Prenatal Alcohol Exposure: Profiling Developmental DNA Methylation Patterns in Central and Peripheral Tissues.
Background: Prenatal alcohol exposure (PAE) can alter the development of neurobiological systems, leading to lasting neuroendocrine, neuroimmune, and neurobehavioral deficits. Although the etiology of this reprogramming remains unknown, emerging evidence suggests DNA methylation as a potential mediator and biomarker for the effects of PAE due to its responsiveness to environmental cues and relative stability over time. Here, we utilized a rat model of PAE to examine the DNA methylation profiles of rat hypothalami and leukocytes at four time points during early development to assess the genome-wide impact of PAE on the epigenome and identify potential biomarkers of PAE. Our model of PAE resulted in blood alcohol levels of ~80-150 mg/dl throughout the equivalent of the first two trimesters of human pregnancy. Hypothalami were analyzed on postnatal days (P) 1, 8, 15, 22 and leukocytes at P22 to compare central and peripheral markers. Genome-wide DNA methylation analysis was performed by methylated DNA immunoprecipitation followed by next-generation sequencing. Results: PAE resulted in lasting changes to DNA methylation profiles across all four ages, with 118 differentially methylated regions (DMRs) displaying persistent alterations across the developmental period at a false-discovery rate (FDR) < 0.05. In addition, 299 DMRs showed the same direction of change in the hypothalamus and leukocytes of P22 pups at an FDR < 0.05, with some genes overlapping with the developmental profile findings. The majority of these DMRs were located in intergenic regions, which contained several computationally-predicted transcription factor binding sites. Differentially methylated genes were generally involved in immune function, epigenetic remodeling, metabolism, and hormonal signaling, as determined by gene ontology analyses. Conclusions: Persistent DNA methylation changes in the hypothalamus may be associated with the long-term physiological and neurobehavioral alterations in observed in PAE. Furthermore, correlations between epigenetic alterations in peripheral tissues and those in the brain will provide a foundation for the development of biomarkers of fetal alcohol spectrum disorder (FASD). Finally, findings from studies of PAE provide important insight into the etiology of neurodevelopmental and mental health disorders, as they share numerous phenotypes and comorbidities.


Clonal maintenance of imprinted expression of SNRPN and IPW in normal lymphocytes: correlation with allele-specific methylation of SNRPN intron 1 but not intron 7.
DNA methylation is a heritable and reversible modification to CpG sites in the mammalian genome. Parental allele-specific methylation is hypothesized to be important in the establishment and maintenance of imprinted gene expression; however, dynamic changes in allele-specific patterns have been observed. The upstream regulatory region of the small nuclear riboprotein N gene (SNRPN) is an important imprinting control region (ICR) for establishing and maintaining the methylation imprint in the locus on 15q11-13 associated with Prader-Willi and Angelman syndromes (PWS). To compare directly the role of allele-specific methylation patterns and the maintenance of imprinted expression in the PWS region, clonal populations of normal T lymphocytes were cultured for 22-25 generations. A novel long-range semi-nested polymerase chain reaction (PCR) strategy was utilized in order to span two different methylation sites, and a polymorphism within SNRPN was used so that allele-specific methylation of both sites could be determined. Reverse transcription/PCR followed by polymorphism analysis was also performed in order to determine parental allele-specific transcription. Exclusive paternal expression at both SNRPN and IPW was maintained in all T cell clones and correlated with maternal methylation of the intron 1 NotI site. In contrast, biallelic methylation was observed in all clones at the previously described paternally methylated HpaII site in intron 7. These results demonstrate that the maintenance of paternal expression of SNRPN and IPW correlates with a strict clonal maintenance of allele-specific methylation at the CpG-dense 5' end of SNRPN. Differential maintenance of methylation sites within imprinted genes may depend on the density and chromatin organization of surrounding CpG sites.


Perceptions Underlying Addictive Technology Use Patterns: Insights for Cognitive-Behavioural Therapy.
Cognitive-Behavioural Therapy (CBT) is considered the 'gold standard' in the treatment of addictive disorders related to excessive technology use. However, the cognitive components of problematic internet use are not yet well-known. The aim of the present study was to explore the cognitive components, that according to problematic users, can lead to potential internet addiction. A total of 854 European adults completed an online survey using a mixed-methods design. Internet problems and attachment styles were assessed, prevalence rates estimated, correlations, chi-squared automatic interaction detection, and content analysis were performed. Self-reported addictions to social networking, internet, and gaming had a prevalence between 1.2% (gaming) to 2.7% (social networking). Self-perception of the addiction problem and preoccupied attachment style were discriminative factors for internet addiction. In an analysis of qualitative responses from self-identified compulsive internet users, a sense of not belonging and feeling of disconnection during life events were perceived as causes for internet addiction. The development depended on a cycle of mixed feelings associated with negative thoughts, compensated by a positive online identity. The severity of this behaviour pattern produced significant impairment in various areas of the participants' functioning, suggesting a possible addiction problem. It is suggested that health professionals administering CBT should target unhealthy preoccupations and monitor mixed feelings and thoughts related to internet use to support coping with cognitive distortions.


Proline is required for male gametophyte development in Arabidopsis.
In crosses between the proline-deficient mutant homozygous for p5cs1 and heterozygous for p5cs2 (p5cs1 p5cs2/P5CS2), used as male, and different Arabidopsis mutants, used as females, the p5cs2 mutant allele was rarely transmitted to the outcrossed progeny, suggesting that the fertility of the male gametophyte carrying mutations in both P5CS1 and P5CS2 is severely compromised. To confirm the fertility defects of pollen from p5cs1 p5cs2/P5CS2 mutants, transmission of mutant alleles through pollen was tested in two ways. First, the number of progeny inheriting a dominant sulfadiazine resistance marker linked to p5cs2 was determined. Second, the number of p5cs2/p5cs2 embryos was determined. A ratio of resistant to susceptible plantlets close to 50%, and the absence of aborted embryos were consistent with the hypothesis that the male gametophyte carrying both p5cs1 and p5cs2 alleles is rarely transmitted to the offspring. In addition, in reciprocal crosses with wild type, about 50% of the p5cs2 mutant alleles were transmitted to the sporophytic generation when p5cs1 p5cs2/P5CS2 was used as a female, while less than 1% of the p5cs2 alleles could be transmitted to the outcrossed progeny when p5cs1 p5cs2/P5CS2 was used as a male. Morphological and functional analysis of mutant pollen revealed a population of small, degenerated, and unviable pollen grains, indicating that the mutant homozygous for p5cs1 and heterozygous for p5cs2 is impaired in pollen development, and suggesting a role for proline in male gametophyte development. Consistent with these findings, we found that pollen from p5cs1 homozygous mutants, display defects similar to, but less pronounced than pollen from p5cs1 p5cs2/P5CS2 mutants. Finally, we show that pollen from p5cs1 p5cs2/P5CS2 plants contains less proline than wild type and that exogenous proline supplied from the beginning of another development can partially complement both morphological and functional pollen defects. Our data show that the development of the male gametophyte carrying mutations in both P5CS1 and P5CS2 is severely compromised, and indicate that proline is required for pollen development and transmission.


Ouabain resistance conferred by expression of the cDNA for a murine Na+, K+-ATPase alpha subunit.
The molecular basis for the marked difference between primate and rodent cells in sensitivity to the cardiac glycoside ouabain has been established by genetic techniques. A complementary DNA encoding the entire alpha 1 subunit of the mouse Na+- and K+-dependent adenosine triphosphatase (ATPase) was inserted into the expression vector pSV2. This engineered DNA molecule confers resistance against 10(-4) M ouabain to monkey CV-1 cells. Deletion of sequences encoding the carboxyl terminus of the alpha 1 subunit abolish the activity of the complementary DNA. The ability to assay the biological activity of this ATPase in a transfection protocol permits the application of molecular genetic techniques to the analysis of structure-function relationships for the enzyme that establishes the internal Na+/K+ environment of most animal cells. The full-length alpha 1 subunit complementary DNA will also be useful as a dominant selectable marker for somatic cell genetic studies utilizing ouabain-sensitive cells.


Protein monoubiquitylation: targets and diverse functions.
Ubiquitin is a 76-amino acid protein whose conjugation to protein targets is a form of post-translational modification. Protein ubiquitylation is characterized by the covalent attachment of the COOH-terminal carboxyl group of ubiquitin to an amino group of the substrate protein. Given that the NH2 -terminal amino group is usually masked, internal lysine residues are most often targeted for ubiquitylation. Polyubiquitylation refers to the formation of a polyubiquitin chain on the substrate as a result of the ubiquitylation of conjugated ubiquitin. The structures of such polyubiquitin chains depend on the specific lysine residues of ubiquitin targeted for ubiquitylation. Most of the polyubiquitin chains other than those linked via lysine-63 and methionine-1 of ubiquitin are recognized by the proteasome and serve as a trigger for substrate degradation. In contrast, polyubiquitin chains linked via lysine-63 and methionine-1 serve as a binding platform for proteins that function in immune signal transduction or DNA repair. With the exception of a few targets such as histones, the functions of protein monoubiquitylation have remained less clear. However, recent proteomics analysis has shown that monoubiquitylation occurs more frequently than polyubiquitylation, and studies are beginning to provide insight into its biologically important functions. Here, we summarize recent findings on protein monoubiquitylation to provide an overview of the targets and molecular functions of this modification.


