EGFR as a prognostic biomarker and therapeutic target in ovarian cancer: evaluation of patient cohort and literature review.
Limited effectiveness of therapeutic agents targeting epidermal growth factor receptor (EGFR) in clinical trials using unselected ovarian cancer patients has prompted efforts to more effectively stratify patients who might best benefit from these therapies. A series of studies that have evaluated immunohistochemical (IHC) staining of EGFR in ovarian cancer biopsies has produced unclear results as to the utility of this measure as a prognostic biomarker. Here, we used one of the largest, single institution cohorts to date to determine possible associations of EGFR expression with patient outcome. We performed IHC staining of EGFR in tissue microarrays including nearly 500 patient tumor samples. Staining was classified by subcellular localization (membranous, cytoplasmic) or by automated image analysis algorithms. We also performed a literature review to place these results in the context of previous studies. No significant associations were found between EGFR subcellular localization or expression and histology, stage, grade, or outcome. These results were broadly consistent with the consensus of the reviewed literature. These results suggest that IHC staining for EGFR may not be a useful prognostic biomarker for ovarian cancer patients. Future studies should pursue other staining methods or analysis in combination with other pathway mediators.


Gathering Trauma Narratives: A Qualitative Study on the Impact of Self-Identified Traumas on People Living with HIV (PLWH).
BACKGROUND Trauma-emotional, physical, and psychological-is common and associated with increased risk behaviors, low rates of care engagement and viral suppression, and overall poor health outcomes for people living with HIV (PLWH). This article presents the results of 15 in-depth, semi-structured interviews with PLWH in the Southeastern United States in which participants identified a trauma and described its long-lasting impact on their lives. Participants' trauma narratives described a wide range of traumas, including childhood sexual abuse, the loss of a loved one, and their HIV diagnosis.METHODS Systematic qualitative analysis was used to delineate beliefs about causes, symptoms, treatments, quality of life, and health implications of trauma.RESULTS: Fifteen participants completed semi-structured interviews that lasted on average 32 minutes. Participants described a wide spectrum of personal trauma that occurred both prior and subsequent to their HIV diagnosis. The types of trauma identified included physical, sexual, and psychological abuse inflicted by intimate partners, family members, and/or strangers.LIMITATIONS A chief limitation of this study is selection bias. Additionally, the participant selection and content of the trauma narratives might have been affected by the surrounding context of the parent study centered on HIV, aging, and psychosocial stress. It is also difficult to interpret the distinction between discrete trauma experiences and the diagnosis of HIV, leading to potential information bias.CONCLUSION This study highlights the importance of social support in coping with trauma and the effect of trauma on health-related behaviors. It also illustrates the need for additional research on the topic of trauma and trauma-informed care for PLWH. Understanding how different types of trauma affect individuals' lives is necessary to inform recommendations to provide better care for PLWH.


The impact of glottal area discontinuities on block-type vocal fold models with asymmetric tissue properties.
Block-type lumped-element models of the vocal folds are widely used for speech investigations due in part to the rich dynamics exhibited over a range of input parameters, particularly for asymmetric tissue properties. While self-consistent in derivation and application, block-type models of the vocal fold masses are inherently susceptible to non-physical aerodynamic loading conditions when vocal fold motion is highly asymmetric. A standard block-type model is compared against two modified models that disallow the non-physiological loading condition. These minor modifications toward a more physiologically relevant aerodynamic model alter the specific vibration regimes and prevalence of chaos, though bifurcations still exist.


Sample preparation for scanning electron microscopy of plant surfaces--horses for courses.
Plant tissues must be dehydrated for observation in most electron microscopes. Although a number of sample processing techniques have been developed for preserving plant tissues in their original form and structure, none of them are guaranteed artefact-free. The current paper reviews common scanning electron microscopy techniques and the sample preparation methods employed for visualisation of leaves under specific types of electron microscopes. Common artefacts introduced by specific techniques on different leaf types are discussed. Comparative examples are depicted from our lab using similar techniques; the pros and cons for specific techniques are discussed. New promising techniques and microscopes, which can alleviate some of the problems encountered in conventional methods of leaf sample processing and visualisation, are also discussed. It is concluded that the choice of technique for a specific leaf sample is dictated by the surface features that need to be preserved (such as trichomes, epidermal cells or wax microstructure), the resolution to be achieved, availability of the appropriate processing equipment and the technical capabilities of the available electron microscope.


Modification of biological activities of Ricinus communis agglutinin by cross-linking with formaldehyde.
Formaldehyde treatment of Ricinus communis agglutinin, a nonmitogenic toxic 120 000 molecular weight (MW) lectin, yielded two distinct protein fractions: one was heterogeneous and contained high molecular weight lectin polymers (greater than 120 000), and the other was a homogeneous 120 000 MW protein. Both fractions lost their cytotoxicity after formaldehyde treatment and stimulated thymidine incorporation into lymphocytes. Binding of both treated lectin fractions to lymphocytes exhibited positive cooperativity, whereas binding of untreated lectin did not.


