androgen, and the schedule of medical castration (intermittent vs continuous). After numerous trials attempting to clarify the role of anti-androgens in initial therapy of metastatic prostate cancer with conflicting results on survival benefit with combination therapy, meta-analyses suggest a small but measurable prolongation in overall survival. The lower incidence of severe adverse events including cord compression in advanced prostate cancer with early ADT has established immediate initiation of ADT upon diagnosis of metastatic prostate cancer as standard clinical practice. The schedule of ADT has been the subject of extensive investigation spurred by early preclinical work suggesting continuous pressure of castration promoted development of castration resistance. Trials testing intermittent ADT in several clinical contexts including in patients with biochemical recurrence, suggested intermittent ADT is comparable to continuous ADT. However, except for the JPR7, trials had mixed patient populations and/or were not powered for overall survival (OS). The only OS powered large phase 3 trial in metastatic disease (INT-0162/SWOG-9346) demonstrated that survival with intermittent ADT is not comparable to that with continuous therapy. Continuous ADT therefore continues to be the standard; however, therapy should be tailored to a patient's individual needs with adequate counseling. Novel inhibitors of androgen synthesis including abiraterone and androgen receptor antagonists such as enzalutamide, and cytotoxic chemotherapy already proven to be effective in castration resistant prostate cancer are under investigation in hormone sensitive prostate cancer. If validated, they would represent a long overdue paradigm shift in advanced hormone sensitive prostate cancer management.


Regulating private health insurance to serve the public interest: policy issues for developing countries.
Private health insurance plays a large and increasing role around the world. This paper reviews international experiences and shows that private health insurance is significant in countries with widely different income levels and health system structures. It contrasts trends in private health insurance expansion across regions and highlights countries with particularly important experiences of private coverage. It then discusses the regulatory approaches and policies that can structure private health insurance markets in ways that mobilize resources for health care, promote financial risk protection, protect consumers and reduce inequities. The paper argues that policy makers need to confront the role that private health insurance will play in their health systems and regulate the sector appropriately so that it serves public goals of universal coverage and equity.


A Simple Method of VNTR D1S80 Locus Allelic Ladder Construction for Capillary Electrophoresis-based Genotyping.
VNTR D1S80 locus genotyping has been largely replaced in forensics by STR. As the statute of limitations on murder cases was abolished in the Republic of Korea in July 2015, the demand for re-analysis of DNA from unresolved murder cases has increased. The National Forensic Service includes several recorded D1S80 genotypes as crucial clues. Here, we re-established the D1S80 analysis system using capillary electrophoresis and confirmed the reproducibility of the system by comparison with the genotypes of eight DNA samples that had been analyzed using PAGE in 2006. In addition, we created an allelic ladder via new methodology using flanking region sequences. A single DNA sample (K562) and seven primers were used for the new ladder, which contains 12 alleles. Although artificial owing to the use of the flanking region rather than repeat unit reduction, the method is rapid and simple, and could be applicable in any laboratory.


Paramagnetic resonance of biological metal centers.
The review deals with recent advances in magnetic resonance spectroscopy (hf EPR and NMR) of paramagnetic metal centers in biological macromolecules. In the first half of our chapter, we present an overview of recent technical developments in the NMR of paramagnetic bio-macromolecules. These are illustrated by a variety of examples deriving mainly from the spectroscopy of metalloproteins and their complexes. The second half focuses on recent developments in high-frequency EPR spectroscopy and the application of the technique to copper, iron, and manganese proteins. Special attention is given to the work on single crystals of copper proteins.


Development and Initial Validation of a Multidimensional Scale Assessing Subjective Well-Being: The Well-Being Scale (WeBS).
Numerous scales currently exist that assess well-being, but research on measures of well-being is still advancing. Conceptualization and measurement of subjective well-being have emphasized intrapsychic over psychosocial domains of optimal functioning, and disparate research on hedonic, eudaimonic, and psychological well-being lacks a unifying theoretical model. Lack of systematic investigations on the impact of culture on subjective well-being has also limited advancement of this field. The goals of this investigation were to (1) develop and validate a self-report measure, the Well-Being Scale (WeBS), that simultaneously assesses overall well-being and physical, financial, social, hedonic, and eudaimonic domains of this construct; (2) evaluate factor structures that underlie subjective well-being; and (3) examine the measure's psychometric properties. Three empirical studies were conducted to develop and validate the 29-item scale. The WeBS demonstrated an adequate five-factor structure in an exploratory structural equation model in Study 1. Confirmatory factor analyses showed that a bifactor structure best fit the WeBS data in Study 2 and Study 3. Overall WeBS scores and five domain-specific subscale scores demonstrated adequate to excellent internal consistency reliability and construct validity. Mean differences in overall well-being and its five subdomains are presented for different ethnic groups. The WeBS is a reliable and valid measure of multiple aspects of well-being that are considered important to different ethnocultural groups.


Successful Reduction of Intraocular Pressure in a Patient with Glaucoma Secondary to Sturge-Weber Syndrome Using a Suprachoroidal Shunt.
We present a case of successful reduction of intraocular pressure (IOP) in a patient with Sturge-Weber syndrome (SWS) and moderate open angle glaucoma using a suprachoroidal shunt. Patients with SWS glaucoma often have elevated episcleral venous pressure resulting in elevated IOP. This makes the conventional pathway for aqueous humor outflow a poor target for IOP reduction, yielding it difficult to treat. Medication and procedures that facilitate uveoscleral outflow have been more successful. We present a case where a suprachoroidal shunt device (CyPass®) was used to reduce IOP in a patient with SWS. The IOP reduction has persisted for 12 months without complication or the requirement for topical prostaglandin analog use. The uveoscleral pathway is a preferred target for IOP reduction in patients with elevated episcleral venous pressure. The CyPass device offers a promising ab interno minimally invasive glaucoma surgery (MIGS) approach to reduce IOP in cases where a pathologic pressure gradient exists in the trabecular meshwork. Glaucoma in patients with SWS has been historically difficult to treat. Previous surgical procedures that have been successful are more invasive and have required the creation of alternative drainage routes of aqueous humor. The CyPass device offers a promising less invasive option to reduce IOP in these patients. Junttila TL, Alberto N, Winkels M, et al. Successful Reduction of Intraocular Pressure in a Patient with Glaucoma Secondary to Sturge-Weber Syndrome Using a Suprachoroidal Shunt. J Curr Glaucoma Pract 2020;14(1):43-46.


The effect of operating and formulation variables on the morphology of spray-dried protein particles.
The purpose of this research was to investigate the shape and morphology of various spray-dried protein powders as a function of spray-drying conditions and protein formulations. A benchtop spray dryer was used to spray dry three model proteins in formulation with a sugar or a surfactant. Physical characterizations of the powder included morphology (scanning electron microscopy), particle size, residual moisture, and X-ray powder diffraction analyses. A significant change in particle shape from irregular (e.g., "donut") to spherical was observed as the outlet temperature of the dryer was decreased. The drying air outlet temperature was shown to depend on various operating parameters and was found to correlate with the drying rate of atomized droplets in the drying chamber. The morphology of spray-dried protein particles was also affected by formulation. In protein:sugar formulations, spray-dried particles exhibited a smooth surface regardless of the protein-to-lactose ratio, whereas roughness was observed when mannitol was present at > 30% of total solids, due to recrystallization. Protein particles containing trehalose at concentrations > 50% were highly agglomerated. The presence of surfactant resulted in noticeably smoother, more spherical particles. The shape and the morphology of spray-dried powders are affected by spray drying conditions and protein formulation. This study provides information useful for development of dry proteins for fine powder (e.g., aerosol) applications.


Understanding bulimia.
Bulimia nervosa (BN) and related eating disorders such as binge eating disorder are common. General practitioners can play a key role in the identification and management of BN and related eating disorders. This article describes the presenting and associated features of BN and overviews evidence based treatment approaches. Key features are recurrent episodes of binge eating, extreme weight control behaviours and over concern about weight and shape issues. By definition people are not underweight. Risk factors include being from a western culture, obesity, exposure to a restrictive dieting environment and low self esteem. People are more likely to present asking for help in weight control or a physical problem secondary to the eating disorder. Evidenced based therapies with good outcomes in current use are cognitive behaviour therapy (in full or guided self help forms), high dose fluoxetine, and interpersonal psychotherapy. It is important to convey optimism about treatment efficacy and outcomes.


Gas Chromatography/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry for Fingerprinting the Macondo Oil Spill.
We report the first application of a new mass spectrometry technique (gas chromatography combined to atmospheric pressure chemical ionization tandem mass spectrometry, GC/APCI-MS/MS) for fingerprinting a crude oil and environmental samples from the largest accidental marine oil spill in history (the Macondo oil spill, the Gulf of Mexico, 2010). The fingerprinting of the oil spill is based on a trace analysis of petroleum biomarkers (steranes, diasteranes, and pentacyclic triterpanes) naturally occurring in crude oil. GC/APCI enables soft ionization of petroleum compounds that form abundant molecular ions without (or little) fragmentation. The ability to operate the instrument simultaneously in several tandem mass spectrometry (MS/MS) modes (e.g., full scan, product ion scan, reaction monitoring) significantly improves structural information content and sensitivity of analysis. For fingerprinting the oil spill, we constructed diagrams and conducted correlation studies that measure the similarity between environmental samples and enable us to differentiate the Macondo oil spill from other sources.