[Neurodevelopment of extremely low birthweight infants born in Erasmus Hospital between 1992 and 2001].
Survival of extremely low birth weight infants has dramatically improved in the last decade of the twentieth century. The objective of our study was to evaluate the neurological evolution of the surviving infants because frequent motor, sensitive and psychological disturbances are related. Prospective, longitudinal study in a population of newborns, nursed in our neonatal intensive care unit and born between 1992 and 2001 with less than 1.000 g and/or less than 28 weeks of gestational age (GA). Neurological assessment of outcome was made using the neurodevelopmental score (O.M.S. 1988) at 6, 9, 12, 18, 24 and 36 months. Neurological follow-up every year and neuropsychological testing at 3, 5 and 8 years. Only children with at least 2 years of follow-up were included. The children were grouped in 3 categories: M (major neurological handicap), m (minor neurological handicap), N (normal neurological outcome). To evaluate the evolution with time, we compared the results from the first period (1992 to 1996) to the second part of this decade (1997 to 2001). Mortality fell from 38% (27/70) in the first period (1992-1996) to 18% (8/44) in the second one (1997-2001) (p = 0.02) including neonates of less than 25 weeks GA. Neurodevelopmental status improved and severe brain lesions decreased (25% with intraventricular haemorrhage III & IV and cystic periventricular leukomalacia versus 6% in the second period) (p = 0.017). Major handicap fell from 26% (9/34) to 16% (5/31) and normal neurological evolution raised from 15% (5/34) to 48% (15/31) (p = 0.013). With the survival of newborns less than 28 weeks, the severe ocular complications increased: 6% (5/79). In conclusion, mortality and quality of life have significantly improved in the past 10 years in our service. Severe brain lesions have decreased under a better multifactorial management. Nevertheless when the gestational age of the surviving babies diminishes, ocular sequelae increase. We still think that prematurity remains a burden for the child, his family and the society.


Localization of an oligodeoxynucleotide complementing 16S ribosomal RNA residues 520-531 on the small subunit of Escherichia coli ribosomes: electron microscopy of ribosome-cDNA-antibody complexes.
The oligodeoxynucleotide dACCGCGGCTGCT, complementary to Escherichia coli small ribosomal subunit RNA residues 520-531, has been used to probe subunit conformation and to localize the sequence in the subunit. Conditions for binding of the cDNA to 30S subunits were optimized and specificity of the interaction was demonstrated by RNase H cleavage. Three kinds of terminal modification of this cDNA were used to allow its localization by immune electron microscopy. A solid phase support with 5'-dimethoxytrity-N6-delta 2-isopentenyl-adenosine linked to controlled pore glass was synthesized, and used to prepare oligomer with an added 3'-terminal residue of isopentenyl adenosine. cDNA with a 5' primary amine substituent was modified with 1-fluoro-2,4-dinitrobenzene to prepare 5'-dinitrophenyl oligonucleotide, and both modifications together gave doubly-derivatized probes. Immune electron microscopy with antibodies to dinitrophenol, isopentenyl adenosine, or both, was used to place the cDNA on 30S subunits. In each case the probe was placed at a single site at the junction of the head and body of the subunit, near the decoding site and the area in which elongation factor Tu is bound. It is proposed that this segment of ribosomal RNA functions in mRNA binding and orientation.


The RNA Modification Database: 1999 update.
The RNA Modification Database (http://medlib.med.utah.edu/RNAmods/) provides a comprehensive listing of naturally modified nucleosides in RNA. Each file includes: chemical structure; common name and symbol; type(s) of RNA in which found and corresponding phylogenetic distribution; Chemical s registry number and index name; and initial literature citations for structure characterization and chemical synthesis. New features include capability to search database files by name or substructural features, modifications in tmRNA, and links to related data and sites.


Visualization of ischemic insult in caudate putamen with beta-CIT.
Dopamine (DA) has been considered to play an important role in the development of ischemic neuronal injury in the caudate putamen (CPu). The goal of this study was to examine the change in the dopamine transporter (DAT) after ischemic insult in CPu. Male Mongolian gerbils (n = 10) were exposed to 10-min forebrain ischemia. Animals were decapitated 24 hr (n = 5) and 96 hr (n = 5) after ischemia. The change in the amount of DAT binding sites in CPu was evaluated by in vitro autoradiography with [125I]-beta-CIT (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester). In addition, the expression of DAT mRNA in CPu and the substantia nigra pars compacta (SNC) was examined. Iodine-125-beta-CIT specific binding was significantly increased in dorsolateral CPu with ischemic damage both 24 hr and 96 hr after ischemia, with greater increase at 96 hr. DAT mRNA in SNC was also significantly increased 96 hr after ischemia, which corresponded with the increase of [125I] beta-CIT binding. However, DAT mRNA in SNC was decreased 24 hr after ischemia. In the ischemic lesion in CPu, no expression of DAT mRNA could be detected both 24 hr and 96 hr after ischemia. The change in DAT after ischemic insult is clarified with [125I] beta-CIT. This increase of [125I] beta-CIT binding does not come from de novo expression of DAT in glial cells in the damaged area in CPu. This increase of beta-CIT binding reflects increase of DAT synthesis in DA neurons in SNC (96 hr) or other factors such as the impairment of the degradation of DAT in the damaged area in CPu.


Interferon lambda genetic polymorphisms and viral infection: the tip of the iceberg?
Pathogen-host interaction studies have demonstrated the importance of host factors in the pathogenesis of infectious disease. An emerging theme is that polymorphisms in the genes encoding these factors can influence the host response to infection and the course of disease. Genetic variation affecting interferon lambda (IFN-λ) expression is now known to influence the outcome of both hepatitis C virus and herpes simplex virus type 1 infection in humans. IFN-λ is expressed at higher levels in organs with high epithelial cell content such as the respiratory and gastrointestinal tracts. Interestingly, data from animal models show that IFN-λ contributes to host control of viruses infecting these sites, including influenza A virus, severe acute respiratory syndrome coronavirus, and rotavirus. Furthermore, defective IFN-λ production by humans with asthma impairs the control of rhinovirus infection. We hypothesize that genetic variation of IFN-λ could potentially influence the course of disease during infection with many viruses that infect epithelial cells.


Successful use of venovenous extracorporeal membrane oxygenation for complicated H1N1 pneumonia refractory to mechanical ventilation.
In April 2009, novel H1N1 influenza A pneumonia was initially identified in young adults by the Mexican Health Ministry. Previously healthy patients progressing to multisystem organ failure were common. Worldwide, hospitals reported surges in intensive care admissions during the initial phase of the pandemic. In patients with H1N1 pneumonia refractory to mechanical ventilation, centers were initially reporting low survival rates despite the use of extracorporeal membrane oxygenation (ECMO). The initial poor outcomes and protracted ECMO treatment epochs resulted in centers limiting or withholding the use of ECMO in this population. With respect to children with H1N1 infection there was uncertainty concerning optimal incorporation of ECMO as a therapeutic option. In children with rapidly progressive pneumonia and hypoxia refractory to mechanical ventilation, venovenous (VV) ECMO has been successfully used with survival ranging from 40-60% depending on the etiology. We report the successful use of VV ECMO in two children with confirmed novel H1N1 complicated by bacterial pneumonia or morbid obesity. Our Institutional Review Board waived the need for consent. Prompt initiation of VV ECMO resulted in rapid clinical improvement, radiographic resolution of diffuse consolidation, and return of full neurocognitive function. For children with rapidly progressive respiratory distress on conventional ventilation, VV ECMO can be used to improve outcomes when initiated early in the disease process even in children with a significant co-morbidity.


The role of the membrane-bound hydrogenase in the energy-conserving oxidation of molecular hydrogen by Escherichia coli.
H2-dependent reduction of fumarate and nitrate by spheroplasts from Escherichia coli is coupled to the translocation of protons across the cytoplasmic membrane. The leads to H+/2e- stoicheiometry (g-ions of H+ translocated divided by mol of H2 added) is approx. 2 with fumarate and approx. 4 with nitrate as electron acceptor. This proton translocation is dependent on H2 and a terminal electron acceptor and is not observed in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the respiratory inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide. H2-dependent reduction of menadione and ubiquinone-1 is coupled to a protonophore-sensitive, but 2-n-heptyl-4-hydroxy-quinoline N-oxide-insensitive, proton translocation with leads to H+/2e- stoicheiometry of approx. 2. H2-dependent reduction of Benzyl Viologen (BV++) to its radical (BV+) liberates protons at the periplasmic aspect of the cytoplasmic membrane according to the reaction: H2 + 2BV++ leads to 2H+ + 2BV+. It is concluded that the effective proton translocation observed in the H2-oxidizing segment of the anaerobic respiratory chain of Escherichia coli arises as a direct and inevitable consequence of transmembranous electron transfer between protolytic reactions that are spatially separated by a membrane of low proton-permeability.


Accelerated exon evolution within primate segmental duplications.
The identification of signatures of natural selection has long been used as an approach to understanding the unique features of any given species. Genes within segmental duplications are overlooked in most studies of selection due to the limitations of draft nonhuman genome assemblies and to the methodological reliance on accurate gene trees, which are difficult to obtain for duplicated genes. In this work, we detected exons with an accumulation of high-quality nucleotide differences between the human assembly and shotgun sequencing reads from single human and macaque individuals. Comparing the observed rates of nucleotide differences between coding exons and their flanking intronic sequences with a likelihood-ratio test, we identified 74 exons with evidence for rapid coding sequence evolution during the evolution of humans and Old World monkeys. Fifty-five percent of rapidly evolving exons were either partially or totally duplicated, which is a significant enrichment of the 6% rate observed across all human coding exons. Our results provide a more comprehensive view of the action of selection upon segmental duplications, which are the most complex regions of our genomes. In light of these findings, we suggest that segmental duplications could be subjected to rapid evolution more frequently than previously thought.