Prognostic Value of the Leuko-Glycaemic Index in the Postoperative Period of Coronary Artery Bypass Grafting.
High leuko-glycaemic index (LGI) (> 2000) has been associated with poor prognosis in many critical care settings. However, there is no evidence of LGI's prognostic value in the postoperative period of coronary artery bypass grafting (CABG). This study aims to analyze the prognostic value of LGI in the postoperative period of CABG. Single-center retrospective analysis of prospectively collected data was performed. Consecutive adult patients undergoing CABG between 2007 and 2019 were included. Blood glucose levels and white blood cells count were evaluated in the immediate postoperative period. LGI was calculated by multiplying both values and dividing them by 1,000 and analyzed in quartiles. Receiver operating characteristic curve was used to determine the best cutoff value. The primary combined endpoint was in-hospital mortality, low cardiac output (LCO), or acute kidney injury (AKI). Secondary endpoints included in-hospital death, AKI, atrial fibrillation, and LCO. The study evaluated 3,813 patients undergoing CABG (88.5% male, 89.8% off-pump surgery, aged 64.6 years [standard deviation 9.6]). The median of LGI was 2,035. Presence of primary endpoint significantly increased per LGI quartile (9.2%, 9.7%, 11.8%, and 15%; P<0.001). High LGI was associated with increased occurrence of in-hospital mortality, LCO, AKI, and atrial fibrillation. The best prognostic cutoff value for primary endpoint was 2,000. In a multivariate logistic regression model, high LGI was independently associated with in-hospital death, LCO, or AKI. High LGI was an independent predictor of inhospital mortality, LCO, or AKI in postoperative period of CABG. It was also associated with higher in-hospital death.


Simulating CO₂ leakages from CCS to determine Zn toxicity using the marine microalgae Pleurochrysis roscoffensis.
Due to the current climate change and ocean acidification, a new technology for CO2 mitigation has been proposed, the Carbon dioxide Capture and Storage (CCS). However, there is an ecological risk associated with potential CO2 leakages from the sub-seabed storages sites. To evaluate the effects related to CO2 leakages, laboratory-scales experiments were performed using the marine microalgae Pleurochrysis roscoffensis. Five Zn concentrations were tested at different pHs to study Zn toxicity under acidified conditions. Seawater was collected and submitted to acidification by means of CO2 injection and by HCl addition. Results showed differences between both acidification techniques: while microalgae growth was enhanced by CO2 supply, reaching the optimal growth at pH 6.5 and full inhibition at pH 5.5, HCl acidification growth was inhibited at pH 6.5. Although small concentrations of Zn were positive for P. roscoffensis growth, Zn toxicity increased at lower pHs, and more severely on samples acidified with HCl. The conclusions obtained in this work are useful to address the potential effects on the marine ecosystem related to changes in metal bioavailability during CO2 leakages scenarios.


Reduction of Background Generated from Template-Template Hybridizations in the Exponential Amplification Reaction.
The Exponential Amplification Reaction (EXPAR) enables isothermal amplification of nucleic acids. However, applications of EXPAR for the amplification of trace amounts of nucleic acids are hindered by high background. The mechanism of background generation is currently not well understood, although it is assumed to involve nonspecific extension of EXPAR templates by DNA polymerase. We present here a study of the mechanisms of triggering EXPAR background amplification. We show that interactions of EXPAR templates lead to background amplification via polymerase extension of the templates. We further designed and tested two strategies to minimize background amplification: blocking of the 3'-end of the template and sequence-independent weakening of the template-template interactions. Sequence-specific 3'-end blocking showed reduced background, suggesting that 3'-end template interactions are a contributing factor to background amplification. Sequence-independent binding of the whole EXPAR template substantially reduced background amplification by competing with template-template interactions along the entire template sequence. This study provided evidence that nonspecific template interactions and extension by DNA polymerase triggered the amplification of background in EXPAR. The addition of single stranded binding protein to bind nonspecifically with the EXPAR template decreased background by 3 orders of magnitude.


Expression of Cationic Amino Acid Transporter 2 Is Required for Myeloid-Derived Suppressor Cell-Mediated Control of T Cell Immunity.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that expand during benign and cancer-associated inflammation and are characterized by their ability to inhibit T cell immunity. Increased metabolism of l-Arginine (l-Arg), through the enzymes arginase 1 and NO synthase 2 (NOS2), is well documented as a major MDSC suppressive mechanism. Therefore, we hypothesized that restricting MDSC uptake of l-Arg is a critical control point to modulate their suppressor activity. Using murine models of prostate-specific inflammation and cancer, we have identified the mechanisms by which extracellular l-Arg is transported into MDSCs. We have shown that MDSCs recruited to localized inflammation and tumor sites upregulate cationic amino acid transporter 2 (Cat2), coordinately with Arg1 and Nos2. Cat2 expression is not induced in MDSCs in peripheral organs. CAT2 contributes to the transport of l-Arg in MDSCs and is an important regulator of MDSC suppressive function. MDSCs that lack CAT2 have significantly reduced suppressive ability ex vivo and display impaired capacity for regulating T cell responses in vivo as evidenced by increased T cell expansion and decreased tumor growth in Cat2(-/-) mice. The abrogation of suppressive function is due to low intracellular l-Arg levels, which leads to the impaired ability of NOS2 to catalyze l-Arg-dependent metabolic processes. Together, these findings demonstrate that CAT2 modulates MDSC function. In the absence of CAT2, MDSCs display diminished capacity for controlling T cell immunity in prostate inflammation and cancer models, where the loss of CAT2 results in enhanced antitumor activity.


The association between job satisfaction and general health among employees of Golestan Hospital in Ahvaz, Iran.
Job satisfaction is one of the most challenging organizational concepts, and it is the basis of management policies to increase productivity and efficiency of the organization. The general health rate may affect job satisfaction in several ways. This study aimed to determine the association between job satisfaction and general health among employees of Golestan Hospital in Ahvaz, Iran. The study population of this cross-sectional research included 100 employees of Golestan Hospital in Ahvaz, Iran. The data collection instruments were the General Health Questionnaire (28-GHQ) and the Job Descriptive Index (JDI) questionnaire. The data were analyzed using Pearson's product-moment correlation coefficient, independent samples t-test, and ANOVA statistical tests in SPSS software. The mean general health was calculated as 26.19 ± 11.04, which indicated a positive psychiatric condition. Job satisfaction with a mean score of 89.67 ± 23.3 was deemed to be relatively dissatisfied. A medium negative and significant association was observed between job satisfaction and general health and its subscales (physical health, anxiety, social, and depression). General health subscales and job satisfaction are associated. Some actions must be planned to cope with the negative factors in general health in order to increase employees' satisfaction in university educational hospitals.