Salmonella and Arizona from snakes in the Judean desert (1974-1975).
Ninety-four (77.7%) of the 121 snakes captured during the years 1974-1975 in the Judean desert were found to carry Salmonella and/or Arizona organism. Sixty-six snakes (54.4%) harboured only one serotype. From 19 animals (15.7%) both Salmonella and Arizona organisms were isolated. From 9 snakes (7.5%) 2 or 3 serotypes of Arizona were isolated. Only 27 snakes (22,3%) harboured no detectable Salmonella nor Arizona in their intestinal contents.


Altered synaptic plasticity in a mouse model of fragile X mental retardation.
Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.


Polyelectrolyte complex membranes for immobilizing biomolecules, and their applications to bio-analysis.
The immobilization of biomolecules is an important technique for bio-analysis, and can be applied to biosensors with both high selectivity and high sensitivity. Many researchers have developed immobilization techniques to optimize these characteristics. In the last two decades, an immobilization technique that meets the desired requirements was developed by using polyelectrolytes to form complexes, based on the electrostatic binding between polycations and polyanions. This review summarizes the techniques used for the immobilization of biomolecules by polyelectrolyte complexes; it also discusses related subjects.


Quinolinic Acid Amyloid-like Fibrillar Assemblies Seed α-Synuclein Aggregation.
Quinolinic acid (QA), a downstream neurometabolite in the kynurenine pathway, the biosynthetic pathway of tryptophan, is associated with neurodegenerative diseases pathology. Mutations in genes encoding kynurenine pathway enzymes, which control the level of QA production, are linked with elevated risk of developing Parkinson's disease. Recent findings have revealed the accumulation and deposition of QA in post-mortem samples, as well as in cellular models of Alzheimer's disease and related disorders. Furthermore, intrastriatal inoculation of mice with QA results in increased levels of phosphorylated α-synuclein and neurodegenerative pathological and behavioral characteristics. However, the cellular and molecular mechanisms underlying the involvement of QA accumulation in protein aggregation and neurodegeneration remain elusive. We recently established that self-assembled ordered structures are formed by various metabolites and hypothesized that these "metabolite amyloids" may seed amyloidogenic proteins. Here we demonstrate the formation of QA amyloid-like fibrillar assemblies and seeding of α-synuclein aggregation by these nanostructures both in vitro and in cell culture. Notably, α-synuclein aggregation kinetics was accelerated by an order of magnitude. Additional amyloid-like properties of QA assemblies were demonstrated using thioflavin T assay, powder X-ray diffraction and cell apoptosis analysis. Moreover, fluorescently labeled QA assemblies were internalized by neuronal cells and co-localized with α-synuclein aggregates. In addition, we observed cell-to-cell propagation of fluorescently labeled QA assemblies in a co-culture of treated and untreated cells. Our findings suggest that excess QA levels, due to mutations in the kynurenine pathway, for example, may lead to the formation of metabolite assemblies that seed α-synuclein aggregation, resulting in neuronal toxicity and induction of Parkinson's disease.


Growth monitoring still has a place in selected populations of children.
In 1998, a multiprofessional group developed a consensus on growth monitoring in the UK. While routine serial measurements were not recommended in healthy children, it is clear that there is a subset of children at increased risk of growth-modifying disease who may benefit from growth monitoring. This subset includes children with genetic disorders at increased risk of thyroid dysfunction. Symptoms and signs of thyroid dysfunction are non-specific in the early stages of disease and are easily mistaken for features of an underlying genetic disorder. In this article, we report the case of a 2.8-year-old girl with 18q deletion syndrome who was profoundly weak, hypotonic and poorly responsive at diagnosis of Grave's disease. She was tall and her bone age was 2 years advanced, indicating long-standing disease. Growth monitoring of this patient should have enabled earlier diagnosis and avoided a serious and potentially fatal episode.


Analysis of Dependently Truncated Data in Cox Framework.
Truncation is a known feature of bone marrow transplant (BMT) registry data, for which the survival time of a leukemia patient is left truncated by the waiting time to transplant. It was recently noted that a longer waiting time was linked to poorer survival. A straightforward solution is a Cox model on the survival time with the waiting time as both truncation variable and covariate. The Cox model should also include other recognized risk factors as covariates. In this paper we focus on estimating the distribution function of waiting time and the probability of selection under the aforementioned Cox model.


The effect of muscarinic and beta-adrenergic blockade on cysteamine-induced gastrin secretion by the isolated perfused rat stomach.
Cysteamine-induced duodenal ulceration in rats is accompanied by increased circulating gastrin. Although cysteamine appears to exert a direct action on the gastrin cell some groups have provided evidence for an involvement of the autonomic nervous system. The current experiments were performed to determine whether beta-adrenergic or cholinergic (muscarinic) pathways are involved in the acute effect of cysteamine on gastrin secretion in the isolated perfused rat stomach. Cysteamine (1 mM) increased gastrin (IRG) secretion to a maximum ranging between 100% and 192% above basal. A cysteamine concentration of 5mM resulted in peak levels ranging between 150% and 1050% above basal. Addition of atropine or propranalol did not influence the responses obtained. The present results, therefore, do not support a role for either cholinergic or beta-adrenergic pathways in cysteamine-induced gastrin release at the level of the stomach and suggest that in vivo such autonomic effects are mediated extrinsically.


Transrectal ultrasonography in the diagnosis and staging of carcinoma of the prostate.
Transrectal prostatic ultrasonography is a potentially valuable means to evaluate the prostate of men with suspected carcinoma. We studied 118 patients with this modality before histological evaluation of the prostate (20 underwent radical prostatectomy, 75 core needle biopsy and aspiration cytology, and 23 transurethral resection of the prostate). Transrectal ultrasonography was more efficient than digital rectal examination in the staging of carcinoma of the prostate before radical prostatectomy. The value of transrectal ultrasonography in the diagnosis of prostatic cancer in men with an abnormal-feeling prostate on digital rectal examination is less certain, since 10 of 75 patients (13 per cent) in this group had a falsely positive scan. The predictive value of a scan positive for malignancy was 37 per cent. Further refinements in the technique of transrectal prostatic ultrasonography are needed to realize fully the diagnostic potential of this imaging modality.


Genetic and phenotypic variation and consistency in cow preference and circadian use of robotic milking units.
Many dairy herds use automatic milking stations (AMS), with cows in large herds often having access to 2 or more AMS, and must choose between them when they go for milking. Individual cows acquire routines of either consistently using a specific milking box or consistently using any available milking box. Here, we hypothesized that the degree of use of the same milking box was an expression of preference, and quantified it as preference consistency score (PCS). The PCS was calculated as a ratio between the excess frequencies of the first choice over the base frequency of "not first choice" over 15-d segments of lactation. This ratio was 0 if all choices were taken equally, and became 1.0 if only the first choice was taken in all events. We investigated the consistency of milking box preference in 2 cohorts (one Holstein and one Jersey) across 6 commercial dairy herds in Denmark (n = 4,665 cows total). In addition to PCS, we recorded and analyzed associated milking and behavior traits, including a time profile index showing use of specific clock hours when cows were milked (Time_profile, based on excess use of specific clock hours), milking frequency, time spent in the milking box, and milk yield. Records from each milking event were condensed into 15-d segments based on days in milk. The data were analyzed using a linear mixed model, with random genetic and individual cow effects, to estimate heritability (h2), repeatability (t), and individual level correlations (ri) between traits. The average PCS was 0.43 and 0.41 in Holstein and Jersey, respectively, showing that cows developed routines for consistently using the same milking box; however, some cows had lower preference (i.e., greater flexibility in use). The Time_profile indicated that some cows were milked in a few hour-bins, whereas others were more flexible. The PCS and Time_profile traits had low heritability (h2, PCS/Time_profile = 0.07 ± 0.02/0.11 ± 0.02 Holstein, 0.13 ± 0.03/0.04 ± 0.02 Jersey) and moderate repeatability (t, PCS/Time_profile = 0.47/0.40 Holstein, 0.50/0.42 Jersey). The 2 traits were weakly correlated with each other (ri = 0.18 and 0.17), and were weakly correlated with milk yield (ri range: 0.0 to -0.10). However, the time profile was strongly correlated with milking frequency (ri range: -0.81 to -0.73), and was moderately correlated with daily box time (ri range: -0.43 to -0.35). In general, Holstein and Jersey parameter estimates were of similar size, and thus in good agreement. Overall, individual cows covered a broad spectrum of preference consistency, both regarding the use of specific milking boxes and time profiles, with these 2 traits representing different aspects or dimensions of milking behavior. The findings that some cows have strong preferences for specific AMS may be most useful in herd management and farm design. The weak correlation to milk yield indicated that yield minimally affected these 2 milking associated behavior traits. In conclusion, although the traits were repeatable, heritability was low; thus, genetic selection for milk yield might minimally affect these 2 traits.