Chronic Environmental and Occupational Lead Exposure and Kidney Function among African Americans: Dallas Lead Project II.
Background: We examined the effects of lead on kidney function in occupationally and environmentally exposed adults from a Dallas lead smelter community that was the site of an Environmental Protection Agency (EPA) Superfund clean-up. All subjects were African Americans-a racial group that bears a disproportionate burden of kidney disease. Methods: A two-phase health screening was conducted. Phase II included a physical examination and laboratory tests. Study subjects were African Americans residents, aged ≥19 years to ≤89 years. Of 778 subjects, 726 were environmentally exposed and 52 were both occupationally and environmentally exposed. The effects of lead exposure on estimated glomerular filtration rate (eGFR) were examined in three groups: male and female smelter-community residents, as well as males with both occupational and environmental exposure. Multiple linear regression was used to analyze the dependence of eGFR on log (blood lead level), duration of residence in the community, type 2 diabetes, and hypertension. Results: There was a statistically significant negative effect on kidney function for all three groups. Comparison of female and male residents showed a slightly larger negative effect of blood lead level on eGFR in females versus males, with the largest effect seen in male smelter-working residents. For each unit increase (log10 10µg/dL = 1) in blood lead level, age-adjusted eGFR was reduced 21.2 mL/min/1.73 m² in male residents, 25.3 mL/min/1.73 m² in female residents and 59.2 mL/min/1.73 m² in male smelter-working residents. Conclusions: Chronic lead exposure is associated with worsening kidney function in both African American male and female residents, as well as male workers in Dallas smelter communities. This effect is slightly, but not statistically significantly, worse in female residents than male residents, and significantly worse in males that both worked and resided in the smelter community.


Paraneoplastic sensorimotor neuropathy associated with regression of small cell lung carcinoma.
An elderly female smoker presented with nausea and anorexia. Imaging and histopathology were consistent with a diagnosis of small cell lung cancer (SCLC). She subsequently developed a progressive sensorimotor neuropathy with high titres of anti-Hu antibodies. Development of the neuropathy was associated with marked regression in the lung neoplasm. Repeat investigation with radioimaging and bronchoscopy showed no evidence of neoplasia. Paraneoplastic sensorimotor neuropathies are commonly associated with SCLC particularly in the presence of anti-Hu antibodies. Regression of SCLC with anti-Hu antibodies has only been reported twice previously. The authors believe this case supports the theory that anti-Hu antibodies confer anti-tumour activity causing tumour regression.


Using control charts to analyze serial patient-related data.
The authors collected data from the record of a patient who had recently undergone coronary bypass surgery and used these data to construct control charts. The control charts helped them to interpret the variation in several clinical parameters and to evaluate the clinical responses to this variation.


Modernising medical regulation: where are we now?
This paper aims to outline and comment on the changes to medical regulation in the UK that provide the background to a special issue of the Journal of Health Organization and Management on regulating doctors. This paper takes the form of a review. Although the UK medical profession enjoyed a remarkably stable regulatory structure for most of the first 150 years of its existence, it has undergone a striking transformation in the last decade. Its regulatory form has mutated from one of state-sanctioned collegial self-regulation to one of state-directed bureaucratic regulation. The erosion of medical self-regulation can be attributed to: the pressures of market liberalisation and new public management reforms; changing ideologies and public attitudes towards expertise and risk; and high profile public failures involving doctors. The "new" UK medical regulation converts the General Medical Council into a modern regulator charged with implementing policy, and alters the mechanisms for controlling and directing the conduct and performance of doctors. It establishes a new set of relationships between the medical profession and the state (including its agencies), the public, and patients. This paper adds to the literature by identifying the main features of the reforms affecting the medical profession and offering an analysis of why they have taken place.


High Frame-Rate, High Resolution Ultrasound Imaging With Multi-Line Transmission and Filtered-Delay Multiply And Sum Beamforming.
Multi-Line Transmission (MLT) was recently demonstrated as a valuable tool to increase the frame rate of ultrasound images. In this approach, the multiple beams that are simultaneously transmitted may determine cross-talk artifacts that are typically reduced, although not eliminated, by the use of Tukey apodization on both transmission and reception apertures, which unfortunately worsens the image lateral resolution. In this paper we investigate the combination, and related performance, of Filtered-Delay Multiply And Sum (F-DMAS) beamforming with MLT for high frame-rate ultrasound imaging. F-DMAS is a non-linear beamformer based on the computation of the receive aperture spatial autocorrelation, which was recently proposed for use in ultrasound B-mode imaging by some of the authors. The main advantages of such beamformer are the improved contrast resolution, obtained by lowering the beam side lobes and narrowing the main lobe, and the increased noise rejection. This study shows that in MLT images, compared to standard Delay And Sum (DAS) beamforming including Tukey apodization, F-DMAS beamforming yields better suppression of cross-talk and improved lateral resolution. The method's effectiveness is demonstrated by simulations and phantom experiments. Preliminary in vivo cardiac images also show that the frame rate can be improved up to 8-fold by combining F-DMAS and MLT without affecting the image quality.


Healthy buildings: impact on nurses and nursing practice.
Mounting evidence indicates that buildings can be a significant cause of human illness and environmental degradation. According to the United States (US) Environmental Protection Agency, indoor air pollution is one of the top five environmental risks to public health in the US. This may be related, to a large extent, to the fact that US citizens spend as much as 95% of their time indoors. Health care leaders, designers, and architects, recognizing the connection between health and the buildings in which much time is spent, are engaging in sustainable design and construction for healthy, 'green' buildings. The purpose of this article is to assist nurses in understanding the impact that unhealthy buildings can have on nurses and nursing practice and to provide tools and resources to assist nurses in transforming the health care industry with the goal of creating healing environments and reducing the negative environmental impact of the health care industry. First definitions, current initiatives, and motivations related to sustainable designs will be presented. Next sustainable health care design strategies, such as site planning, clean transportation, water conservation, healthy materials selection, indoor environmental quality, and also the benefits of sustainable design will be discussed. The article will conclude by sharing a variety of resources nurses can use to create healing environments in health care settings.


Annual Report of the Australian Gonococcal Surveillance Programme, 2009.
The Australian Gonococcal Surveillance Programme (AGSP) monitors antibiotic susceptibility testing of Neisseria gonorrhoeae isolated in all states and territories. In 2009 the in vitro susceptibility of 3,220 isolates of gonococci from public and private sector sources was determined by standardised methods. Varying antibiotic susceptibility patterns were again seen across jurisdictions and regions. Resistance to the penicillins nationally was 36% and, with the exception of the Northern Territory, ranged between 19% in Queensland and 52% in Victoria. Quinolone resistance, most at high minimal inhibitory concentration (MIC) levels, was 43% nationally (excepting the Northern Territory), and ranging from 30% in Queensland to 60% in Victoria. Decreased susceptibility to ceftriaxone (MIC 0.06 mg/L or more), was found nationally in 2% of isolates. Nationally, all isolates remained sensitive to spectinomycin. Azithromycin resistance surveillance was performed in New South Wales, Queensland, Western Australia, the Northern Territory and South Australia, and was found to be present in low numbers of gonococci with MIC values up to 16 mg/L. In larger urban centres the ratio of male to female cases was high, and rectal and pharyngeal isolates were common in men. In other centres and in rural Australia the male to female ratio of cases was lower, and most isolates were from the genital tract.


A comparison, for older people with diabetes, of health and health care utilisation in two different health systems on the island of Ireland.
There are social and economic differences between Northern Ireland (NI) and the Republic of Ireland (ROI). There are also differences in the health care systems in the two jurisdictions. The aims of this study are to compare health (prevalence of diabetes and related complications) and health care utilisation (general practitioner, outpatient or accident and emergency utilisation) among older people with diabetes in the NI and ROI. Large scale comparable surveys of people over 50 years of age in Northern Ireland (NICOLA, wave 1) and the Republic of Ireland (TILDA, wave 1) are used to compare people with diabetes (type I and type II) in the two jurisdictions. The combined data set comprises 1536 people with diabetes. A coarsened exact matching approach is used to compare health care utilisation among people with diabetes in NI and ROI with equivalent demographic, lifestyle and illness characteristics (age, gender, education, smoking status and self-related health, number of other chronic diseases and number of diabetic complications). The overall prevalence of diabetes in the 50 to 84 years old age group is 3.4 percentage points higher in NI (11.1% in NI, 7.7% ROI, p-value < 0.01). The diabetic population in NI appear sicker - with more diabetic complications and more chronic illnesses. Comparing people with diabetes in the two jurisdictions with similar levels of illness we find that there are no statistically significant differences in GP, outpatient or A&E utilisation. Despite the proximity of NI and ROI there are substantial differences in the prevalence of diabetes and its related complications. Despite differences in the health services in the two jurisdictions the differences in health care utilisation for an equivalent cohort are small.