Pulmonary preneoplasia.
Improved screening techniques for lung cancer have resulted in detection of lesions that are considered to represent precursors of invasive lung carcinomas. These lesions may cause a diagnostic dilemma particularly on small biopsy or cytology specimens. Ancillary studies are usually not helpful, and diagnosis is based on morphology alone. Recognition of these lesions is very important to prevent potential diagnostic mistakes that may result in inadequate patient management. Future molecular studies may provide clinically useful diagnostic and prognostic gene markers. To review currently proposed morphologic criteria for precursor lesions of non-small cell lung carcinomas including squamous dysplasias, atypical adenomatous hyperplasia, and diffuse idiopathic neuroendocrine cell hyperplasia. Major molecular abnormalities are briefly discussed. Published literature and recent World Health Organization classification of lung tumors. Practicing surgical pathologists must be familiar with morphology of recognized pulmonary preneoplastic lesions that are more frequently detected radiographically and subjected to diagnostic procedures. Future understanding of underlying molecular abnormalities associated with progression of these lesions into invasive lung carcinoma may result in a development of molecular assays with potential diagnostic and prognostic importance.


Multi-dimensional wavepacket and potential reconstruction by resonant coherent anti-Stokes Raman scattering: application to H2O and HOD.
We have recently proposed a methodology for reconstructing excited-state (ExS) molecular wavepackets, and the corresponding potential energy surface, from three-pulse resonant coherent anti-Stokes Raman scattering and knowledge of the ground-state potential [Avisar and Tannor, Phys. Rev. Lett. 106, 170405 (2011)]. The methodology is general for polyatomics and applies to any form of ExS potential--bound or dissociative. In our previous work we demonstrated the method on diatomics. Here, we demonstrate the method on the triatomics H(2)O and HOD, reconstructing the ExS wavepacket and potential in the two bond-stretching coordinates.


Usability of the Clinical Care Classification System for Representing Nursing Practice According to Specialty.
This study examined the ability of the Clinical Care Classification system to represent nursing record data across various nursing specialties. The data comprised nursing care plan records from December 1998 to October 2008 in a medical center. The total number of care plan documentation we analyzed was 2 060 178, and we used a process of knowledge discovery in datasets for data analysis. The results showed that 75.42% of the documented diagnosis terms could be mapped using the Clinical Care Classification system. However, a difference in nursing terminology emerged among various nursing specialties, ranging from 0.1% for otorhinolaryngology to 100% for colorectal surgery and plastic surgery. The top five nursing diagnoses were identified as knowledge deficit, acute pain, infection risk, falling risk, and bleeding risk, which were the most common health problems in an acute care setting but not in non-acute care settings. Overall, we identified a total of 21 established nursing diagnoses, which we recommend adding to the Clinical Care Classification system, most of which are applicable to emergency and intensive care specialties. Our results show that Clinical Care Classification is useful for documenting patient's problems in an acute setting, but we suggest adding new diagnoses to identify health problems in specialty settings.


Hemodynamic changes with enalapril in pulmonary arterial hypertension secondary to congenital heart disease.
Enalapril was used to treat five patients with pulmonary arterial hypertension secondary to congenital cardiopathy, three with ventricular septal defect, one with arterial septal defect, and one with patent ductus arteriosus. The dose of enalapril was 20 mg/day. All patients underwent pretreatment and posttreatment cardiac catheterization. It was concluded that enalapril may be a useful drug in the treatment of pulmonary arterial hypertension secondary to congenital cardiopathy.


Stronger Microstructural Damage Revealed in Multiple Sclerosis Lesions With Central Vein Sign by Quantitative Gradient Echo MRI.
Multiple sclerosis (MS) lesions typically form around a central vein that can be visualized with FLAIR* MRI, creating the central vein sign (CVS) which may reflect lesion pathophysiology. Herein we used gradient echo plural contrast imaging (GEPCI) MRI to simultaneously visualize CVS and measure tissue damage in MS lesions. We examined CVS in relation to tissue integrity in white matter (WM) lesions and among MS subtypes. We aimed to determine if CVS positive lesions were specific to MS subtype, if CVS can be detected consistently among readers using the GEPCI method, and if there were differences in tissue damage in lesions with vs without CVS. Thirty relapsing-remitting MS (RRMS) subjects and 38 primary and secondary progressive MS (PMS) subjects were scanned with GEPCI protocol at 3T. GEPCI T2*-SWI images were generated to visualize CVS. Two investigators independently evaluated WM lesions for CVS and measured lesion volumes. To estimate tissue damage severity, total lesion volume, and mean lesion volume, R2t*-based tissue damage score (TDS) of individual lesions and tissue damage load (TDL) were measured for CVS+, CVS-, and confluent lesions. Spearman correlations were made between MRI and clinical data. One-way ANCOVA with age and sex as covariates was used to compare measurements of CVS+ vs CVS- lesions in each individual. 398 of 548 lesions meeting inclusion criteria showed CVS. Most patients had ≥40% CVS+ lesions. CVS+ lesions were present in similar proportion among MS subtypes. Interobserver agreement was high for CVS detection. CVS+ and confluent lesions had higher average and total volumes vs CVS- lesions. CVS+ and confluent lesions had more tissue damage than CVS- lesions based on TDL and mean TDS. CVS occurred in RRMS and PMS in similar proportions. CVS+ lesions had greater tissue damage and larger size than CVS- lesions.