Metabolic changes during estivation in the common earthworm Aporrectodea caliginosa.
The common earthworm Aporrectodea caliginosa survives drought by forming estivation chambers in the topsoil under even very slight reductions in soil water activity. We induced estivation in a soil of a consistency that allowed the removal of intact soil estivation chambers containing a single worm. These estivation chambers were exposed to 97% relative humidity for 30 d to simulate the effect of a severe summer drought. Gas exchange, body fluid osmolality, water balance, urea, and alanine were quantified, and whole-body homogenates were screened for changes in small organic molecules via (1)H-nuclear magnetic resonance (NMR). Formation of estivation chambers was associated with a dramatic increase in body fluid osmolality, from 175 to 562 mOsm kg(-1), accompanied by a 20% increase in water content. Dehydration for 1 mo caused a further increase to 684 mOsm kg(-1), while the worms lost 50% of their water content. Gas exchange was depressed by 50% after worms entered estivation and by 80% after a further 30 d of dehydration. Urea concentrations increased from 0.3 to 1 micromol g(-1) dry mass during this time. Although (1)H-NMR did not provide the identity of the osmolytes responsible for the initial increase in osmolality after estivation, it showed that alanine increased to more than 80 mmol L(-1) in the long-term-estivation group. We propose that alanine functions as a nitrogen depot during dehydration and is not an anaerobe product in this case.


SemEHR: A general-purpose semantic search system to surface semantic data from clinical notes for tailored care, trial recruitment, and clinical research.
Unlocking the data contained within both structured and unstructured components of electronic health records (EHRs) has the potential to provide a step change in data available for secondary research use, generation of actionable medical insights, hospital management, and trial recruitment. To achieve this, we implemented SemEHR, an open source semantic search and analytics tool for EHRs. SemEHR implements a generic information extraction (IE) and retrieval infrastructure by identifying contextualized mentions of a wide range of biomedical concepts within EHRs. Natural language processing annotations are further assembled at the patient level and extended with EHR-specific knowledge to generate a timeline for each patient. The semantic data are serviced via ontology-based search and analytics interfaces. SemEHR has been deployed at a number of UK hospitals, including the Clinical Record Interactive Search, an anonymized replica of the EHR of the UK South London and Maudsley National Health Service Foundation Trust, one of Europe's largest providers of mental health services. In 2 Clinical Record Interactive Search-based studies, SemEHR achieved 93% (hepatitis C) and 99% (HIV) F-measure results in identifying true positive patients. At King's College Hospital in London, as part of the CogStack program (github.com/cogstack), SemEHR is being used to recruit patients into the UK Department of Health 100 000 Genomes Project (genomicsengland.co.uk). The validation study suggests that the tool can validate previously recruited cases and is very fast at searching phenotypes; time for recruitment criteria checking was reduced from days to minutes. Validated on open intensive care EHR data, Medical Information Mart for Intensive Care III, the vital signs extracted by SemEHR can achieve around 97% accuracy. Results from the multiple case studies demonstrate SemEHR's efficiency: weeks or months of work can be done within hours or minutes in some cases. SemEHR provides a more comprehensive view of patients, bringing in more and unexpected insight compared to study-oriented bespoke IE systems. SemEHR is open source, available at https://github.com/CogStack/SemEHR.


Respiratory syncytial virus infections and intravenous gamma-globulins.
The respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Throughout the world annual RSV epidemics result in numerous hospitalizations, substantial morbidity and some mortality. Until the recent introduction of ribavirin only supportive therapy has been available for treating these infections. The development of animal models of RSV infection and the observation that some lots of immunoglobulin prepared for intravenous administration contained substantial RSV-neutralization antibody titers, prompted a series of studies examining the safety and efficacy of immunoglobulin prepared for intravenous administration in the prophylaxis and treatment of RSV infections. This discussion will review our published, or soon to be published, studies on the use of Sandoglobulin for both immunoprophylaxis and immunotherapy of RSV infections in cotton rats. It will summarize studies utilizing both parenteral and topical (tracheal) Sandoglobulin therapy for RSV infections in owl monkeys. Finally the results of a small double blind trial of parenteral albumin or Sandoglobulin in the therapy of RSV bronchiolitis and/or pneumonia in hospitalized children will be reviewed. The data show that immunoprophylaxis and immunotherapy of RSV infections in laboratory animals was well-tolerated, was safe and induced highly significant reductions in RSV shedding from the lower respiratory tract. Further, immunotherapy of RSV infections in children was also well-tolerated, induced no short or long term evidence of toxicity or injury and caused significant improvements in oxygenation and reductions in RSV shed from the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)


A weight-loss program adapted to the menstrual cycle increases weight loss in healthy, overweight, premenopausal women: a 6-mo randomized controlled trial.
Hormonal fluctuations during the menstrual cycle influence energy intake and expenditure as well as eating preferences and behavior. We examined the effect in healthy, overweight, premenopausal women of a diet and exercise weight-loss program that was designed to target and moderate the effects of the menstrual cycle compared with the effect of simple energy restriction. A total of 60 healthy, overweight, premenopausal women were included in a 6-mo weight-loss program in which each subject consumed a diet of 1600 kcal/d. Subjects were randomly assigned to either a combined diet and exercise program that was tailored to metabolic changes of the menstrual cycle (Menstralean) or to undergo simple energy restriction (control). Thirty-one women (19 Menstralean and 12 control women) completed the study [mean ± SD body mass index (in kg/m(2)): 32.0 ± 5.2]. Both groups lost weight during the study. In an intention-to-treat analysis, the Menstralean group did not achieve a clinically significant weight loss compared with that of the control group (P = 0.61). In per-protocol analyses, a more-pronounced weight loss of 4.3 ± 1.4 kg (P = 0.002) was shown in adherent Menstralean subjects than in the control group. A differentiated diet and exercise program that is tailored to counteract food cravings and metabolic changes throughout the menstrual cycle may increase weight loss above that achieved with a traditional diet and exercise program in women who can comply with the program. This trial was registered at clinicaltrials.gov as NCT01622114.


[Functional results in the surgery of congenital cataract].
During 1983-1993, 202 patients (a total of 230 eyes), 113 males and 117 females, were operated. From these, 47 selected cases could not be properly followed and the functional results were established only after repeated checking. In these cases, the surgical techniques consisted of 7 cryoextractions, 47 extracapsular extractions and 18 irrigations-aspirations in double stream. 47 lens implants have been introduced, 43 were Fedorov [correction of Fyodorov]-type with pupillary fixation and 4 were posterior chamber implants. The visual acuity was almost the same to both the patients who have benefited from implants and to those corrected with contact lens or glasses.


Multigene Phylogenies of the Estuarine Sesarmid Parasesarma bidens Species Complex (Decapoda: Brachyura: Sesarmidae), with Description of Three New Species.
S Parasesarma bidens (De Haan, 1835) is a common intertidal sesarmid crab that inhabits the estuarine and mangrove regions of East Asia, as well as Vietnam and the Philippines. Previous studies have suggested that P. bidens is a species complex composed of several species. Our findings indicated that the P. bidens species complex is monophyletic with six clades, as shown by reconstructed phylogenies based on mitochondrial 16S rDNA and cytochrome c oxidase subunit I, as well as nuclear 28S rDNA. Specimens of each clade exhibited different characters, including the morphology of the cheliped, anterior carapace, male gonopod 1, and female vulvae, as well as the coloration. Three species in this complex have been previously described: P. bidens (De Haan, 1835), P. cricotum (Rahayu & Davie, 2002), and P. sanguimanus Li, Shih & Ng, 2019. Here, we describe three additional species: P. continentale n. sp., P. insulare n. sp., and P. chiahsiang n. sp. Biogeographically, the range of P. bidens includes the southern margin of Korea, the main islands of Japan, and the Ryukyus, with a comparatively northern distribution. P. continentale is widely distributed from the continental coasts of southeastern and southern China (including northern Hainan Island) to southern Vietnam and is occasionally found in Penghu, Taiwan. Parasesarma insulare is an insular species distributed from Taiwan main island, the central Philippines, to northern Borneo. Finally, P. chiahsiang is mainly limited to the Penghu Islands (Pescadores) but is also sometimes found in Taiwan main island and the offshore Gueishan Island.


[Planning and execution of a course in puericulture in an ambulatory service].
With a population of which 42.6% is under 14 years old, Brazil is especially in need of general practitioners with a good gourding in pediatrics. The fourth year of premedical training at the Botucatu Medical School at São Paulo, Brazil, includes a course in child care designed to help fill this need by giving the students their first contact with the problems of children. The course lasts 12 weeks and is given in the pediatric outpatient ward of the School's teaching hospital; its purpose is to accustom the student to dealing with members of the families of young patients while learning important aspects of clinical care at the early stages of his training, and using, in his contacts with patients, a vocabulary that the latter can understand. The course is designed to given the student not only theoretical knowledge, but also training for future practice, under the constant guidance of their instructors. A weekly evaluation of the progress of the course, in which the students participate, yields information for the ongoing improvement of the program, which has been conducted for almost ten years.


Clinical and Epidemiologic Description of Orofacial Clefts in Bogota and Cali, Colombia, 2001-2015.
Among congenital craniofacial anomalies, orofacial clefts (OFCs) are the most common. Global prevalence is 2 in 1000 and in Colombia, 1 in 700. Our goal was to describe cleft palate (CP) prevalence and cleft lip with or without cleft palate (CL±P) from 2001 to 2015 in Bogota and Cali, Colombia. Using the ECLAMC case-control design method, information was obtained from the Congenital Anomalies Monitoring and Surveillance Programs in Bogota and Cali. We describe the prevalence of cases classified into the following groups: isolated, polymalformed, and syndromic. The proportion of cases and controls was 1:4. Data were analyzed using frequency distribution and Student t test to compare means and 95% confidence intervals (CIs). We identified 529 OFC cases and 2116 controls from 448,930 births: a rate of 11.8 per 10,000 (CI = 10.80-12.83). From the total cases, 73% were identified with CL/CP compared to 27% with CP. Males had higher CL±P (59%) prevalence, whereas the highest neonatal mortality was observed among polymalformed cases (7%). The most common anomaly identified among our cases was cleft lip without isolated cleft palate (58%). We found that OFCs are linked to birthweight, size, and gestational age and higher parity with statistically significant differences in all variables compared to controls. OFC is a highly prevalent anomaly in Colombia, with a range of maternal and infant differences across case subgroups. The identification of important OFC subgroups that follow certain patterns of prevalence may prove useful to primary and tertiary care facilities with the goal of reducing further disability.