A phase II study of a dose-density regimen with fluorouracil, epirubicin, and cyclophosphamide on days 1 and 4 every 14 days with filgrastim support followed by weekly paclitaxel in women with primary breast cancer.
Recent evidence shows that use of anthracycline and taxane adjuvant chemotherapy and dose-dense regimens, consisting of more frequent administration of the drugs, have improved outcomes for breast cancer patients. In this study, we evaluated administration of an epirubicin-based regimen with paclitaxel in a sequential, dose-dense schedule as adjuvant treatment for patients with high-risk primary breast cancer. In a phase II Simon two-stage design study, we evaluated the feasibility of a modified fluorouracil, epirubicin, and cyclophosphamide (FEC) regimen at high dose intensity (fluorouracil 500 mg/m(2) i.v. on days 1 and 4, epirubicin 60 mg/m(2) i.v. on days 1 and 4, and cyclophosphamide 500 mg/m(2) i.v. on days 1 and 4; all drugs were administered every 14 days for 3 cycles) with granulocyte colony-stimulating factor support followed by dose-intense weekly paclitaxel 100 mg/m(2) for 8 cycles. In 11 patients with breast cancer following quadrantectomy (n = 8) or modified radical mastectomy (n = 3), any grade 3 (G3) or higher nonhematologic toxicity (excluding alopecia, nausea or vomiting, and bone pain, which might be a consequence of the administration of filgrastim) and adherence to the scheduled dose-dense treatment (deliverability) were monitored with the purpose of enrolling an additional 27 patients in the case of a satisfying toxicity profile and deliverability of the planned treatment (at least 7 patients completing the treatment). Five of 11 patients experienced G3 or higher nonhematologic toxicity during the FEC regimen. We did not observe G3 or higher nonhematologic toxicity related to paclitaxel treatment. In particular, three patients experienced G3 fatigue, one patient had G3 oral mucositis, three patients had G3 hypokalemia, one patient had G3 syncope, one patient had G3 transaminitis (alanine aminotransferase), one patient experienced G4 pulmonary thromboembolism, and 1 patient had a G3 breast infection. Four of 11 patients received the regimen with a 25% dose reduction of day 1 and 4 administrations of FEC. Seven of 11 patients required FEC delay ≥7 days in at least 1 cycle, regardless of dose intensity. Two patients failed to complete the FEC regimen. Two of the remaining 9 patients were treated with paclitaxel delay ≥7 days in at least one cycle. After a median follow-up of 28 months, 9 patients were continuously disease free. The tolerability rate of a dose-density regimen with FEC followed by weekly paclitaxel was considered not promising for completing the accrual of this study.


Posttreatment complications of early-stage prostate cancer patients: brachytherapy versus three-dimensional conformal radiation therapy.
The purpose of this study was to compare treatment complications for early-stage prostate cancer managed by either brachytherapy or three-dimensional conformal radiotherapy (3D-CRT). [corrected] Records were reviewed for 86 men treated with transperineal interstitial permanent prostate brachytherapy and for 76 men treated with dose-escalated (75.6-Gy) six-field 3DCRT between 1998 and 2000. Median ages were 65 and 66 years, respectively; median Gleason scores were 6 and 7; baseline prostate-specific antigen levels were 6.1 and 9.0 ng/mL; and the follow-up period was 42 months. In the urinary domain, patients who underwent brachytherapy recorded an International Prostate Symptom Score prospectively at baseline, as well as 3 months and every 6 months following, whereas patients who underwent 3D-CRT were assigned a Radiation Therapy Oncology Group (RTOG) late toxicity score at similar time intervals. In the bowel domain, RTOG late toxicity score was used for both groups, and physician-dictated notes were used to assess sexual function. All patients who underwent brachytherapy were prescribed tamsulosin (Flomax) to manage urinary symptoms for a minimum of 3 months after treatment. With respect to urinary symptoms, a direct comparison cannot be made between the International Prostate Symptom Score and the RTOG late toxicity score. Nonetheless, it was evident that patients who underwent brachytherapy had more severe urinary sequelae in the months after implantation. Tamsulosin was still being used by 78% of patients at 6 months, decreasing to 55% at 1 year and 27% at 2 years. Intermittent self-catheterization was required at 6 months after treatment by 5% of patients who underwent brachytherapy, and a transurethral resection of the prostate was performed in one of these patients at 12 months. In patients who underwent 3D-CRT, 14% used tamsulosin at some point in the follow-up period and none required catheterization or transurethral resection of the prostate. In the bowel domain, 20% of patients who underwent brachytherapy experienced grade 1 gastrointestinal toxicity, most within the first 12 months of follow-up, compared with 30% grade 1 or 2 gastrointestinal scores in the 3D-CRT group (peaking in the second year after treatment). In the sexual domain, 9% of patients who underwent brachytherapy who were previously potent reported a loss of potency by 18 months, compared with 53% of patients who underwent 3D-CRT. Without the help of sildenafil (Viagra), these figures rose to 24% and 58%. 3D-CRT is associated with fewer urinary symptoms, whereas brachytherapy has a more favorable toxicity profile for bowel and sexual function. In the absence of a randomized clinical trial, such a comparison can be helpful both in counseling patients as to what to expect from either treatment and in facilitating their treatment decision process.


A repeated cross-sectional study of the association of community health worker intervention with the maternal continuum of care in rural Liberian communities.
The maternal continuum of care (CoC) (antenatal care, facility-based delivery, postnatal care) is critical to maternal and neonatal health and reducing mortality, but completion in rural areas of low- and middle-income countries is often limited. We used repeated cross-sectional household surveys from a rural Liberian county to explore changes in rates of completion of all steps and no steps in the maternal CoC after implementation of the National Community Health Assistant Program (NCHAP), a community health worker (CHW) intervention designed to increase care uptake for families over five kilometers from a facility. We analyzed repeated cross-sectional household surveys of women aged 18-49 served by NCHAP in Rivercess County, Liberia. We measured survey-weighted, before-to-after implementation difference in completion of all steps and no steps in the maternal CoC. We used multivariable regression to explore covariates associated with completion rates before and after NCHAP implementation. Data from surveys conducted at three timepoints (2015, n = 354; 2018, n = 312; 2021, n = 302) were analyzed. A significant increase in completing the full maternal CoC (2015:23.6%, 2018:53.4%, change:29.7% points (pp), 95% confidence interval (CI) [21.0,38.4]) and a decrease in completing no steps in the CoC (2015:17.6%, 2018:4.0%, change: -12.4pp [-17.6, -7.2]) after implementation of NCHAP were observed from 2015 to 2018, with rates maintained from 2018 to 2021. Living farther from a facility was consistently associated with less care across the continuum. Following implementation, living in a motorbike accessible community was associated with completing the CoC while living in a mining community was negatively associated with omitting the CoC. Household wealth was associated with differences in rates pre-NCHAP but not post-NCHAP. Following NCHAP implementation, completion rate of the full maternal CoC in Rivercess County more than doubled while the rate of completing no steps in the continuum fell below 5%. These rates were sustained over time including during COVID-19 with reduced differences across wealth groups, although far distances remained a risk for less care. CHW programs providing active outreach to remote communities can be important tools for improving uptake of interventions and reducing risk of no formal care during and after pregnancy.


A systematic review on the impact of point-of-sale tobacco promotion on smoking.
The tobacco retail environment is a crucial marketing medium for the industry. A 2009 review found evidence of a positive association between exposure to point-of-sale (POS) tobacco promotion and increased smoking and smoking susceptibility, though limitations in the evidence base were identified. We reviewed and critically appraised recent evidence documenting the influence of POS tobacco promotion, and POS tobacco display bans, on smoking-related behavior and cognitions. We reviewed original quantitative and qualitative research that examined the relationship between POS tobacco promotion and smoking prevalence, individual-level smoking and quitting and tobacco purchasing behavior, smoking susceptibility, and smoking-related cognitions. Twenty peer-reviewed studies (18 quantitative and 2 qualitative) met the inclusion criteria; each study reported findings consistent with a positive association between exposure to POS tobacco promotion and smoking or smoking susceptibility. Several studies met key criteria for causality: 4 indicated a dose-response association, 2 prospective studies were identified, and evidence from intervention studies supported the reversibility of the association. Findings were consistent across different study designs, settings, and measures. The existing evidence supports a positive association between exposure to POS tobacco promotion and smoking. This review provides evidence to support the continuation of POS tobacco display bans in those jurisdictions where such legislation has been introduced and strengthens the evidence encouraging similar policies in jurisdictions without a POS display ban.


[Quantitative characteristics of the survival phenomenon in experimental plague].
The method for the quantitative evaluation of the effect of the survival phenomenon is proposed, which makes it possible to carry out the rapid single-stage determination of the immunogenicity of Pasteurella pestis avirulent strains. The low specificity of the survival phenomenon in plague has been shown. The accumulation of immunogenic avirulent cells in the population of virulent P. pestis has been found to decrease their pathogenic action to a greater extent than the accumulation of nonimmunogenic avirulent cells.


Modified Van Nes rotationplasty for osteosarcoma of the proximal tibia in children.
Above-knee amputation has been the traditional treatment for osteosarcoma of the proximal tibia. Recent advances in chemotherapy have encouraged the development of limb-salvage techniques. Van Nes rotationplasty for malignant lesions of the distal femur has increased in popularity as a reconstructive technique, but no similar procedure has been described for lesions of the proximal tibia. We have developed a modified rotationplasty for this lesion and have performed it in four children. The surgical technique, postoperative management and results of the procedure are described. Two patients had delayed wound healing. No other complications have developed and our patients were disease-free at follow-up, while the appearance of the leg was well accepted by the patients and their parents. This procedure is a useful addition to the armamentarium of the tumour surgeon for the treatment of malignant lesions of the proximal tibia.


Chemical deglycosylation of ovine pituitary lutropin. A study of the reaction conditions and effects on biochemical, biophysical and biological properties of the hormone.
The oligomeric glycoprotein hormone, ovine lutropin was treated with anhydrous HF at 0 degrees C for 30, 60 and 180 min and at 23 degrees C for 60 and 180 min. The products, designated deglycosylated lutropin 1 (DGLH-1) to deglycosylated lutropin 5 (DGLH-5) respectively, were characterized by gel filtration, concanavalin A-Sepharose binding, disc electrophoresis, amino acid analysis, carbohydrate composition and spectral properties. The preparations were also evaluated for receptor binding activity and immunological activity and bioassayed in vitro in collagenase-dispersed rat interstitial cells. In DGLH-1, fucose and galactosamine were removed completely, and there was a 94% decrease in hexoses and 39% decrease in N-acetylglucosamine. Reaction with HF at 0 degrees C for 1 or 3h led to removal of all hexoses and additional loss of hexosamines. Reactions at 23 degrees C for either 1 or 3h were not of additional value in deglycosylation and none of the reaction conditions yielded the apohormone. All the five deglycosylated hormone preparations were not retained on immobilized-concanavalin A columns and on Sephadex G-100 they were eluted with an increased V(e)/V(0) ratio consistent with the loss of carbohydrate residues. Loss of all but the last of the N-acetylglucosamine residues decreased the abnormality of lutropin on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, but did not eliminate it. Receptor binding activities of DGLH-1 and DGLH-2 were not different from that of the native hormone, but that of DGLH-3 was slightly decreased and the products obtained at 23 degrees C (DGLH-4 and DGLH-5) had lower activity. Immunoreactivities followed a similar pattern. None of the derivatives had activity in the bioassay in vitro. All of the five derivatives inhibited the action of the native hormone in the bioassay in vitro. Their hormonal antagonistic activity was consistent with the receptor binding activity, with DGLH-5 being the least potent in this respect. The DGLH-4 and DGLH-5 preparations had undergone conformational changes as revealed by 8-anilinonaphthalene-1-sulphonate fluorescence, but this did not result in loss of quaternary structure.