The 5-Me of thyminyl (T) interaction with the neighboring nucleobases dictate the relative stability of isosequential DNA-RNA hybrid duplexes.
Relative energetic contributions from the base-pairing [DeltaG(degrees)(bp)] vis-a-vis stacking [DeltaG(degrees)(stacking)] to the total free-energy of stabilization [DeltaG(degrees)(37)] for 14 pairs of isosequential hybrid DNA-RNA duplexes (taken from E. A. Lesnik and S. M. Freier, Biochemistry ,1995, 34, 10807) have been dissected in order to understand the differences in the intrinsic nature of the electrostatic forces that are responsible for the self-assembly of the heteroduplexes compared to homoduplexes. The pKa differences between the monomeric nucleotide 3'-ethylphosphates [(d/rN)pEt] as well as nucleotide 3',5'-bis-ethylphosphates [Etp(d/rN)pEt] in both 2'-deoxy (dN) and ribo (rN) series (N = A/G/C/T/U), as the model donor and acceptor (in which stacking is completely eliminated) mimicking those of the internucleotide monomer building blocks of a duplex, can be qualitatively used (P. Acharya, P. Cheruku, S. Chatterjee, S. Acharya and J. Chattopadhyaya, J. Am. Chem. Soc., 2004, 126, 2862) to understand the strength of base-pairing energies in different DNA-RNA (DR), RNA-DNA (RD), DNA-DNA (DD), and RNA-RNA (RR) duplexes. The study has led us to show the following. (1) As the number of excess %T in DR duplexes compared to the isosequential RD duplexes increase the differences in their thermal stabilization [DeltaT(m)](DR-RD) increase and vice-versa(2) The total relative stabilizations, [DeltaDeltaG(degrees)(37)](DR-RD) among the 14 pairs of isosequential DR and RD duplexes (E. A. Lesnik and S. M. Freier, Biochemistry ,1995, 34, 10807) are wholly dependent on the differences in the number of 5-Me(T) stacking interactions with the nearest-neighbors in the D strands of DR duplexes compared to that of the RD duplexes (3) In the relative stabilization of the DR or RD duplexes differences in the free-energy of stackings [DeltaDeltaG(degrees)(stacking)](DR-RD) play a more significant role than the differences in the free-energy of base-pairing, [DeltaDeltaG(degrees)(bp)](DR-RD). In contradistinction, our experimental data shows that RNA-RNA duplexes are more stable than DNA-DNA duplexes because of larger energy gain from the base-pairing in the former compared to the latter (P. Acharya, P. Cheruku, S. Chatterjee, S. Acharya and J. Chattopadhyaya, J. Am. Chem. Soc., 2004, 126, 2862).


Anesthetic experience in patient for single lung transplantation with previous contralateral pneumonectomy -A case report-.
A 48-year-old woman with cystic fibrosis and a previous left pneumonectomy had surgery planned for single lung transplantation under general anesthesia. Due to progressive dyspnea and recurrent respiratory infection, she could not maintain her normal daily life without lung transplantation. The anesthetic management and surgical procedure was expected to be difficult because of the left mediastinal shift and an asymmetric thorax after the left pneumonectomy, but the single lung transplantation was successfully done under cardiopulmonary bypass.


Genetic analysis of human complement factor H polymorphisms.
Human complement factor H (factor H) is polymorphic, with five previously reported FH alleles and three previously reported HF alleles (HF*A, HF*B, and HF*Q0). The relationship between the FH and HF alleles is not clear, and the genetic basis of factor H phenotypes has not yet been identified. In this study, nucleotide sequence analysis of complementary DNA (cDNA) from individuals with each HF phenotype identified seven mutated sites in the factor H gene. However, in four cases, the same cDNA sequence was observed in individuals with two different HF phenotypes. Western blotting and 2-DE also showed that a 160 kDa protein corresponding to factor H was expressed in individuals with HF phenotypes. In addition, factor H cross-reacting 45 and 42 kDa polypeptides were detected in individuals with HF A, HF B, or HF AB phenotypes, but not in individuals with the HF Q0 (a null allele) phenotype. Thus, HF phenotype did not correlate well with factor H gene or protein structural variation. Evidence is provided to support the hypothesis that the HF phenotypes do not correspond to polymorphism in factor H, but instead correspond to polymorphism in factor H-related protein 1. A novel PCR-RFLP method was developed and used to detect four polymorphisms (G257A, G1492A, A2089G, and G2881T) in the factor H gene in 54 unrelated Japanese individuals. This method could be useful for studies on genetic disease associated with these mutations.


Single-cell profiling of transcriptome and histone modifications with EpiDamID.
Recent advances in single-cell sequencing technologies have enabled simultaneous measurement of multiple cellular modalities, but the combined detection of histone post-translational modifications and transcription at single-cell resolution has remained limited. Here, we introduce EpiDamID, an experimental approach to target a diverse set of chromatin types by leveraging the binding specificities of single-chain variable fragment antibodies, engineered chromatin reader domains, and endogenous chromatin-binding proteins. Using these, we render the DamID technology compatible with the genome-wide identification of histone post-translational modifications. Importantly, this includes the possibility to jointly measure chromatin marks and transcription at the single-cell level. We use EpiDamID to profile single-cell Polycomb occupancy in mouse embryoid bodies and provide evidence for hierarchical gene regulatory networks. In addition, we map H3K9me3 in early zebrafish embryogenesis, and detect striking heterochromatic regions specific to notochord. Overall, EpiDamID is a new addition to a vast toolbox to study chromatin states during dynamic cellular processes.