Bilateral Optic Disc Pits With Posterior Pituitary Ectopia.
Posterior pituitary ectopia has been reported previously in association with optic nerve hypoplasia, as a variant of septo-optic dysplasia. We describe a 14-year-old boy with posterior pituitary ectopia and bilateral optic disc pits. He had hypopituitarism and a reduction in visual acuity to 20/40 in each eye, owing to loss of foveal ganglion cells. Optic pits and posterior pituitary ectopia may have occurred together in the same subject by chance, but the rarity of both conditions suggests a possible association.


Efficacy of a large magnesium alloy rumen bolus in the prevention of hypomagnesemic tetany in cows.
Two cow-calf grazing studies and 2 rate-of-disappearance trials in steers surgically prepared with rumen fistula were conducted to evaluate the efficacy of a large Mg alloy rumen bolus in preventing hypomagnesemic tetany (grass tetany). The mineral composition of the forage and results of study of 2 cows in the cow-calf studies indicated that an environment conducive to the occurrence of grass tetany existed. Grass tetany occurred in a cow that was given a Mg bolus and in a control cow. Administration of 1 or 2 mg boluses did not affect blood serum Mg, Ca, P, and K concentrations. Bolus treatment did not affect cow-calf performance or conception rate. The rate of weight loss of the boluses in the surgically prepared steers (rumen fistula) ranged from 0.71 to 1.43 g/day or 0.66 to 1.33 g of Mg/day. Steer differences affected the rates of disappearance patterns of the boluses. The rate of disappearance was relatively constant over a 175-day period and regurgitation or passage was not a problem. Although administration of the boluses could have prevented tetany in some animals (borderline), the rate of Mg release appears too slow to be highly effective in preventing grass tetany.


Childhood Injury Prevention: Predictors of Home Hazards in Latino Families Enrolled in SafeCare®.
This archival project (a) examined potential risk and protective factors for hazards in the homes of Spanish-speaking immigrant Latino families and (b) provided an independent examination of the SafeCare®+ Home Safety module adapted for Latino families at high risk for child neglect. The sample comprised 92 Latina caregivers of young children enrolled in SafeCare®+. Results of the negative binomial regression model of predictors of home hazards before the Home Safety module found none of the factors were significant. The longitudinal analysis with a negative binomial model found significant effects both during (b = -0.905, p < .001) and after (b = -2.118, p < .001) the intervention. Depression was negatively associated with the number of hazards (b = -0.026, p < .05, β = -.1858). Support for application of SafeCare®+ Home Safety module to prevent access to hazards for Latino children was found.


Costs of injuries and ill health in the workplace in South Korea.
Industrial accidents affect the sustainable development of any country, enterprise or individual. This study estimated the costs of loss due to industrial accidents in South Korea in 2013, based on the 4th Korean Working Conditions Survey. The total costs of loss were estimated at USD 27,224 million, with individuals losing the most at 79.5%, followed by employers at 20.4% and the government at 0.1%. These costs were equivalent to 2.1% of South Korea's gross domestic product in 2013. The costs to society/death due to industrial accidents were USD 640,000; USD 7000/individual out of work for ≤3 days and USD 242,000/individual out of work for ≥4 days. These costs make it easy to calculate losses incurred due to industrial accidents. Costs of loss can also be used by the government as basic data to establish industrial safety and health policies.


Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer.
A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.


Pharmacological evaluation of early afterdepolarisations induced by sea anemone toxin (ATXII) in dog heart.
ATXII is a polypeptide toxin isolated from the sea anemone, Anemonia sulcata, known to delay sodium inactivation markedly and to induce early afterdepolarisations. The aim was to investigate the mechanism of its action. The mechanism of ATXII induced early afterdepolarisations was investigated in vitro in canine endocardial preparations using standard microelectrode techniques. ATXII (2 x 10(-7) M) induced cycle length dependent prolongation of plateau, more marked in Purkinje than in muscle fibres, and early afterdepolarisations in Purkinje fibres only. The calcium channel antagonists verapamil (10(-6) M, 10(-5) M) and cobalt (2-4 mM), and drugs that block calcium release from the sarcoplasmic reticulum, ryanodine (10(-6) M, 10(-5) M) and caffeine (10 mM), did not antagonise the ATXII effects. However, tetrodotoxin (5 x 10(-6) M) and lignocaine (4 x 10(-5) M) shortened the action potential and suppressed early afterdepolarisations. The effects of lignocaine were seen at concentrations that did not significantly affect Vmax. ATXII induced early after depolarisations are due to the effects of ATXII on Na+ entry, probably via a slowly inactivated Na+ channel population. Calcium entry through the sarcolemmal Ca2+ channels and cyclic Ca2+ release from the sarcoplasmic reticulum are not required for the genesis of early afterdepolarisations in this model.


Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus.
We examined synaptic plasticity in the dentate gyrus (DG) of the hippocampus in vitro in juvenile C57Bl6 mice (28-40 days of age), housed in control conditions with minimal enrichment (Controls) or with access to an exercise wheel (Runners). LTP expression was significantly greater in slices from Runners than in those from Controls, but could be blocked by APV in both groups. LTP was significantly reduced by NR2B subunit antagonists in both groups. NVP-AAM077, an antagonist with a higher preference for NR2A subunits over NR2B subunits, blocked LTP in slices from Runners and produced a slight depression in Control animals. LTD in the DG was also blocked by APV, but not by either of the NR2B specific antagonists. Strikingly, NVP-AAM077 prevented LTD in Runners, but not in Control animals, suggesting an increased involvement of NR2A subunits in LTD in animals that exercise. NVP-AAM077 did not block LTD in NR2A Knock Out (KO) animals that exercised, as expected. In an attempt to discern whether NMDA receptors located at extrasynaptic sites could play a role in the induction of LTD, DL-TBOA was used to block excitatory amino acid transport and increase extracellular glutamate levels. Under these conditions, LTD was not blocked by the co-application of a specific NR2B subunit antagonist in either group, but NVP-AAM077 again blocked LTD selectively in Runners. These results indicate that NR2A and NR2B subunits play a significant role in LTP in the DG, and that exercise can significantly alter the contribution of NMDA NR2A subunits to LTD.


High bone density due to a mutation in LDL-receptor-related protein 5.
Osteoporosis is a major public health problem of largely unknown cause. Loss-of-function mutations in the gene for low-density lipoprotein receptor-related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis-pseudoglioma. We performed genetic and biochemical analyses of a kindred with an autosomal dominant syndrome characterized by high bone density, a wide and deep mandible, and torus palatinus. Genetic analysis revealed linkage of the syndrome to chromosome 11q12-13 (odds of linkage, >1 million to 1), an interval that contains LRP5. Affected members of the kindred had a mutation in this gene, with valine substituted for glycine at codon 171 (LRP5V171). This mutation segregated with the trait in the family and was absent in control subjects. The normal glycine lies in a so-called propeller motif that is highly conserved from fruit flies to humans. Markers of bone resorption were normal in the affected subjects, whereas markers of bone formation such as osteocalcin were markedly elevated. Levels of fibronectin, a known target of signaling by Wnt, a developmental protein, were also elevated. In vitro studies showed that the normal inhibition of Wnt signaling by another protein, Dickkopf-1 (Dkk-1), was defective in the presence of LRP5V171 and that this resulted in increased signaling due to unopposed Wnt activity. The LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass and point to Dkk as a potential target for the prevention or treatment of osteoporosis.


Longterm Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases.
The protection duration of herpes zoster (HZ) vaccination is unclear among patients with autoimmune (AI) diseases. Using 2006-2013 Medicare data, HZ vaccinated patients with AI were matched 1:2 to unvaccinated HZ. Incidence rates (IR) and adjusted risk ratios over time were calculated using Poisson regression. Of 59,627 vaccinated patients, crude IR increased from 0.75/100 person-years during the first year post-vaccination to 1.25 during the seventh year. Vaccinated patients had a significantly lower risk of HZ compared with the unvaccinated through 5 years. HZ vaccination was significantly protective only for about 5 years among patients with AI.