Elevated GFAP Protein in Anterior Cingulate Cortical White Matter in Males With Autism Spectrum Disorder.
Based on evidence of abnormalities in axon thickness and neuronal disorganization, autism spectrum disorder (ASD) is commonly considered to be a condition resulting from neuronal dysfunction. Yet, recent findings suggest that non-neuronal cell types also contribute to ASD pathology. To investigate the role of glial cells in ASD, a combination of protein and gene expression analyses were used to determine levels of two glial markers, glial fibrillary acidic protein (GFAP) and myelin oligodendrocyte glycoprotein (MOG), in the postmortem brain tissue from control and ASD donors. Levels of GFAP immunoreactivity (ir) were significantly elevated (P = 0.008) in anterior cingulate cortex (Brodmann area 24; BA24) white matter of ASD donors compared to control donors. In contrast, GFAP-ir levels were similar in BA24 gray matter from ASD and control donors. MOG-ir was also similar in both BA24 white and gray matter from ASD and control donors. In anterior prefrontal cortex (BA10), there were no significant differences in GFAP-ir or MOG-ir in either white or gray matter comparing ASD to control donors. Levels of expression of the genes GFAP and MOG also showed no differences between control and ASD donors in BA24 and BA10 white and gray matter. Collectively, these data imply that ASD is associated with an activation of white matter astrocytes in the anterior cingulate cortex as a result of a yet undefined cellular insult. Research is needed to investigate the molecular pathways that underlie this astrocyte reaction and such research may yield important clues regarding the etiology of ASD.


Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease.
To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. ΔT1 was determined for the three main vascular territories and compared with [15O]H2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). ΔT1 showed a significant but poor correlation with stress MBF (R2 = 0.04, P = 0.03) and MFR (R2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. ≤2.30 mL/min/g) demonstrated attenuated ΔT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, ΔT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of ΔT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57-0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53-0.71, P = 0.07) for diagnosing impaired MFR. CMR stress T1 mapping has poor agreement with [15O]H2O PET measurements of absolute myocardial perfusion. Stress T1 and ΔT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.


Children's understanding and production of verbal irony in family conversations.
This study examined how children use and understand various forms of irony (sarcasm, hyperbole, understatement, and rhetorical questions) in the context of naturalistic positive and negative family conversations in the home. Instances of ironic language in conversations between mothers, fathers, and their two children (M(ages) = 6.33and4.39years) were recorded during six 90-min observations for each of 39 families. Children's responses to others' ironic utterances were coded for their understanding of meaning and conversational function. Mothers were especially likely to ask rhetorical questions and to use ironic language in conflictual contexts. In contrast, fathers used hyperbole and understatement as frequently as rhetorical questions, and employed ironic language in both positive and conflictual contexts. Children also showed evidence of a nascent ability to use ironic language, especially hyperbole and rhetorical questions. Family members used rhetorical questions and understatement proportionately more often in a negative interaction context. Finally, older siblings understood irony better than younger siblings, and both children's responses revealed some understanding of ironic language, particularly sarcasm and rhetorical questions. Overall, the results suggest that family conversations in the home may be one important context for the development of children's use and understanding of ironic language.


Boron stimulates embryonic trout growth.
Boron is present in our soil, water and air. Cyanobacteria require it for nitrogen fixation, and vascular plants require it for the formation of cell walls and membranes. I report here how boron affects the growth of embryonic rainbow trout (Oncorhynchus mykiss). Fertilized ovum from the Mt. Whitney rainbow trout strain were incubated at (12.5 degreesC) in Type 1 ASTM ultrapure grade water supplemented with boric acid (99.5% purity) during the 1995 and 1997 spawning seasons. Boron concentrations of the incubation solutions were determined by direct measurement using the curcumin procedure or inductively coupled plasma-mass spectrometry. In the 1995 study boron ranged from 1 to 936 micromol/L. Ca, Na and Mg salts were included in the incubation solutions to approximate concentrations in natural water. In the 1997 study fertilized eggs were incubated in ultrapure water supplemented with boric acid alone over a range from 2.2 to 90.6 micromol/L. The 1995 study used 144 embryos per B concentration and the 1997 study used 96 embryos per B concentration. Growth and teratogenicity were evaluated at the eye, hatch and 2-wk posthatch developmental stages. Boron stimulated growth in a dose-dependent manner in both studies (P < 0.001), and exposure was associated with an increase in B body concentration (P < 0.05). No teratogenic or microbicidal effects were apparent. These results are consistent with those expected of an element essential for vertebrate development. J. Nutr. 2488-2493, 128: 1998


Topographic mapping of left ventricular regional contractile injury in ischemic mitral regurgitation.
Restrictive leaflet tethering resulting from regional left ventricular (LV) contractile injury causes ischemic mitral regurgitation (MR). We hypothesized that 3-dimensional LV topographic mapping by MRI-based multiparametric strain analysis could characterize the regional contractile injury patterns that differentiate ischemic coronary artery disease patients who have ischemic MR from those who do not. Magnetic resonance imaging-based multiparametric strain data were calculated for 15,300 LV grid points in 100 normal volunteers. Strain parameters from ischemic MR (n = 10) and ischemic no-MR (n = 36) patients were then normalized to this normal human strain database with z score quantification of standard deviation from the normal mean. Mean multiparametric strain z scores were calculated for 18 LV subregions (basilar/mid/apical levels; 6 LV regions). Mean strain z scores for papillary muscle-related (basilar/mid levels of anterolateral, posterolateral, and posterior) and nonpapillary muscle-related (all other) subregions were compared between ischemic MR and ischemic no-MR groups. Across all patients, contractile injury was greater in the papillary muscle-related regions compared with the nonpapillary regions (P = .007). In the papillary regions, contractile injury was greater in the ischemic MR group compared with the no-MR group (z scores, 1.91 ± 1.13 vs 1.20 ± 1.01, respectively; P < .001). Strain values in the nonpapillary muscle-related subregions were not different between the 2 groups (1.31 ± 1.04 vs 1.20 ± 1.03; P = .301). Multiparametric strain analysis demonstrated severe normalized contractile injury in the papillary muscle-related LV subregions in patients with ischemic MR. The mean degree of normalized injury approached 2 standard deviations and was significantly worse than the levels seen in ischemic no-MR patients.


The Development of Health for Hearts United: A Longitudinal Church-based Intervention to Reduce Cardiovascular Risk in Mid-life and Older African Americans.
This article describes Health for Hearts United, a longitudinal church-based intervention to reduce cardiovascular disease (CVD) risk in mid-life and older African Americans. Using community-based participatory research (CBPR) approaches and undergirded by both the Socio-ecological Theory and the Transtheoretical Model of Behavior Change, the 18-month intervention was developed in six north Florida churches, randomly assigned as treatment or comparison. The intervention was framed around three conceptual components: awareness building (individual knowledge development); clinical learning (individual and small group educational sessions); and efficacy development (recognition and sustainability). We identified three lessons learned: providing consistency in programming even during participant absences; providing structured activities to assist health ministries in sustainability; and addressing changes at the church level. Recommendations include church-based approaches that reflect multi-level CBPR and the collaborative faith model.


[Challenges and advances in diagnostics, prevention and treatment of hepatorenal syndrome].
Hepatorenal syndrome (HRS) is an exclusion diagnosis in patients with decompensated liver cirrhosis. True hepatic functional insufficiency is sometimes unobvious. Differential diagnostics of HRS encounters difficulty despite new diagnostic criteria. HRS can be prevented by the correct treatment of portal hypertension and hepatic insufficiency under careful monitoring. Effective conservative therapy may significantly change the short-term prognosis and facilitate remission in selected patients. Terlipressin is the agent of choice for HRS therapy aimed at the promotion of intrahospital survival for the subsequent referral of the patient to liver transplantation.


MicroRNA profiling study reveals miR-150 in association with metastasis in nasopharyngeal carcinoma.
MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.


Photorefractive keratectomy in posterior polymorphous dystrophy with vesicular and band subtypes.
To evaluate the safety and efficacy of photorefractive keratectomy (PRK) in patients with posterior polymorphous dystrophy (PPMD) with vesicular and band subtypes. Walter Reed Center for Refractive Surgery, Washington, DC, USA. Case series. The records of patients with PPMD who had PRK between January 2002 and May 2009 were reviewed. Data for analysis included sex, age, ablation depth, residual stromal bed thickness, manifest spherical equivalent, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, central corneal thickness (CCT), endothelial cell density (ECD), intraocular pressure (IOP), and complications. Preoperative and postoperative results were compared using the Wilcoxon signed-rank test, with P < .05 considered significant. Fourteen eyes of 7 men (mean age 29.1 years ± 9.1 [SD]; range 21 to 42 years) with at least a 6-month follow-up were reviewed. At the final follow-up (mean 19.5 months; range 6.3 to 58.3 months), all eyes had a UDVA of 20/15 and all eyes were within ± 0.50 diopter of emmetropia. The CDVA was unchanged from preoperatively in 71.4% of eyes and improved by 1 line in 28.6%. There were no significant complications. The IOP did not change significantly over the follow-up (P = .272). At the final visit, the mean ECD (2795.3 ± 366.0 cells/mm(2)) was unchanged from baseline (2809.1 ± 338.3 cells/mm(2)) (P = .114). Photorefractive keratectomy in PPMD patients with vesicular and band subtypes resulted in excellent visual outcomes and a low incidence of adverse effects. Endothelial cell densities did not change significantly in the early postoperative period. No author has a financial or proprietary interest in any material or method mentioned.