Systemic hypoxia enhances bactericidal activities of human polymorphonuclear leuocytes.
ROS (reactive oxygen species) generated by hypoxia facilitate the vascular inflammatory response, but whether systemic hypoxia influences leucocyte bactericidal activity by modulating circulatory redox status remains unclear. The present study elucidates how various hypoxic interventions influence the bactericidal activity of PMNs (polymorphonuclear leucocytes) following treatment with an antioxidant, vitamin E (D-alpha-tocopheryl acetate). Forty healthy sedentary men were randomly assigned to vitamin E (n=20) and placebo (n=20) groups. At 1 h following oral administration of 1000 i.u. of vitamin E or placebo, each subject in the two groups was randomly exposed to 12%, 15%, 18% and 21% O2 for 2 h in a normobaric hypoxia chamber. The results demonstrated that exposure to 12% O2 in the placebo group increased urinary 8-isoprostane and plasma malondialdehyde levels and decreased plasma total antioxidant content and superoxide dismutase activity, but did not alter plasma complement-C3a desArg/C4a desArg/C5a concentrations. Moreover, this hypoxic exposure also increased the chemotaxis of PMNs by exposure to N-formyl-Met-Leu-Phe, the phagocytosis of PMNs to Escherichia coli and the release of PMN oxidant products by E. coli, processes which were accompanied by increased expressions of L-selectin, LFA-1 (lymphocyte function-associated antigen 1), Mac-1, FcgammaIIIBR, C1qRp and C5aR on PMNs. However, exposure to 12% O2 in the vitamin E group did not influence expression of the opsonic/complement receptors on PMNs, and the chemotactic, phagocytic or oxidative burst activities of PMN, whereas the circulatory redox status and complement fragment levels were unaltered following this hypoxic exposure and pretreatment with vitamin E. Additionally, the circulatory redox status, complement systems, PMN-mediated bactericidal processes and the opsonic/complement receptors on PMNs were constant following exposure to 15%, 18% or 21% O2 in the two groups. We conclude that exposure to 12% O2 promotes the chemotactic, phagocytic and oxidative burst activities of PMNs, possibly by increasing lipid peroxidation and decreasing antioxidative capacity. However, this hypoxic effect on PMN bactericidal activity is ameliorated by pretreatment with vitamin E.


Effect of using cardiovascular risk scoring in routine risk assessment in primary prevention of cardiovascular disease: protocol for an overview of systematic reviews.
Major clinical practice guidelines recommend assessing risk of cardiovascular disease (CVD) using absolute/global/total CVD risk scores. However, the effectiveness of using them in clinical practice, despite publication of numerous randomised controlled trials (RCTs), is still poorly understood. To summarise and analyse current knowledge in this field, we will carry out an overview of existing systematic reviews (SRs). The objective of this overview will be to assess the effect of using cardiovascular risk scoring in routine risk assessment in primary prevention of CVD compared with standard care. We will include SRs and meta-analyses which take into account RCTs and quasi-RCTs investigating the effect of using cardiovascular risk scoring in routine risk assessment in primary prevention of CVD. SRs will be retrieved from 4 bibliographical databases and reference lists of identified reviews. Additionally, the PROSPERO database will be searched for unpublished, ongoing or recently completed SRs. 2 reviewers will assess the SRs independently for eligibility and bias. The data will be extracted to a special form. Any disagreement will be resolved by discussion. In case of lack of consensus, a third author will arbitrate. The overview of SRs will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Ethics approval is not required for overview of SRs. We will summarise evidence concerning whether use of the absolute/global/total CVD risk scoring tools in primary prevention of CVD is effective and supported with scientific data or not. If we face unsatisfactory confirmation, we will highlight a need for further research and advice on how to plan such a study. We will submit the results of our study for peer-review publication in a journal indexed in the international bibliographic database of biomedical information.


Vasomotor rhinitis: neglected cause of nasal congestion.
Vasomotor rhinitis is a condition of chronic nasal congestion which is noninfectious and nonallergic. Its cause is thought to be an imbalance of autonomic control to the nasal mucosa. This disorder is a diagnosis of exclusion, and other causes of chronic nasal obstruction must be considered first. Treatment measures include avoidance of nonspecific stimuli which exacerbate symptoms and, for symptomatic relief, use of oral sympathomimetics. Antihistamine-decongestant combinations may be effective in some patients. Topical vasoconstrictors should not be used.


Role of Music in a Plastic Surgery Setting: A Systematic Review and Meta-analysis.
Objective To assess the effectiveness and harm of music to reduce anxiety and pain in a plastic surgery setting. Materials and Methods A search strategy was conducted in the MEDLINE, CENTRAL, EMBASE, and LILACS databases. Searches were also conducted in other databases and unpublished literature. Clinical trials were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. An analysis of random effects was conducted. The primary outcomes were anxiety and pain. The secondary outcomes were length of stay, physiological parameters, and adverse effects. The measure of the effect was the mean difference (MD) and standardized MD (SMD) with a 95% confidence interval (CI). The planned interventions were music versus no music. Results Four articles were included in the qualitative and quantitative analysis. A total of 306 patients were found among the four studies. A low risk of bias was shown for most of the study items. The overall standardized mean difference (SMD) for anxiety -3.64 [95%CI -5.71 to -1.56 (p-value = 0.0006)] favoring music compared with no intervention, and for pain the mean difference (MD) was -12.06 [95%CI -33.47 to 9.35 (p-value = 0.2696)] showing no statistical differences. Conclusion Playing music is a safe and free intervention that diminishes anxiety in patients who undergo plastic surgery procedures.


[Development of intravital bone tissue imaging and future perspectives of new lines of therapies for bone diseases.]
Recent advances in live imaging technology for 'seeing the unseen' phenomenon has been so enormous to revolutionize the diverse fields of biomedical sciences. We have so far pioneered to exploit the technique into the analyses of live bone tissues and made it possible to detect dynamic movements of single cells and multicellular interaction in intact bone tissues. Now that the cutting-edge techniques have been matured enough, we can also utilize this for validation of pharmacological actions in various regimens in vivo as well as for novel drug discovery for treating against bone diseases. In this brief review, I describe the overview of the studies related to intravital bone imaging and its application and contribution for future medicine in this field.