Playing it close to the VEST and the clinical guidelines: Clinical guideline compliance in HFrEF patients-Role of WCD.
Guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) has been challenging to achieve universally. Healthcare providers who seek to achieve optimal medical therapy frequently consider either a wearable cardioverter defibrillator (WCD) or an implantable cardioverter defibrillator (ICD) as indicated. The dynamic process of communication and physician recommendations marks a setting to study the relative interdependence of medical therapies and best practice. The purpose of this study was to examine the long-term impact of the WCD on GDMT. We hypothesized the WCD serves as a "gateway" therapy, likely impacting other optimal strategies such that successful use of WCD improves GDMT adherence. Electronic medical records (EPIC) were manually reviewed to extract data elements in this observational study of 1289 HFrEF patients from 2013-2015. Data included demographics, comorbidities, and use of GDMT including an ICD use in persistently low ejection fraction (≤36%) patients after 90 days. WCD use was significantly associated with prescribing adherence to GDMT, χ2 (1, N = 981) = 33.36, P < 0.001. Further, WCD use was significantly associated with recommendations for follow-up echocardiographic study, χ2 (1, N = 865) = 66.94, P < 0.001 and use of primary prevention ICD, χ2 (1, N = 1093) = 19.00, P < 0.001. This study demonstrates the use of the WCD correlates with improved clinician use of GDMT, follow-up echocardiographic studies, and appropriate use of primary prevention ICD. Thus, the potential benefits of the WCD and its care processes may extend beyond prevention of sudden cardiac death to enhanced optimization of GDMT.


Neonatal lines in the enamel of primary teeth--a morphological and scanning electron microscopic investigation.
The neonatal line (NNL) is in principle found in all primary teeth and the line represents the time of birth. Earlier findings of the appearance of the NNL in light microscope and in microradiographs have shown not only changes in the prism direction of the enamel, but that the NNL has a hypomineralized character. The neonatal line was analyzed in un-decalcified sections of primary lower and central incisors, collected from individuals of different ages utilizing polarized light microscopy, microradiography, scanning electron microscopy (SEM) and X-ray analysis (XRMA). In polarized light the NNL appeared to have a more porous structure than the enamel in general. The appearance of the NNL as a dark line in microradiographs is interpreted as the NNL being less mineralized than neighbouring enamel. Analysis with ImageJ visualized the reduction of the amount of grey value, indicating that the NNL is less mineralized. Analysis of the NNL in SEM showed a reduction of the diameter of enamel prisms, the more narrow diameters continued through the postnatal enamel. A change of the growth direction of the prisms was also observed at the NNL. In a three-dimensional image the NNL appeared as a grove, however, in non-etched enamel no grove was seen. The elemental analyses with XRMA showed no marked changes in the content of C, Ca, P, N, O or S in the area around the NNL. The NNL is an optical phenomenon due to alterations in height, and degree of mineralization of the enamel prisms.


Laparoscopic transabdominal cerclage: Outcomes of 121 pregnancies.
Cervical insufficiency is a significant cause of morbidity and mortality. Cervical cerclage is one option in the management of cervical insufficiency. To evaluate obstetric outcomes following insertion of a pre-pregnancy laparoscopic transabdominal cerclage in women at high risk for pre-term labour and/or mid-trimester pregnancy loss. A prospective observational study of consecutive women who underwent laparoscopic transabdominal cerclage from 2007 to 2017. Eligible women had a diagnosis of cervical insufficiency based on previous obstetric history and/or a short or absent cervix and were considered not suitable for a transvaginal cerclage. The primary outcome was neonatal survival and the secondary outcome was delivery of an infant at ≥34 weeks gestation. Surgical morbidity and complications were also evaluated. During the study period, 225 women underwent laparoscopic transabdominal cerclage. We present the outcomes of 121 pregnancies resulting in 125 babies. The perinatal survival rate of viable pregnancies was 98.5% with a mean gestational age at delivery of 35.2 weeks; 79.7% of babies were delivered at ≥34.0 weeks gestation. Laparoscopic transabdominal cerclage is a safe and effective procedure resulting in favourable obstetric outcomes in women with a poor obstetric history. For optimal success the procedure requires the correct surgical expertise, equipment and appropriate patient selection.


Assessing the factor structure of the Chinese conformity to masculine norms inventory.
The purpose of the present study was to examine the factor structure and assess the reliability of the Chinese Conformity to Masculine Norms Inventory-46 (CCMNI-46). Using a cohort of 254 Hong Kong-born Chinese males, scale reliability determination involved the internal consistencies of the entire instrument. Ages of respondents ranged from 18 to 81 years (M = 38.05; SD = 17.3). Confirmatory factor analysis provided support for the psychometric properties of the CCMNI-46, thus confirming the multidimensional structure of the CMNI-46 and the replicability of the CMNI using a Hong Kong Chinese sample. All items loaded onto the corresponding factor with the exception of one item from the emotional control subscale. The overall reliability of the CCMNI-46 was lower than previous Western studies and may well reflect the subtle diversity of masculinity across cultures. The findings offered psychometric support for use of the CCMNI-46 in research and practice regarding Hong Kong Chinese masculinity. The CCMNI-46 provides a useful template for the operationalization of masculine norms in Chinese society.


The Burden of Congenital Cytomegalovirus Infection: A Prospective Cohort Study of 20 000 Infants in Finland.
Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and causes significant morbidity. This study was undertaken to evaluate the benefits of screening newborns for cCMV and to understand the cCMV disease burden in Finland. Infants born in Helsinki area hospitals were screened for CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants and matched controls were monitored to determine their neurodevelopmental, audiological, and ophthalmological outcomes at 18 months of age. Griffiths Mental Development Scales, otoacoustic emission and sound field audiometry, and ophthalmologic examination were performed. Of the 19868 infants screened, 40 had confirmed cCMV infection (prevalence, 2 in 1000 [95% confidence interval, 1.4-2.6 in 1000]). Four (10%) infants had symptomatic cCMV. Griffiths general quotients did not differ significantly between the CMV-positive (mean, 101.0) and control (mean, 101.6) infants (P = .557), nor did quotients for any of the Griffiths subscales (locomotion, personal-social, hearing and language, eye and hand, performance) (P = .173-.721). Four of 54 CMV-positive ears and 6 of 80 CMV-negative ears failed otoacoustic emission testing (P = 1.000). The mean minimal response levels over the frequencies 500 Hz to 4 kHz in the sound field audiometry did not differ between CMV-positive (mean, 34.31-dB hearing level) and control (mean, 32.73-dB hearing level) infants (P = .338). No CMV-related ophthalmologic findings were observed. The prevalence of cCMV was low, and outcomes at 18 months of age did not differ between the infected infants and healthy control infants. With such a low burden in Finland, universal newborn screening for cCMV seems unwarranted.


Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment.
A new group of compounds, promising for the design of original multitarget therapeutic agents for treating neurodegenerative diseases, based on conjugates of aminoadamantane and carbazole derivatives was synthesized and investigated. Compounds of these series were found to interact with a group of targets that play an important role in the development of this type of diseases. First of all, these compounds selectively inhibit butyrylcholinesterase, block NMDA receptors containing NR2B subunits while maintaining the properties of MK-801 binding site blockers, exert microtubules stabilizing properties, and possess the ability to protect nerve cells from death at the calcium overload conditions. The leading compound C-2h has been shown the most promising effects on all analyzed parameters. Thus, these compounds can be regarded as promising candidates for the design of multi-target disease-modifying drugs for treatment of AD and/or similar neuropathologies.


A Degenerative Form of Mixed Transcortical Aphasia.
Mixed transcortical aphasia (MTA) is characterized by decreased spontaneous speech, impaired naming, and poor comprehension, but with intact repetition. MTA has been reported to be the sequela of left hemisphere watershed infarction that isolates Wernicke's perisylvian arc. We report a 55-year-old right-handed woman who began having word-finding difficulty and then gradually developed impaired spontaneous speech, comprehension, and naming, but with intact repetition. Magnetic resonance imaging showed atrophy in the left frontal, parietal, and temporal lobes. This patient demonstrates that MTA can occur as a result of neurodegenerative disease. Further research is needed to learn whether progressive MTA is a late stage of primary progressive aphasia, examine the neuropathology associated with this syndrome, and identify treatment strategies.


Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase.
An understanding of how conformational dynamics modulates function and catalysis of human monoacylglycerol lipase (hMGL), an important pharmaceutical target, can facilitate the development of novel ligands with potential therapeutic value. Here, we report the discovery and characterization of an allosteric, regulatory hMGL site comprised of residues Trp-289 and Leu-232 that reside over 18 Å away from the catalytic triad. These residues were identified as critical mediators of long-range communication and as important contributors to the integrity of the hMGL structure. Nonconservative replacements of Trp-289 or Leu-232 triggered concerted motions of structurally distinct regions with a significant conformational shift toward inactive states and dramatic loss in catalytic efficiency of the enzyme. Using a multimethod approach, we show that the dynamically relevant Trp-289 and Leu-232 residues serve as communication hubs within an allosteric protein network that controls signal propagation to the active site, and thus, regulates active-inactive interconversion of hMGL. Our findings provide new insights into the mechanism of allosteric regulation of lipase activity, in general, and may provide alternative drug design possibilities.


[Association between depression and fall risk among elderly community residents].
To investigate the relationship between depression and fall risk in the elderly. Residents of a village in Kumamoto Prefecture, Japan (563 people), aged ≥65 years were given a self-administered questionnaire survey between June and July 2010. To evaluate depression status and fall risk, the Geriatric Depression Scale--Short Form and the Simple Screening Test for Risk of Falls were administered. Adjustment factors assessed were age, sex, medical history for diseases associated with falls, usage of hypnotics, and cognitive dysfunction. We examined the relationship between depression and fall risk using multiple logistic regression analysis. Given that some degree of correlation was expected among adjustment factors in the model, we constructed a model that introduced the adjustment factors stepwise to confirm the robustness of the model and any effect of multicollinearity. Overall (n=395), after excluding data from participants with significant cognitive disturbance or severe physical problems from among valid responders, a significant relationship was found between depression and fall risk in all models. The odds ratio was 2.28 (95% confidence interval: 1.31-3.96) in the final model, controlling for all adjustment factors. Our findings suggest a significant relationship between depression and fall risk in the elderly. This relationship implies that the improvement of depression could be an effective measure to decrease fall risk in the elderly.