Impaired recognition of scary music following unilateral temporal lobe excision.
Music constitutes an ideal means to create a sense of suspense in films. However, there has been minimal investigation into the underlying cerebral organization for perceiving danger created by music. In comparison, the amygdala's role in recognition of fear in non-musical contexts has been well established. The present study sought to fill this gap in exploring how patients with amygdala resection recognize emotional expression in music. To this aim, we tested 16 patients with left (LTR; n = 8) or right (RTR; n = 8) medial temporal resection (including amygdala) for the relief of medically intractable seizures and 16 matched controls in an emotion recognition task involving instrumental music. The musical selections were purposely created to induce fear, peacefulness, happiness and sadness. Participants were asked to rate to what extent each musical passage expressed these four emotions on 10-point scales. In order to check for the presence of a perceptual problem, the same musical selections were presented to the participants in an error detection task. None of the patients was found to perform below controls in the perceptual task. In contrast, both LTR and RTR patients were found to be impaired in the recognition of scary music. Recognition of happy and sad music was normal. These findings suggest that the anteromedial temporal lobe (including the amygdala) plays a role in the recognition of danger in a musical context.


Respiratory Muscle Strength and Exercise Performance in Cystic Fibrosis-A Cross Sectional Study.
Introduction: Decreased respiratory muscle strength in patients with cystic fibrosis (CF) may cause progressive exercise intolerance during cardiopulmonary exercise testing (CPET), and may contribute to the development of chronic respiratory insufficiency. The aim of this study is to evaluate exercise tolerance during CPET of children and adults with clinically stable CF who exhibit different respiratory muscle strength. Methods: Sixty-nine clinically stable CF subjects aged 8-33 years underwent spirometry, body plethysmography, CPET, and respiratory muscle strength measurement. Respiratory muscle strength was measured using maximal inspiratory pressures (Pimax) and maximal expiratory pressures (Pemax). Participants were stratified into three groups according to Pimax values:below normal (≤80% predicted), normal (81-100% predicted), and above normal (>100% predicted). A similar stratification of participants was made according to Pemax values. The oxygen consumption on peak load (VO2peak) was expressed relative to BM (VO2peak/kg), relative to BM raised by the exponent of 0.67 (VO2peak/kg0.67) and as log-linear adjustment of VO2peak (VO2peak/kg-alo). Results: Participants with low Pemax values had a lower mean maximum load per kilogram/predicted (Wmax; p = 0.001) VO2peak/kg (p = 0.006), VO2peak/kg0.67 (p = 0.038) and VO2peak/kg-alo (p = 0.001). There were no significant differences in exercise tolerance parameters with regard to Pimax values. Stepwise multiple linear regressions confirmed that Pemax (B = 24.88, β = 0.48, p < 0.001) was the most powerful predictor of Wmax. There were no statistically significant differences in age, lung function parameters, exacerbation score, or respiratory muscle strength according to gender. Conclusions: In subjects with clinically stable CF, expiratory muscle strength is associated with a decrease in exercise performance during CPET and can predict exercise intolerance. Increase in expiratory muscle strength by patient specific rehabilitation protocols would result in improvement of exercise tolerance.


Heat transfer mechanisms and thermal dosimetry.
The heat transfer mechanisms that led to the development of the bioheat equation are reviewed. Thermal modeling and analytical judgments which must be made in application of the equation are noted. Temperature profiles that result from solution of the equation with a simple spherical model are considered with particular emphasis on the influence of thermal conductivity and perfusion. Thermal conductivity values of a host of both normal and tumor tissues are discussed. The importance of adequate macroscopic thermal dosimetry to the evaluation of the ultimate promise of hyperthermia is observed. Experience in the quantification of temperature, thermal conductivity, thermal diffusivity, and perfusion from a single, minimally invasive measurement in small volumes of tissue with the thermal diffusion probe is presented.


Graphitic nanocapsules: design, synthesis and bioanalytical applications.
Graphitic nanocapsules are emerging nanomaterials which are gaining popularity along with the development of carbon nanomaterials. Their unique physical and chemical properties, as well as good biocompatibility, make them desirable agents for biomedical and bioanalytical applications. Through rational design, integrating graphitic nanocapsules with other materials provides them with additional properties which make them versatile nanoplatforms for bioanalysis. In this feature article, we present the use and performance of graphitic nanocapsules in a variety of bioanalytical applications. Based on their chemical properties, the specific merits and limitations of magnetic, hollow, and noble metal encapsulated graphitic nanocapsules are discussed. Detection, multi-modal imaging, and therapeutic applications are included. Future directions and potential solutions for further biomedical applications are also suggested.


Memory in narratives and stories: implications for nursing research.
Memory, as a concept, is rarely discussed or described in qualitative research. However, memories are central to the stories people tell about their experiences of health and illness, which are often the focus of nursing enquiry. Memories also have the potential to be sensitive or traumatic. To consider the implications of memory for qualitative research by exploring the following issues: What is memory? What are the implications for using it in research? How can research participants and researchers best be supported in qualitative research when sensitive or traumatic memories are involved? Memory is imperfect, complex and dependent on context. Memories are connected to meaning and are central to identity. Qualitative research should appreciate the complexities of memory. Nurses undertaking qualitative research should be mindful of the potentially sensitive or traumatic nature of memories. Both participants and researchers can be affected and care should be taken during the research. Memory should not be taken for granted. The meanings underpinning memories are central to qualitative enquiry and are to be valued. The strategies described in this paper can support researchers and participants when dealing with traumatic or sensitive memories.


The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males.
Osteocalcin has been proposed to be a novel link between bone and energy metabolism. Previous studies showed its relations to exercise, body fat and glucose metabolism, but their interrelationship remains inconslusive. We evaluated the changes in osteocalcin level following 8-week exercise programme and assessed how they are related to concomitant changes in body fat composition, insulin resistance and various adipocytokines in a single centre, randomized and prospective design. A total of 39 young obese, otherwise healthy males were randomly assigned to control (n = 10) and exercise (n = 29) groups. Subjects in Exercise group were on 8-week supervised exercise training programme of four sessions per week. Body fat compositions were analysed using whole body bone mineral density, various metabolic parameters, osteocalcin and adipocytokines were assessed from fasting blood samples before and after 8-week exercise programme. Body fat reduction following exercise significantly increased serum total (1·51 ± 0·36 vs 1·69 ± 0·39 mmol/l, P = 0·01, baseline vs postexercise) and undercarboxylated osteocalcin level (0·44 ± 0·14 vs 0·64 ± 0·26 mmol/l, P < 0·01), and the increase in osteocalcin was in negative correlations with changes in body weight, BMI and body fat percentage as well as HOMA-IR and leptin (all P < 0·05). The changes in osteocalcin and leptin were not independent predictors of changes in insulin resistance and osteocalcin, respectively. In a physiological axis of bone-fat-energy metabolism, exercise-induced body fat reduction and improved insulin sensitivity were accompanied by an increase in serum osteocalcin and leptin levels, but other factors also seem to be involved in this interrelationship.


Aza-boron-dipyrromethene dyes: TD-DFT benchmarks, spectral analysis and design of original near-IR structures.
The excited-state energies of aza-boron-dipyrromethene (Aza-BODIPY) derivatives are investigated with Time-Dependent Density Functional Theory (TD-DFT), with twin goals. On the one hand, a pragmatic, yet efficient, computational protocol is defined in order to reach rapidly semi-quantitative estimates of the λ(max) of these challenging dyes. It turned out that a PCM-TD-BMK/6-311+G(2d,p)//PCM-PBE0/6-311G(2d,p) approach delivers appropriate lower bounds of the experimental results, despite the inherent limits of the vertical approximation. On the other hand, the method is applied to design new dyes absorbing in the near-IR. The spectral features of ca. 30 new compounds have been simulated in a systematic way, trying to efficiently combine several available synthetic strategies leading to significant bathochromic displacements. A series of dyes absorbing above 850 nm are proposed, illustrating that (relatively) fast theoretical calculations might be a useful pre-screening step preceding synthesis.


The improvement of quality of life in patients treated with bariatric surgery in Korea.
Bariatric surgery is considered an efficient treatment for severe obesity, but postoperative complications and psychosocial problems may impact quality of life (QoL). Although QoL is an important aspect of bariatric surgery, few studies have evaluated the changes in QoL. We examined whether severely obese patients who had undergone bariatric surgery had better QoL compared with severely obese adults who had not undergone bariatric surgery in Korea. Data were obtained from 78 participants in two groups; bariatric surgery group (n = 53) and nonsurgery group (n = 25). EuroQoL-5D (EQ-5D), the impact of weight on quality of life-lite (IWQoL-lite) and the obesity-related psychosocial problem scale (OP-scale) were used to assess the improvement of QoL. A total of 78 patients completed the QoL forms as part of their surgical consultation. In the EQ-5D, the changes of EQ-5D 3 level and EQ-5D visual analogue scale in the surgery group was 0.174 and 24.6 versus 0.017 and 17.8 in the nonsurgery group (P = 0.197 and P = 0.179). The changes of IWQoL-lite and OP-scale were significantly improved after bariatric surgery. In the IWQoL-lite, the mean changes in the surgery group was 33.4 versus 14.3 points in the nonsurgery group (P = 0.000). In the OP-scale, the mean changes in the surgery group patients scored 39.3 versus 9.0 points in the nonsurgery group (P = 0.000). We demonstrated significant improvement of QoL observed after bariatric surgery compared to nonsurgical procedure. The results of this comparative study favor bariatric surgery for the treatment of severe obesity.