Cannabinoid CB1 receptor dependent effects of the NMDA antagonist phencyclidine in the social withdrawal model of schizophrenia.
Clinical and laboratory findings suggest that cannabinoid signalling is implicated in schizophrenia. However, the interaction remains poorly understood, as data are often contradictory. Here we investigated wild-type (WT) and cannabinoid CB1 receptor-knockout (CB1-KO) mice in the phencyclidine-induced social withdrawal model of schizophrenia. N-methyl-D-aspartate (NMDA) antagonists (including phencyclidine) induce psychotic symptoms in humans, and are used to model schizophrenia in a variety of experimental conditions. In WTs, 5 mg/kg phencyclidine increased locomotion and stereotyped behaviours, and decreased social interactions. These changes are consistent with a schizophrenia-like effect. In CB1-KOs, phencyclidine decreased locomotion, enhanced ataxia and stereotypy more markedly than in WTs, but did not affect social interactions. Locomotion showed a significant negative correlation with both ataxia and stereotypy, suggesting that in CB1-KOs, the locomotor suppressive effect of phencyclidine was secondary to changes in these variables. Our findings demonstrate that CB1 gene disruption dramatically alters the behavioural effects of the NMDA antagonist phencyclidine, suggesting that the CB1 receptor is involved in schizophrenia. As social disruption and stereotypy respectively are believed to model negative and positive symptoms of schizophrenia, our findings tentatively suggest that cannabinoids are differentially involved in these two symptom categories. These findings require verification by experiments involving CB1 receptor blockers, as the genetic and pharmacological blockade of receptors may not always provide similar results.


Survey of maximum CTG/CAG repeat lengths in humans and non-human primates: total genome scan in populations using the Repeat Expansion Detection method.
Repeat Expansion Detection (RED) is an efficient and simple method for detecting repeat expansions in the human genome, including expansion mutations resulting in disease. Here we report the first population survey of CTG/CAG repeat lengths in humans using the RED method; we have determined maximum CTG/CAG repeat length in 244 individuals from six human populations: Danes, Chinese, Japanese, Rondonian Surui, Maya and Mbuti/Biaka Pygmies. We have also sampled a number of non-human primates including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees (Pan troglodytes) and three Hylobatidae (one Hylobates lar, one H.klossii, and one H.syndactylus). Our results demonstrate the existence of significant variation in the sizes and frequencies of the longest CTG/CAG repeat length seen per individual both within and between human populations. The population differences argue that overall mutation rates at CTG/CAG repeat loci are sufficiently low that mutation does not obliterate the effect of random genetic drift and clearly indicate that population stratification could occur in disease association studies using the RED method. No significant differences were detected among the non-human primates sampled. Our results also show that both common chimpanzees and pygmy chimpanzees (bonobos) are polymorphic for maximum length of any CTG/CAG repeats while no variation was found for gorillas and orang-utans.


Splenic rupture following endoscopic polypectomy.
A 70-year-old man presented with two medium-sized colon polyps at the office of a gastroenterologist. After endoscopic polypectomy in a hospital, the patient was admitted to another hospital because of collapse and increasing abdominal pain. CT scan revealed hematoperitoneum and splenic subcapsular hematoma. Laparotomy with splenectomy was performed because of extended splenic rupture. The postoperative course was unremarkable except late wound dehiscence.


Folate, homocysteine and the cardiac neural crest.
Congenital heart defects (CHD) are the most common congenital defects worldwide, and perigestational folate supplementation (PFS) is the most effective large-scale intervention to date for reducing CHD. This review is based upon the following premises: that the majority of CHD result from disruption of development of the cardiac neural crest (CNC); and that the CNC is highly responsive to folate and homocysteine. The following roles of folate are discussed in relation to CNC development: one-carbon metabolism in support of mitosis and gene methylation; and gene regulation via direct activity of the folate receptor. The following roles of hyperhomocysteinemia are discussed in the same context: increased oxidative stress; disruption of gene methylation; homocysteinylation of key proteins; and NMDA receptor binding. It is proposed that well-focused advances in folate-CNC research could lead to development of strategies, in addition to PFS, to facilitate normal CNC and heart development, and thereby further reduce CHD.


Executive function as a mediator in the link between single or complex trauma and posttraumatic stress in children and adolescents.
In this study, we examined whether there is a mediating role of executive function (EF) in the relationship between trauma exposure and posttraumatic stress in youth. Children and adolescents exposed to trauma were recruited at an academic center for child psychiatry in The Netherlands. The total sample consisted of 119 children from 9 to 17 years old (M = 13.65, SD = 2.45). Based on retrospective life event information, the sample was divided into three groups: a single trauma group (n = 41), a complex trauma group (n = 38), and a control group that was not exposed to traumatic events (n = 40). Our findings revealed that youth exposed to complex trauma had more deficits in EF compared to youth in the single trauma and control groups. EF was found to partly mediate posttraumatic stress symptoms for youth exposed to complex trauma, but not for youth exposed to single trauma. Youth exposed to complex trauma showed more deficits in EF, which was in turn associated with higher levels of posttraumatic stress symptoms. Our findings provide partial support for the role of EF in mediating posttraumatic stress outcomes for youth exposed to complex trauma. This points to the important role of EF in the etiology and treatment of complexly traumatized youth.


Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.
Allosteric peptide inhibitors of thymidylate synthase (hTS) bind to the dimer interface and stabilize the inactive form of the protein. Four interface residues were mutated to alanine, and interaction studies were employed to decode the key role of these residues in the peptide molecular recognition. This led to the identification of three crucial interface residues F59, L198, and Y202 that impart activity to the peptide inhibitors and suggest the binding area for further inhibitor design.