A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats.
The brain is still maturing during adolescence and interfering with such a vulnerable period may lead to structural and functional consequences. We investigated the effect of a single cocaine exposure on dendritic spine structure and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats 7 days after a single cocaine administration. We found a reduced number of dendritic spines, suggesting that cocaine lowers the density of dendritic spines in the mPFC of adolescent rats. Since dendritic spines are postsynaptic glutamatergic protrusions, we investigated the main determinants of glutamate postsynaptic responsiveness. In the postsynaptic density, cocaine reduced the expression of the NMDA receptor subunits GluN1, GluN2A and GluN2B as well as of the AMPA GluA1 and GluA2 subunits. Cocaine also impaired their synaptic stability since the expression of the scaffolding proteins SAP102 and SAP97, critical for the anchoring of such receptors at the postsynaptic membrane, was reduced as well. The expression of PSD-95 and Arc/Arg3.1, which play structural and functional roles in glutamate neurons, was also similarly reduced. Such changes were not found in the whole homogenate, ruling out a translational effect of cocaine and implying, rather, an impaired synaptic retention at the active zones of the synapse. Notably, neither these critical glutamate determinants nor the density and morphology of the dendritic spines were altered in the mPFC of adult animals, suggesting that a single cocaine exposure selectively impairs the developmental trajectory of the glutamate synapse. These results indicate a dynamic impairment of mPFC glutamate homeostasis during a critical developmental window that persists for at least one week after a single cocaine administration. Our results identify dysfunctional glutamate synapse as a major contributor to the mechanisms that distinguish adolescent vs. adult outcomes of a single cocaine exposure.


The impact of local immigration enforcement policies on the health of immigrant hispanics/latinos in the United States.
We sought to understand how local immigration enforcement policies affect the utilization of health services among immigrant Hispanics/Latinos in North Carolina. In 2012, we analyzed vital records data to determine whether local implementation of section 287(g) of the Immigration and Nationality Act and the Secure Communities program, which authorizes local law enforcement agencies to enforce federal immigration laws, affected the prenatal care utilization of Hispanics/Latinas. We also conducted 6 focus groups and 17 interviews with Hispanic/Latino persons across North Carolina to explore the impact of immigration policies on their utilization of health services. We found no significant differences in utilization of prenatal care before and after implementation of section 287(g), but we did find that, in individual-level analysis, Hispanic/Latina mothers sought prenatal care later and had inadequate care when compared with non-Hispanic/Latina mothers. Participants reported profound mistrust of health services, avoiding health services, and sacrificing their health and the health of their family members. Fear of immigration enforcement policies is generalized across counties. Interventions are needed to increase immigrant Hispanics/Latinos' understanding of their rights and eligibility to utilize health services. Policy-level initiatives are also needed (e.g., driver's licenses) to help undocumented persons access and utilize these services.


Time-gated cell imaging using long lifetime near-infrared-emitting quantum dots for autofluorescence rejection.
Fluorescence imaging is a promising technique for the detection of individual cell migration. Its sensitivity is, however, limited by a high tissue autofluorescence and a poor visible light penetration depth. In order to solve this problem, the fluorescence signal peak wavelength should lie in an absorption and diffusion free region and should be distinguishable, either spectrally or temporally, from the autofluorescence background. We present, here, the synthesis and characterization of low toxicity Zn-Cu-In-Se/ZnS core/shell quantum dots. Their fluorescence emission wavelength peaks around 800 nm, where the absorption and scattering of tissues are minimal. They are coated with a new ligand, which yields small, stable, and bright individual probes in the live cell cytoplasm, even 48 h after the labeling. Furthermore, these near-infrared-emitting quantum dots have a long fluorescence lifetime component (around 150 ns) compared to autofluorescence (<5 ns). Taking the advantage of this property and coupling these probes to a time-gated detection, we demonstrate efficiently the discrimination between the signal and short lifetime fluorescence such as the autofluorescence. This technique is supported by a method we developed, to massively stain cells that preserves the quantum dot stability and brightness for 48 h.


Correctional nursing in Liguria, Italy: examining the ethical challenges.
Correctional nursing can involve significant ethical difficulties. This study examined ethical challenges encountered by correctional nurses in the Italian region of Liguria. Empirical data were analyzed in relation to relevant ethical standards. The former involved a study of 75 nurses and managers in the Ligurian correctional system, while the latter involved an analysis of the Italian Code of Ethics for Nurses and related standards for correctional practice. Quantitative and qualitative methods were used for the empirical study. Questionnaires were administered to collect data on participants' characteristics and care settings. The Measure of Job Satisfaction (MJS) was also administered. Five focus groups were conducted. Quantitative Data: Respondents identified factors that mostly impacted on recruitment and retention. Unfavourable factors included: structural, organizational, and relational factors. Favourable factors included: nursing consultation, continuing education activities, and peer support. MJS results were equal to 'unsatisfied'. Qualitative Data: five themes were identified through thematic analysis of focus group data: Health needs of incarcerated persons; Negotiation of the boundaries between care and custody; Job satisfaction related to nursing in a correctional setting; Barriers to providing good care; and Security needs. Ten categories of norms were identified in the Code as areas of ethical standards relevant for the empirical data. Our empirical findings demonstrate that these nursing standards can be systematically compromised in correctional settings. Nurses feel compelled to provide ethically-problematic nursing services, with situations of moral distress. This research informs the development of needed policy, educational, and practice changes for nurses in correctional settings.


[Hydatid cyst of soft tissues. Radiological aspects].
Hydatid disease of the soft tissues is rare, with a frequency between 2.4 and 5.3% of all sites of hydatid disease. We report a retrospective study of 6 cases of hydatid cyst of soft tissues. The mean age of our patients was 36 years (range: 25 and 63 years) and the sex-ratio was 5 females to 1 male. The clinical symptoms consisted in a mass which had been present for a mean of 12 months. Plain X-rays showed a water density mass with no associated bone lesions. Ultrasonography and computed tomography defined the features of the hydatid cysts, which were situated in muscle in 5 cases and in the subcutaneous tissue in 1 case. Their dimensions varied between 1.5 and 25 cm. All types of Gharbi's classification were observed. Secondary hydatid cysts outside of the soft tissues were observed in 2 patients. Medical imaging, essentially ultrasonography, was suggestive of the diagnosis. Computed tomography provided more precise information concerning the number, site and morphology of the lesions and was able to eliminate neoplastic disease.


Strengite dissolution in flooded soils and sediments.
Strengite (FePO(4) . 2H(2)O) undergoes partial dissolution under the reducing conditions existing in a flooded soil. The greatest release of phosphate and iron occurs under conditions of low oxidation-reduction potential in combination with low pH.


Diagnostic validity of helical CT compared to ultrasonography in renal-ureteral colic.
Helical CT without contrast is currently being evaluated for the diagnosis of renoureteral colic. Ureteral obstruction and other pathologies with similar symptoms can be rapidly identified. This study intends to evaluate the validity of CTh for these patients and to compare it with the ultrasound technique in order to consider the CTh as an efficient diagnostic alternative for these pathologies. A diagnostic evaluation study was carried out between January 2004 and December 2006 in patients with persistent renoureteral colic after standard care. They were blindly evaluated by ultrasound and CTh, maintaining the follow up until the "gold standard" confirmation. Qualitative variables were described by frequency and 95%CI and quantitative variables by position and dispersion measures. The Chi2 test was used to compare qualitative variables. Validity indicators and 95% CI were calculated and compared with McNemar test. 124 patients were studied. Lithiasis and the other diagnosis had frequencies of 59.7% and 40.3% respectively. The percentage of lithiasis obtained by ultrasound (92) was 22.8% and by CTh (124) was 59.7%. Validity indicators for CTh were superior to 95%, with 100% sensitivity and positive predictive value. Ultrasound specificity and positive predictive value were 100%, but sensitivity was only 29.6% (p<0.05). CTh can be considered a good alternative diagnostic technique in the renoureteral colic management.


Proteogenomic analysis of human colon carcinoma cell lines LIM1215, LIM1899, and LIM2405.
As part of the genome-wide and chromosome-centric human proteomic project (C-HPP), we have integrated shotgun proteomics approach and a genome-wide transcriptomic approach (RNA-Seq) of a set of human colon cancer cell lines (LIM1215, LIM1899 and LIM2405) that were selected to represent a wide range of pathological states of colorectal cancer. The combination of a standard proteomics approach (1D-gel electrophoresis coupled to LC/ion trap mass spectrometry) and RNA-Seq allowed us to exploit the greater depth of the transcriptomics measurement (∼ 9800 transcripts per cell line) versus the protein observations (∼ 1900 protein identifications per cell line). Conversely, the proteomics data were helpful in identifying both cancer associated proteins with differential expression patterns as well as protein networks and pathways which appear to be deregulated in these cell lines. Examples of potential markers include mortalin, nucleophosmin, ezrin, LASP1, alpha and beta forms of spectrin, exportin, the carcinoembryonic antigen family, EGFR and MET. Interaction analyses identified the large intermediate filament family, the protein folding network and adapter proteins in focal adhesion networks, which included the CDC42 and RHOA signaling pathways that may have potential for identifying phenotypic states representing poorly and moderately differentiated states of CRC, with or without metastases.