Leiomyosarcoma of inferior vein cava presenting as acute Budd-Chiari syndrome.
We report a 49-year-old lady who presented with acute Budd-Chiari syndrome. Spiral CT scan showed inferior vein cava (IVC) tumor and ischemia of the right liver secondary to hepatic vein blockage. These were confirmed by MRI scan and IVC gram, at which time tissue diagnosis was obtained. At surgery, the tumor was seen to originate from the infrahepatic IVC and extended to the level of the diaphragm, blocking the hepatic vein outflow. The tumor was excised completely. Histology confirmed it to be leiomyosarcoma of the IVC. The patient is well, without recurrence of symptoms or tumor, 10 months later.


Horner's syndrome: an unusual presentation of Hodgkin's disease.
Horner's Syndrome (ptosis, anisocoria, and anhydrosis) developed in a 22-year-old woman. A mediastinal mass was noted on chest x-ray. Further evaluation led to a diagnosis of Hodgkin's disease, nodular sclerosis type. Horner's syndrome is an unusual initial manifestation of Hodgkin's disease, and, in this case, it was due to oculosympathetic damage from mediastinal compression. Because the potential for cure is high in Hodgkin's disease, this diagnosis should be considered in patients presenting with Horner's syndrome.


Nutritional needs, resources, and barriers among unhoused adults cared for by a street medicine organization in Chicago, Illinois: a cross-sectional study.
Those experiencing houselessness rely on obtaining food from community organizers and donations. Simultaneously, the houseless face disproportionally high rates of medical conditions that may be affected by diet including diabetes, hypertension, and hyperlipidemia. There is limited literature on the resources and barriers of the houseless community regarding optimal nutrition from an actionable perspective. Further, less data is available on how street medicine organizations may best impact the nutrition of the unhoused they serve. Elucidating this information will inform how organizational efforts may best support the nutrition of the houseless community. In partnership with the medical student-run organization, Chicago Street Medicine, at Northwestern University Feinberg School of Medicine, twenty adults experiencing houselessness in Chicago, Illinois participated in the cross-sectional study. A 10-item survey was verbally administered to characterize the participants' daily food intake, food sources, barriers, resources, and nutritional preferences and needs. All data was directly transcribed into REDCap. Descriptive statistics were generated. Individuals consumed a median of 2 snacks and meals per day (IQR: 1-3). No participant consumed adequate servings of every food group, with only one participant meeting the dietary intake requirements for one food group. Participants most often received their food from donations (n = 15), purchasing themselves (n = 11), food pantries (n = 4), and shelters (n = 3). Eleven of nineteen participants endorsed dental concerns as a major barrier to consuming certain foods. Twelve participants had access to a can opener and twelve could heat their meals on a stove or microwave. Seven had access to kitchen facilities where they may prepare a meal. Approximately half of participants had been counseled by a physician to maintain a particular diet, with most related to reducing sugar intake. Most houseless participants were unable to acquire a balanced diet and often relied on organizational efforts to eat. Organizations should consider the chronic health conditions, dentition needs, and physical resources and barriers to optimal nutrition when obtaining food to distribute to the unhoused.


Effect of oral infection of La Crosse virus on survival and fecundity of native Ochlerotatus triseriatus and invasive Stegomyia albopicta.
Arboviruses can have benign, deleterious, or beneficial effects on the vector. We tested the hypothesis that oral infection with La Crosse virus (LACV) will have little to no effect on mosquito longevity and fecundity, a prediction of low virulence selected in a system with frequent vertical transmission. We tested the effects of infection in native Ochlerotatus triseriatus Say and invasive Stegomyia albopicta Skuse (Diptera: Culicidae). We artificially fed adult female mosquitoes of each species with either LACV-infected or uninfected bovine blood and determined adult longevity and fecundity. For females fed LACV-infected blood, bodies and legs, respectively, were separately homogenized and assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to determine the LACV infection and dissemination rates. Ochlerotatus triseriatus had a higher infection and dissemination rate than St. albopicta. For both species, female size had no effect on infection status. Infection status also had no effect on longevity or fecundity for both species. We suggest that the high frequency of vertical transmission may have selected for strains of the virus with low virulence in two vectors, in spite of their different evolutionary histories with the virus.


[Thymus surgery in a general surgery department].
Evaluation of thymectomy cases between 1990-2003, in a General Surgery Department. Evaluation of the therapeutic efficacy in Miastenia Gravis patients. Retrospective study based on evaluation of data from Serviço de Cirurgia, Neurologia and Consult de Neurology processes, between 1990-2003, of 15 patients submitted to total thymectomy. 15 patients, aged 17 to 72, 11 female and 4 male. Miastenia Gravis was the main indication for surgery, for uncontrollable symptoms or suspicion of thymoma. In patients with myasthenia, surgery was accomplish after compensation of symptoms. There weren't post-surgery complications. Pathology were divided in thymic hyperplasia and thymoma. Miastenia patients have there symptoms diminished or stable with reduction or cessation of medical therapy. Miastenia was the most frequent indication for thymectomy. Surgery was good results, with low morbimortality, as long as the protocols are respected.


A checklist of the basidiomycetous macrofungi and a record of five new species from mt. Oseo in Korea.
Basidiomycetous macrofungi play important roles in maintaining forest ecosystems via carbon cycling and the mobilization of nitrogen and phosphorus. To understand the impact of human activity on macrofungi, an ongoing project at the Korea National Arboretum is focused on surveying the macrofungi in unexploited areas. Mt. Oseo was targeted in this survey because the number of visitors to this destination has been steadily increasing, and management and conservation plans for this destination are urgently required. Through 5 field surveys of Mt. Oseo from April to October 2012, 116 specimens of basidiomycetous macrofungi were collected and classified. The specimens were identified to the species level by analyzing their morphological characteristics and their DNA sequence data. A total of 80 species belonging to 57 genera and 25 families were identified. To the best of our knowledge, this is the first study to identify five of these species-Artomyces microsporus, Hymenopellis raphanipes, Pholiota abietis, Phylloporus brunneiceps, and Sirobasidium magnum-in Korea.


Effects of oxaliplatin on mouse myenteric neurons and colonic motility.
Oxaliplatin, an anti-cancer chemotherapeutic agent used for the treatment of colorectal cancer, commonly causes gastrointestinal side-effects such as constipation, diarrhoea, nausea, and vomiting. Damage to enteric neurons may underlie some of these gastrointestinal side-effects, as the enteric nervous system (ENS) controls functions of the bowel. In this study, neuronal loss and changes to the structure and immunoreactivity of myenteric neuronal nitric oxide synthase (nNOS) neurons were examined in colonic segments from mice following exposure to oxaliplatin ex vivo and following repeated intraperitoneal injections of oxaliplatin over 3 weeks in vivo, using immunohistochemistry and confocal microscopy. Significant morphological alterations and increases in the proportion of NOS-immunoreactive (IR) neurons were associated with both short-term oxaliplatin exposure and long-term oxaliplatin administration, confirming that oxaliplatin causes changes to the myenteric neurons. Long-term oxaliplatin administration induced substantial neuronal loss that was correlated with a reduction in both the frequency and propagation speed of colonic migrating motor complexes (CMMCs) in vitro. Similar changes probably produce some symptoms experienced by patients undergoing oxaliplatin treatment.


Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study.
Polymorbidity induces polypharmacy in older patients may lead to potential drug-drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment. ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment. One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities - irrespective of grade and type - than patients who received standard treatment (p<0.001) and had comparable overall survival (Log rank p=0.21). This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity.


Isolation and expression analysis of genes encoding MET, CMT, and DRM methyltransferases in oil palm (Elaeis guineensis Jacq.) in relation to the 'mantled' somaclonal variation.
In oil palm (Elaeis guineensis Jacq.), approximately 5% of somatic embryo-derived regenerants show homeotic changes during floral development, involving an apparent feminization of male parts in flowers of both sexes, called the 'mantled' phenotype. This variant phenotype is associated with a reduction in the level of global DNA methylation. To explore possible relationships between DNA methylation level and accumulation of DNA-(cytosine-5) methyltransferase (DNMT) transcripts, the full-length coding sequences corresponding to three different DNMT families in oil palm, namely the MET, CMT, and DRM classes, have been isolated and characterized. The corresponding genes were designated as EgMET1, EgCMT1, and EgDRM1, and encode predicted polypeptides of 1543, 925, and 591 amino acid residues, respectively. Expression of oil palm DNMTs was compared between normal and variant calli and inflorescence tissues using quantitative reverse-transcription PCR. A consistent increase in transcript levels of EgMET1 and EgCMT1 was found in variant fast-growing calli relative to nodular-compact calli. Nodular-compact calli give rise to about 5% of abnormal regenerants whereas fast-growing calli generate 95% of 'mantled' palms in their clonal offspring and were previously demonstrated as having markedly hypomethylated DNA. In immature abnormal inflorescences only EgMET1 transcript levels were increased, while no changes in relative abundance of the EgCMT1 or EgDRM1 transcripts were observed. Therefore, the genome-wide hypomethylation previously described in 'mantled' material cannot be explained by a decrease in expression levels of the de novo or maintenance DNMTs, a paradox which has been previously reported in tumour cells, where there is evidence for global hypomethylation of DNA.