Development and validation of monoclonal and polyclonal antibodies for the detection of immunoglobulin G of bottlenose dolphins (Tursiops truncatus).
Antibodies directed against species-specific immunoglobulin G (IgG) have a broad range of applications in serologic and immunologic research and in the development of clinical assays. Validated anti-IgG antibodies for marine mammal species are in short supply. The objective of this study was to produce and validate antibodies with specificity for IgG of the common bottlenose dolphin (Tursiops truncatus). Bottlenose dolphin IgG was purified using protein G. Two mouse monoclonal antibodies and a rabbit polyclonal antibody were developed from mice and rabbits immunized with bottlenose dolphin IgG. The specificity of the monoclonal antibodies and the polyclonal antibody for bottlenose dolphin IgG was first verified by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). For further validation, both monoclonal antibodies and the polyclonal antibody were incorporated in an indirect ELISA for the detection of the immune response of bottlenose dolphins to a vaccine antigen. Three bottlenose dolphins were immunized with a commercial Erysipelothrix rhusiopathiae vaccine, and serial blood samples were collected from all dolphins for measurement of levels of circulating antibodies. Seroconversion was observed in all 3 dolphins by use of both monoclonal antibodies and the polyclonal antibody. Circulating antibodies were detectable as early as 6 days after immunization in 1 dolphin. Peak antibody levels were detected 14 days after the immunization. The ability to detect seroconversion in all 3 immunized bottlenose dolphins firmly establishes the specificity of the monoclonal antibodies and the polyclonal antibody for IgG of the common bottlenose dolphin.


1H Nuclear Magnetic Resonance (NMR)-Based Cerebrospinal Fluid and Plasma Metabolomic Analysis in Type 2 Diabetic Patients and Risk Prediction for Diabetic Microangiopathy.
Insulin resistance and metabolic derangement are present in patients with type 2 diabetes mellitus (T2DM). However, the metabolomic signature of T2DM in cerebrospinal fluid (CSF) has not been investigated thus far. In this prospective metabolomic study, fasting CSF and plasma samples from 40 T2DM patients to 36 control subjects undergoing elective surgery with spinal anesthesia were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy. NMR spectra of CSF and plasma metabolites were analyzed and correlated with the presence of T2DM and diabetic microangiopathy (retinopathy, nephropathy, and neuropathy) using an area under the curve (AUC) estimation. CSF metabolomic profiles in T2DM patients vs. controls revealed significantly increased levels of alanine, leucine, valine, tyrosine, lactate, pyruvate, and decreased levels of histidine. In addition, a combination of alanine, histidine, leucine, pyruvate, tyrosine, and valine in CSF showed a superior correlation with the presence of T2DM (AUC:0.951), diabetic retinopathy (AUC:0.858), nephropathy (AUC:0.811), and neuropathy (AUC:0.691). Similar correlations also appeared in plasma profiling. These metabolic alterations in CSF suggest decreasing aerobic metabolism and increasing anaerobic glycolysis in cerebral circulation of patients with T2DM. In conclusion, our results provide clues for the metabolic derangements in diabetic central neuropathy among T2DM patients; however, their clinical significance requires further exploration.


Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone.
The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.


Prospective evaluation of the acute patient physiologic and laboratory evaluation score and an extended clinicopathological profile in dogs with systemic inflammatory response syndrome.
To investigate the prognostic value of the acute patient physiologic and laboratory evaluation (APPLE) score and relevant clinicopathological markers in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational cohort study. Veterinary teaching hospital. Thirty-three dogs with SIRS admitted to the intensive care unit (ICU) were compared to 35 healthy control dogs. Dogs with SIRS were divided into septic (n = 20) and nonseptic (n = 13) etiologies and as survivors (alive to discharge, n = 22) and nonsurvivors (n = 11: died, n = 6, or humanely euthanized, n = 5). For all dogs, physiological and laboratory parameters were prospectively collected for the calculation of the APPLE fast score. No difference between septic and nonseptic SIRS dogs was detected for any parameter evaluated. Survivors had significantly higher total protein, albumin concentrations, antithrombin activity (ATA), and base excess (BE), as well as significantly lower lactate, urea, creatinine concentrations, urinary protein to creatinine ratio and APPLE fast score compared to nonsurvivors. Higher values of creatinine, lactate, anion gap, alanine transaminase (ALT), and APPLE fast score were significantly associated with an increased risk of death in SIRS dogs, while higher values of total protein, albumin, ATA, and BE were associated with a significantly reduced risk of mortality. When a multivariate binary logistic regression analysis was performed, the APPLE fast score was the only significant parameter retained. The determination of the APPLE fast score in clinical setting, as well as the measurement of APP, ATA, lactate, BE, anion gap, ALT, urinary proteins, and electrolytes may be beneficial for a better assessment of dogs with SIRS. Identified parameters were significantly related with the presence of SIRS and their evaluation should be considered for the assessment of disease severity, and guidance of the decision-making process in critically ill dogs.


Mechanism of pathogenesis of imiquimod-induced skin inflammation in the mouse: a role for interferon-alpha in dendritic cell activation by imiquimod.
Topical application of imiquimod (IMQ), a Toll-like receptor (TLR)7 ligand, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. In a mouse model of IMQ-induced psoriasis-like skin inflammation, T-helper (Th)17 cells and interleukin (IL)-17/IL-22-producing γδ-T cells have been shown to play a pivotal role. However, the mechanisms of induction of the Th17 pathway and development of psoriasis-like skin inflammation by IMQ treatment remain unclear. In this study, we investigated pathogenic mechanisms of IMQ-induced psoriasis-like skin inflammation in mice. We first confirmed that, together with an increase in IL-17 and IL-22 production, application of IMQ to mouse skin induced the expression of cytokines required for activation of the Th17 pathway, and pro-inflammatory mediators involved in the pathology of psoriasis. Analysis of Tlr7(-/-) mice demonstrated that most of the in vivo effects of IMQ were mediated via TLR7. In an in vitro study using plasmacytoid dendritic cells (DCs), IMQ induced production of interferon (IFN)-α, IL-23, IL-6 and tumor necrosis factor (TNF)-α. Furthermore, when we analyzed in vitro-generated bone marrow-derived DCs with features similar to TNF-α and inducible nitric oxide synthase (iNOS)-producing DCs, IL-23, IL-6, IL-1β, TNF-α and iNOS/NO production was weakly induced by IMQ alone and further enhanced after co-stimulation with IMQ and IFN-α. These in vitro effects of IMQ were also mediated via TLR7 and the synergistic effect of IMQ, and IFN-α was suggested to be caused by upregulation of TLR7 expression by IFN-α. These results demonstrate part of the mechanism by which the Th17 pathway and psoriasis-like skin inflammation are induced by IMQ and IFN-α in a mouse model.