Simultaneous detection of antibodies to five Actinobacillus pleuropneumoniae serovars using bead-based multiplex analysis.
We developed and made a preliminary validation of a bead-based multiplexed immunoassay for simultaneous detection of porcine serum antibodies to Actinobacillus pleuropneumoniae serovars 1, 2, 6, 7, and 12. Magnetic fluorescent beads were coupled with A. pleuropneumoniae antigens and tested with a panel of serum samples from experimentally infected pigs and with serum samples from uninfected and naturally infected pigs. The multiplex assay was compared to in-house ELISAs and complement fixation (CF) tests, which have been used for decades as tools for herd classification in the Danish Specific Pathogen Free system. Assay specificities and sensitivities as well as the corresponding cutoff values were determined using receiver operating characteristic (ROC) curve analysis, and the A. pleuropneumoniae multiplex assay showed good correlation with the in-house ELISAs and CF tests with areas under ROC curves ≥ 0.988. Benefits of multiplexed assays compared to ELISAs and CF tests include reduced serum sample volumes needed for analysis, less labor, and shorter assay time.


Neural competition as a developmental process: early hemispheric specialization for word processing delays specialization for face processing.
Little is known about the impact of learning to read on early neural development for word processing and its collateral effects on neural development in non-word domains. Here, we examined the effect of early exposure to reading on neural responses to both word and face processing in preschool children with the use of the Event Related Potential (ERP) methodology. We specifically linked children's reading experience (indexed by their sight vocabulary) to two major neural markers: the amplitude differences between the left and right N170 on the bilateral posterior scalp sites and the hemispheric spectrum power differences in the γ band on the same scalp sites. The results showed that the left-lateralization of both the word N170 and the spectrum power in the γ band were significantly positively related to vocabulary. In contrast, vocabulary and the word left-lateralization both had a strong negative direct effect on the face right-lateralization. Also, vocabulary negatively correlated with the right-lateralized face spectrum power in the γ band even after the effects of age and the word spectrum power were partialled out. The present study provides direct evidence regarding the role of reading experience in the neural specialization of word and face processing above and beyond the effect of maturation. The present findings taken together suggest that the neural development of visual word processing competes with that of face processing before the process of neural specialization has been consolidated.


Comparative analysis of microbial communities during enrichment and isolation of DDT-degrading bacteria by culture-dependent and -independent methods.
Microcosms for enrichment of DDT degrading microorganisms were monitored using culture-dependent and -independent methods. Culture dependent methods isolated several strains with DDT degradation potential, Pseudomonas species being the most frequent. One isolate, Streptomyces sp. strain D3, had a degradation rate of 77% with 20mgL-1 of DDT after 7days incubation, D3 also had degradation rates of 75% and 30% for PCB77 (3,3',4,4'-tetrachloro biphenyl) and PCNB (pentachloronitrobenzene) respectively. Culture-independent high-throughput sequencing identified a different subset of the microbial community within the enrichment microcosms to the culture dependent method. Pseudomonas, the most frequently isolated strain, only represented the 12th most abundant operational taxonomic unit in the sequencing dataset (relative abundance 0.9%). The most frequently observed bacterial genus in the culture-independent analysis did not correspond with those recovered by culture-dependent methods. These results suggested that deep sequencing followed by a targeted isolation approach might provide an advantageous route to bioremediation studies.


Enhanced TCR-induced apoptosis in interferon regulatory factor 4-deficient CD4(+) Th cells.
Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4(+) T helper (Th) cells lacking IRF4 (IRF4(-/-)) are highly sensitive to apoptosis. After infection of IRF4(-/-) mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4(-/-) CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4(+) cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4(-/-) and IRF4(+/+) cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+) cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central in protecting CD4(+) cells against proapoptotic stimuli.


Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate in African-American Patients With Heart Failure.
This study sought to evaluate the effectiveness of hydralazine-isosorbide dinitrate (H-ISDN) in African Americans with heart failure (HF) with reduced ejection fraction (HFrEF). Among African-American patients with HFrEF, H-ISDN was found to improve quality of life and lower HF-related hospitalization and mortality rates in the A-HEFT (African-American Heart Failure Trial). Few studies have evaluated the effectiveness of this therapy in clinical practice. Veterans Affairs patients with a hospital admission for HF between 2007 and 2013 were screened. Inclusion criteria included African-American race, left ventricular ejection fraction <40%, and receipt of Veterans Affairs medications. Exclusions were documented contraindications to H-ISDN, creatinine >2.0 mg/dl, or intolerance to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Adjusted hazard ratios were calculated for patients who received H-ISDN 6-months before admission compared with patients who did not receive H-ISDN, by using inverse probability weighting of propensity scores and a time to death analysis for 18 months of follow-up. Propensity scores were generated using patients' characteristics, left ventricular ejection fraction, laboratory values, and hospital characteristics. The final cohort included 5,168 African-American patients with HF (mean age 65.2 years), with 15.2% treated with H-ISDN before index admission. After 18 months, there were 1,275 reported deaths (24.7%). The adjusted mortality rate at 18 months was 22.1% for patients receiving H-ISDN treatment and 25.2% for untreated patients (p = 0.009); adjusted hazard ratio: 0.85 (95% confidence interval: 0.73 to 1.00; p = 0.057). H-ISDN remains underused in African-American patients with HFrEF. In this cohort, the study found that H-ISDN use was associated with lower mortality rates in African-American patients with HFrEF when controlling for patient selection by using an inverse probability weighting of propensity scores.


OCULAR TOXICITY AFTER INADVERTENT INTRACAMERAL INJECTION OF HIGH DOSE OF CEFUROXIME DURING CATARACT SURGERY: A CASE SERIES.
To report ocular side effects after inadvertent intracameral injection of a high dose of cefuroxime. Nineteen eyes of 19 patients were seen in our eye department 1 week after the referring surgeon had injected an erroneous dose of intracameral cefuroxime (12.5 mg/0.1 mL in 14 patients, Group A, and 10 mg/0.1 mL in 5 patients, Group B) at the end of a cataract surgery. A complete ophthalmic examination was performed postoperatively. Eight patients (42.10%) exhibited ocular side effects. One patient (Group A) developed a noninfectious panuveitis. One case (Group B) had a serous macular detachment. Five patients (4 from Group A and 1 from Group B) showed a disruption of the ellipsoid layer with temporary/permanent drop in visual acuity. One patient presented with color alteration (Group A), but electrodiagnostic studies did not reveal any significant alterations. Anterior and posterior inflammation has been described after intracameral injection of high dose of cefuroxime. In this study, 10 mg to 12.5 mg of intracameral cefuroxime is shown to be, principally, toxic to the retina with transient or permanent retinal changes on optical coherence tomography which correlate with visual outcomes postoperatively. Protocols to avoid dilution errors should be available in theaters during cataract surgery where such commercial preparations are not available.


The effect of intravenous ranitidine on the intragastric pH of preterm infants receiving dexamethasone.
Gastric perforation is a catastrophic, albeit uncommon, side effect of steroid treatment for premature infants with bronchopulmonary dysplasia (BPD). A reduction of intragastric acidity may protect against peptic ulceration. The effect of different doses of ranitidine, given as intravenous infusions, on intragastric acidity in premature neonates was therefore examined. Ten consecutive, enterally starved, infants receiving dexamethasone (0.6 mg/kg) for BPD were enrolled. Intragastric pH was continuously monitored on the day before steroid treatment and on the four following days, initially without H2 blockade and then using a continuous intravenous infusion of ranitidine at 0.031, 0.0625, and 0.125 mg/kg/hour. An infusion of 0.0625 mg/kg/hour of ranitidine was sufficient to increase and maintain gastric pH above 4; the authors therefore use this infusion during dexamethasone administration as possible prevention of gastric perforation.


Energy and Nutrient Intakes: Findings from the Malaysian Adult Nutrition Survey (MANS).
Nutrition surveys based on a representative sample of the Malaysian adult population have hitherto not been reported. In 2003, the Ministry of Health, Malaysia, conducted the Malaysian Adult Nutrition Survey (MANS), the first and largest nutrition survey in the country which aimed to provide detailed quantitative information on nutritional status, food and nutrient intakes, and physical activity pattern on a nationwide representative sample of adult subjects between the ages of 18 and 59 years. The survey covered four zones in Peninsular Malaysia (Central, Southern, Northern and East Coast), Sabah and Sarawak. This paper presents the mean and selected percentiles of energy and nutrient intake of 6886 subjects by selected demographic and socioeconomic characteristics. Energy contributions by macronutrients and dietary adequacy in relation to the Recommended Nutrient Intake for Malaysians are also described. Information on dietary intake was collected by trained nutritionists using a one day 24-hour diet recall. Dietary data were analysed using Nutritionist Pro, a diet analysis software and statistical analysis was carried out using the SPSS ver. 13.0. In most of the demographic and socioeconomic groups, males had higher mean energy (1776 kcal) and nutrient intake and percent achievement of RNI than females (1447 kcal). The proportions of calories derived from macronutrients were within the recommendations for a healthy diet. Intake of micronutrients such as iron, calcium and vitamin A was about 50% of RNI particularly in women. Sodium intake of Malaysians, not reported in earlier studies, is also made available. Under-reporting using the EI/BMR ratio was found in half of the population studied. The present study provides the first national estimates of energy and nutrient intake of the Malaysian adult population. Regular nutrition surveys are needed at the national level to provide valuable information on trends in food and nutrient intake, particularly among age and ethnically diverse subgroups of the population.