Simultaneous optical recording of activity from many neurons during feeding in Navanax.
Optical methods for monitoring changes in membrane potential have been used to measure action potential activity in the buccal ganglion of an opisthobranch mollusc, Navanax inermis, while the animal was feeding. During feeding activity was detected in 10-15% of the approximately 200 neurons present in the ganglion. Control experiments carried out to determine the completeness of the optical recording showed that activity in at least 70% of the neurons could be detected. Thus, in certain invertebrate ganglia, it is possible to make a reasonably complete recording of the neuron activity responsible for generating relatively complex behaviors.


The Six-Step Lower Blepharoplasty: Using Fractionated Fat to Enhance Blending of the Lid-Cheek Junction.
Lower lid blepharoplasty is one of the most complex procedures performed by plastic surgeons and may cause significant long-term sequelae, including inadequate aesthetic outcomes if not performed with a thorough understanding of anatomy and proper technique. The authors' practice is consistently evolving to deliver the highest quality results for their patients. The purpose of this article is to introduce an additional sixth step to the lower lid blepharoplasty procedure involving the targeted injection of fractionated fat to better blend the lid-cheek junction. This added step will enhance overall facial rejuvenation, is reproducible, and will provide patients with exceptional outcomes.


A miR-125b/CSF1-CX3CL1/tumor-associated macrophage recruitment axis controls testicular germ cell tumor growth.
Tumor growth is modulated by crosstalk between cancer cells and the tumor microenvironment. Recent advances have shown that miRNA dysfunction in tumor cells can modulate the tumor microenvironment to indirectly determine their progression. However, this process is poorly understood in testicular germ cell tumors (TGCTs). We reported here that miR-125b was repressed in TGCT samples by epigenetic modifications rather than genetic alternations. Furthermore, miR-125b overexpression significantly alleviated the tumor growth in two NCCIT human embryonic carcinoma xenograft models in vivo, whereas miR-125b did not stimulate autonomous tumor cell growth in vitro. Notably, forced expression of miR-125b in NCCIT embryonic carcinoma cells decreased the abundance of host tumor-associated macrophages (TAMs) within tumor microenvironment. Selective deletion of host macrophages by clodronate abolished the anti-tumoral ability of miR-125b in xenograft models. By RNA profiling, Western blot and luciferase reporter assay, we further observed that miR-125b directly regulated tumor cell-derived chemokine CSF1 and CX3CL1, which are known to control the recruitment of TAMs to tumor sites. Lastly, we found that one set of miRNAs, which are under the regulation of miR-125b, might convergently target CSF1/CX3CL1 in NCCIT cells using miRNA profiling. These findings uncover the anticancer effect of miR-125b via mediating tumor-stroma crosstalk in xenograft models of TGCTs and raise the possibility of targeting miR-125b as miRNA therapeutics.


Surgical treatment of hydatid cyst of the lung: review of 30 cases.
Hydatid cyst disease is still a problem in Turkey, especially in the east Anatolian region, as well as in many other places in the world. A retrospective review was made of the surgical treatment of 30 patients with pulmonary hydatid cysts during the last 3 yrs. Nineteen patients were male and 11 female with an average age of 23.5 yrs (range 4-44 yrs). Cystotomy and capitonnage were performed in 28 of the 30 cases (93.4%). The transdiaphragmatic route or simultaneous laparotomy was preferred when the liver was involved. Albendazole was used in four patients with multiple hydatid cyst due to probable recurrence in the postoperative period. Cough and chest pain were the prominent symptoms in the majority of cases. A single lobe was affected in 22 patients. Unilateral multiple foci were present in four patients and bilateral multiple foci in four. Six patients had concomitant liver cysts. Morbidity was low and no mortality was seen. No recurrences were seen on control chest radiographs during the last 2-yr follow-up. In the treatment of hydatid cyst of the lung, conservative surgical methods such as cystotomy and capitonnage still remain the treatment of choice. Medical treatment could be used for prophylactic purposes and in some instances, but the percutaneous aspiration method should not be performed.


Apoptosis: Historical perspectives.
Apoptosis is one of the most widely studied fields in biology and accounts for over 2% of all life science publications annually. It plays a fundamental role in development, and defects in the regulation of apoptosis are directly implicated in numerous well-known diseases including cancer, neurodegenerative disorders, tissue atrophy and auto-immune diseases. However, the field of apoptosis has humble beginnings and was neglected by biologists for much of its history. This chapter reviews the history of research in apoptosis and highlights key experiments that have contributed significantly to our current understanding of apoptosis. In addition, the topics covered in later chapters are briefly introduced.


A conserved mechanism for JNK-mediated loss of Notch function in advanced prostate cancer.
Dysregulated Notch signaling is a common feature of cancer; however, its effects on tumor initiation and progression are highly variable, with Notch having either oncogenic or tumor-suppressive functions in various cancers. To better understand the mechanisms that regulate Notch function in cancer, we studied Notch signaling in a Drosophila tumor model, prostate cancer-derived cell lines, and tissue samples from patients with advanced prostate cancer. We demonstrated that increased activity of the Src-JNK pathway in tumors inactivated Notch signaling because of JNK pathway-mediated inhibition of the expression of the gene encoding the Notch S2 cleavage protease, Kuzbanian, which is critical for Notch activity. Consequently, inactive Notch accumulated in cells, where it was unable to transcribe genes encoding its target proteins, many of which have tumor-suppressive activities. These findings suggest that Src-JNK activity in tumors predicts Notch activity status and that suppressing Src-JNK signaling could restore Notch function in tumors, offering opportunities for diagnosis and targeted therapies for a subset of patients with advanced prostate cancer.


Comparing the consequences of induced and constitutive plant resistance for herbivore population dynamics.
Although it has been suggested that induced and constitutive plant resistance should have different effects on insect herbivore population dynamics, there is little experimental evidence that plant resistance can influence herbivore populations longer than one season. We used a density-manipulation experiment and model fitting to examine the effects of constitutive and induced resistance on herbivore dynamics over both the short and long term. We used likelihood methods to fit population dynamic models to recruitment data for populations of Mexican bean beetles on soybean varieties with no resistance, constitutive resistance, or induced resistance. We compared model configurations that fit parameters for resistance types separately to models that did not account for resistance type. Models representing the hypothesis that the three resistance types differed in their effects on beetle dynamics received the most support. Induced resistance resulted in lower population growth rates and stronger density dependence than no resistance. Constitutive resistance resulted in lower population growth rates and stronger density dependence than induced resistance. Constitutive resistance had a stronger effect on both short-term beetle recruitment and predicted beetle population dynamics than induced resistance. The results of this study suggest that induced and constitutive resistance can differ in their effects on herbivore populations even in a relatively complex system.


Environmental and economic trade-offs in a watershed when using corn stover for bioenergy.
There is an abundant supply of corn stover in the United States that remains after grain is harvested which could be used to produce cellulosic biofuels mandated by the current Renewable Fuel Standard (RFS). This research integrates the Soil Water Assessment Tool (SWAT) watershed model and the DayCent biogeochemical model to investigate water quality and soil greenhouse gas flux that results when corn stover is collected at two different rates from corn-soybean and continuous corn crop rotations with and without tillage. Multiobjective watershed-scale optimizations are performed for individual pollutant-cost minimization criteria based on the economic cost of each cropping practice and (individually) the effect on nitrate, total phosphorus, sediment, or global warming potential. We compare these results with a purely economic optimization that maximizes stover production at the lowest cost without taking environmental impacts into account. We illustrate trade-offs between cost and different environmental performance criteria, assuming that nutrients contained in any stover collected must be replaced. The key finding is that stover collection using the practices modeled results in increased contributions to atmospheric greenhouse gases while reducing nitrate and total phosphorus loading to the watershed relative to the status quo without stover collection. Stover collection increases sediment loading to waterways relative to when no stover is removed for each crop rotation-tillage practice combination considered; no-till in combination with stover collection reduced sediment loading below baseline conditions without stover collection. Our results suggest that additional information is needed about (i) the level of nutrient replacement required to maintain grain yields and (ii) cost-effective management practices capable of reducing soil erosion when crop residues are removed in order to avoid contributions to climate change and water quality impairments as a result of using corn stover to satisfy the RFS.


Influence of maturation culture period on the development of canine oocytes after in vitro maturation and fertilization.
The objective of this study was to determine an optimum maturation period of canine oocytes for the development in vitro after in vitro fertilization (IVF). Canine oocytes larger than 110 micrometers in diameter, which were collected from ovaries at the follicular phase of the reproductive cycle, were cultured for each time (48, 72 and 96 h) in TCM 199 medium supplemented with 10% canine serum, fertilized, and then cultured in vitro for 8 days. Significantly more oocytes reached metaphase II (MII) in the 72-h culture group than in the 48-h culture group (25.6% vs. 41.0%). The percentages of oocytes that reached MII or beyond after maturation culture did not differ significantly between the 72- and 96-h culture groups, but the percentage of parthenogenetically activated oocytes in the 96-h culture group was significantly higher than that in the 72-h culture group. The percentages of cleaved embryos after IVF were significantly higher in the 48- and 72-h culture groups than in the 96-h culture group. In the 48-h culture group, 3.9% of fertilized oocytes developed to the 16-cell stage or beyond, but none of the cleaved embryos in the 72- and 96-h culture groups developed to the same stage. These results indicate that full nuclear maturation of oocytes collected from ovaries at the follicular phase occurs after 72 h of in vitro culture. However, an optimum maturation period (48 h) for the in vitro development of canine oocytes after IVF may be different from the period necessary to reach the maximal oocyte maturation rate, when based on the developmental stage of the cleaved embryos.