Theory of magnetic reconnection in solar and astrophysical plasmas.
Magnetic reconnection is a fundamental process in a plasma that facilitates the release of energy stored in the magnetic field by permitting a change in the magnetic topology. In this paper, we present a review of the current state of understanding of magnetic reconnection. We discuss theoretical results regarding the formation of current sheets in complex three-dimensional magnetic fields and describe the fundamental differences between reconnection in two and three dimensions. We go on to outline recent developments in modelling of reconnection with kinetic theory, as well as in the magnetohydrodynamic framework where a number of new three-dimensional reconnection regimes have been identified. We discuss evidence from observations and simulations of Solar System plasmas that support this theory and summarize some prominent locations in which this new reconnection theory is relevant in astrophysical plasmas.


Integration of palliative care in chronic critical illness management.
Palliative care is an essential component of comprehensive care for all patients with chronic critical illness, including those receiving restorative or life-sustaining therapies. Core elements include alleviation of symptom distress, communication about care goals, alignment of treatment with the patient's values and preferences, transitional planning, and family support. Here we address strategies for assessment and management of symptoms, including pain, dyspnea, and depression, and for assisting patients to communicate while endotracheally intubated. We also discuss approaches to optimize communication among clinicians, patients, and families about care goals. Challenges for supporting families and planning for transitions between care settings are identified, while the value of interdisciplinary input is emphasized. We review "consultative" and "integrative" models for integrating palliative care and restorative critical care. Finally, we highlight key ethical issues that arise in the care of chronically critically ill patients and their families.


Restoration of liquid effluent from oil palm agroindustry in Malaysia using UV/TiO2 and UV/ZnO photocatalytic systems: A comparative study.
In this study, we have employed a photocatalytic method to restore the liquid effluent from a palm oil mill in Malaysia. Specifically, the performance of both TiO2 and ZnO was compared for the photocatalytic polishing of palm oil mill effluent (POME). The ZnO photocatalyst has irregular shape, bigger in particle size but smaller BET specific surface area (9.71 m2/g) compared to the spherical TiO2 photocatalysts (11.34 m2/g). Both scavenging study and post-reaction FTIR analysis suggest that the degradation of organic pollutant in the TiO2 system has occurred in the bulk solution. In contrast, it is necessary for organic pollutant to adsorb onto the surface of ZnO photocatalyst, before the degradation took place. In addition, the reactivity of both photocatalysts differed in terms of mechanisms, photocatalyst loading and also the density of photocatalysts. From the stability test, TiO2 was found to offer higher stability, as no significant deterioration in activity was observed after three consecutive cycles. On the other hand, ZnO lost around 30% of its activity after the 1st-cycle of photoreaction. The pH studies showed that acidic environment did not improve the photocatalytic degradation of the POME, whilst in the basic environment, the reaction media became cloudy. In addition, longevity study also showed that the TiO2 was a better photocatalyst compared to the ZnO (74.12%), with more than 80.0% organic removal after 22 h of UV irradiation.


Ozonolysis of 2'-deoxycytidine: isolation and identification of the main oxidation products.
The ozone-mediated oxidation of 2'-deoxycytidine (dCyd) was investigated on the basis of final product identification. The oxidation reaction gave rise to five major modified nucleosides which were isolated and characterized on the basis of extensive 1H NMR and mass spectrometry measurements. The comparison with the current knowledge of the hydroxyl radical mediated oxidation reactions of 2'-deoxycytidine in aerated aqueous solution, indicates that the formation of ozone oxidation products may be mostly explained by the opening of the pyrimidine C5-C6 double bond. Thus, the formation of the identified products obtained by ozonolysis of 2'-deoxycytidine is accounted for by the initial generation of an ozonide.


Hyperphagia in dementia: 1. The use of an objective and reliable method for measuring hyperphagia in people with dementia.
Up to one third of dementia sufferers eat an increased quantity of food, compared with their premorbid intake, at some stage during the dementia. A proportion of these eat extraordinarily large quantities if food intake is not restricted. In order to investigate this phenomenon in detail, a reliable and standardized method of quantifying the degree of hyperphagia is required. We report the development of such a method. Twenty-six people with dementia, who were reported by their carers to be hyperphagic, were compared with 14 matched non-hyperphagic controls with dementia and 14 matched normal elderly. Subjects were offered two standardized meals, under specified conditions, ad libitum. One meal consisted of a single food, the other of a mixture of foods. The total energy intake provided a reliable measure of the degree of hyperphagia. The single food meal was more reliable but the mixed meal was a more sensitive measure of the hyperphagia.


Cerebrospinal fluid monoamine metabolites and suicide.
Prospective studies of the serotonergic system and suicide report that low 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and a history of attempted suicide predict suicide risk. Low CSF homovanillic acid (HVA) is reported to be associated with past and future lethality of suicide attempts but not with suicide. The interrelationships between monoamine metabolites, violent method, suicide intent and lethality of suicidal behaviour are complex. We hypothesized that CSF 5-HIAA and HVA levels are related to suicide intent, violence and lethality of suicidal behaviour. Fifteen male suicide attempters admitted to a psychiatric ward at the Karolinska University Hospital and eight healthy male volunteers were submitted to lumbar puncture and CSF 5-HIAA and HVA were assayed. Suicide intent with the Beck Suicide Intent Scale (SIS), lethality and violence of suicidal behaviour were assessed. All patients were followed up for causes of death. Six suicides and one fatal accident were identified with death certificates. Mean CSF 5-HIAA but not CSF HVA differed between suicides and survivors. Violent suicides had higher suicide intent and CSF 5-HIAA than non-violent suicides. In violent suicides, CSF 5-HIAA levels were negatively correlated with SIS. Greater suicide intent may be associated with greater aggressive intent and predicts a violent suicide method.


Effectiveness evaluation of cardiovascular drugs based on CYP2C9 target protein.
This study is to discuss the effectiveness evaluation of cardiovascular drugs based on CYP2C9 target protein. Multilevel fuzzy comprehensive evaluation method was taken to evaluate the individualized medication effectiveness for cardiovascular drug under the function of CYP2P9 target protein. Then, it was established for the index system to affect drug efficacy and index weight was settled. This index system was applied on the study of valsartan drugs to evaluate the drug efficacy rate of sample. Results corresponded with the actual drug treatment, and received better verification. The beneficial exploration was performed for the effectiveness evaluation of individualized administration.


Chameleons everywhere.
We report the case of an HIV-infected man returning from Thailand with secondary syphilis with general symptoms, hepatitis and a pulmonary mass lesion. A cerebrospinal fluid examination showed no signs of neurosyphilis. Two months after successful treatment with benzathine penicillin he presented with a mass lesion in the brain suspected to be a glioma or glioblastoma, which turned out to be a syphilitic gumma. Syphilis remains a great imitator in clinical medicine. Syphilitic brain gummata can develop within a few months.


Management of Deep Neck Space Infections: A Large Tertiary Center Experience.
Deep neck space infections (DNIs) represent serious bacterial infections affecting the deep cervical space and fascial planes of the neck. This study aims to describe our clinical and surgical experience in the management of DNIs, emphasizing the importance of appropriate imaging in the diagnostic setting and the role of the multidisciplinary approach according to the severity of the infection. In this retrospective study, we describe 85 patients affected by DNIs coming to the Otolaryngology department observation from the Emergency Room of San Camillo Forlanini Hospital in Rome from January 2006 to December 2021 and treated both by pharmacological and surgical therapy. 54 patients (64%) were male, and 31 (36%) were female, with a mean age of 50.5 years. The most common cause of DNI was odontogenic, accounting for 70% of all collected cases. In 68 patients (80% of all cases), the surgical approach consisted of an extended unilateral cervicotomy, whereas in 17 patients (20% of all cases), a bilateral cervicotomy was performed. Surgical revision was required in 15 cases (18%). A tracheostomy was necessary in seven cases. The overall survival rate was 96.5%. DNI represents a serious and life-threatening condition, remaining a constant challenge for the head and neck surgeon. Contrast-enhanced computed tomography is critical for therapeutic planning, which requires both a surgical approach and antibiotic therapy. Surgical treatment should be performed as soon as possible. In severe cases, the multidisciplinary approach is advisable.


Elderly patients' satisfaction with the outcome of their health care complaints.
This article profiles the determinants of elderly patients' satisfaction with the outcome of their health care complaints. Type of provider response, severity of complaint, and the individual characteristics of age and cognitive age were found to be significant in effecting satisfaction. Related strategies for managing elderly health care complaints are discussed.


Case Report: Exotropia Surgery in CPEO.
Exotropia in a patient with CPEO was managed with bilateral medial rectus resections. Molecular genetic analysis of DNA from a skeletal muscle biopsy confirmed a deletion of the mitochondrial DNA. The resected muscle tendon was subjected to transmission electron microscopy, revealing muscle fibre variability and ragged red fibres with mitochondrial abnormalities.