Ionizing radiation predisposes nonmalignant human mammary epithelial cells to undergo transforming growth factor beta induced epithelial to mesenchymal transition.
Transforming growth factor beta1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Nonmalignant HMEC (MCF10A, HMT3522 S1, and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture or treated with a low concentration of TGFbeta (0.4 ng/mL) or double treated. All double-treated (IR + TGFbeta) HMEC underwent a morphologic shift from cuboidal to spindle shaped. This phenotype was accompanied by a decreased expression of epithelial markers E-cadherin, beta-catenin, and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin, and vimentin. Furthermore, double treatment increased cell motility, promoted invasion, and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, although IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double-treated cells exhibit a specific 10-gene signature associated with Erk/mitogen-activated protein kinase (MAPK) signaling. We hypothesized that IR-induced MAPK activation primes nonmalignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation was transiently induced by irradiation and persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a MAP/Erk kinase (MEK) inhibitor, blocked the EMT phenotype. Together, these data show that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.


Mating affects egg maturation in Anopheles gambiae Giles (Diptera: Culicidae).
The effect of mating on egg development and the size of the female accessory glands during the gonotrophic cycle of Anopheles gambiae was investigated. Although females that received a measured meal of blood were more likely to produce an egg batch when they were mated, the increased reproduction was not the result of male accessory gland substances. Changes in the size of the female accessory gland were not observed after mating nor at any time during the gonotrophic cycle, but there was a more rapid increase in its size following emergence in mated females.


Pseudomonas folliculitis.
Previous reports of Pseudomonas folliculitis in children identified heated pools, hot tubs or spa baths as the source of the infection. This report presents a 4-year-old female with Pseudomonas folliculitis acquired from the family bath tub. The source of the infection was contaminated bath toys and bath plug.


CNAsim: improved simulation of single-cell copy number profiles and DNA-seq data from tumors.
CNAsim is a software package for improved simulation of single-cell copy number alteration (CNA) data from tumors. CNAsim can be used to efficiently generate single-cell copy number profiles for thousands of simulated tumor cells under a more realistic error model and a broader range of possible CNA mechanisms compared with existing simulators. The error model implemented in CNAsim accounts for the specific biases of single-cell sequencing that leads to read count fluctuation and poor resolution of CNA detection. For improved realism over existing simulators, CNAsim can (i) generate WGD, whole-chromosomal CNAs, and chromosome-arm CNAs, (ii) simulate subclonal population structure defined by the accumulation of chromosomal CNAs, and (iii) dilute the sampled cell population with both normal diploid cells and pseudo-diploid cells. The software can also generate DNA-seq data for sampled cells. CNAsim is written in Python and is freely available open-source from https://github.com/samsonweiner/CNAsim.


HIF2α/EFEMP1 cascade mediates hypoxic effects on breast cancer stem cell hierarchy.
Breast cancer stem cells (BCSCs) have been shown to contribute to tumor growth, metastasis, and recurrence. They are also markedly resistant to conventional cancer treatments, such as chemotherapy and radiation. Recent studies have suggested that hypoxia is one of the prominent micro-environmental factors that increase the self-renewal ability of BCSCs, partially by enhancing CSC phenotypes. Thus, the identification and development of new therapeutic approaches based on targeting the hypoxia-dependent responses in BCSCs is urgent. Through various in vitro studies, we found that hypoxia specifically up-regulates BCSC sphere formation and a subset of CD44+/CD24-/low CSCs. Hypoxia inducible factors 2α (HIF2α) depletion suppressed CSC-like phenotypes and CSC-mediated drug resistance in breast cancer. Furthermore, the stimulatory effects of hypoxia-induced HIF2α on BCSC sphere formation were successfully attenuated by epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) knockdown. Taken together, these data suggest that HIF2α mediates hypoxia-induced cancer growth/metastasis and that EFEMP1 is a downstream effector of hypoxia-induced HIF2α during breast tumorigenesis.


Synergistic immunoprotection by Oma87 and Bap against Acinetobacter baumannii sepsis model.
Acinetobacter baumannii is the leading cause of nosocomial infection. A surface protein commonly known as biofilm associate protein (Bap) has been identified in a bloodstream isolate of A. baumannii. Bap of A. baumannii is involved in intercellular adhesion within the mature biofilm. Outer membrane protein Acinetobacter 87 kDa (Oma87) or β-barrel assembly machinery A (BamA) has been introduced as an immunogenic outer membrane protein via in silico reverse vaccinology. Current research examines the synergistic effect of immunization of mice with both recombinant proteins viz., Oma87 and Bap. Antibodies were raised to the proteins. The mice were challenged with A. baumannii ATCC 19606 and the bacterial burden was enumerated in the mice's livers, spleens, and lungs followed by histological examination. IgG levels significantly increased, and a significant (p < 0.0001) difference was observed between bacterial burdens in the internal organs of the actively and passively immunized groups. Female BALB/c mice weighing 20-25 g, were divided into 4 groups of 14 mice each viz., control, Oma87, Bap, Oma87-Bap groups. The proteins were individually immunogenic, but the combination of both proteins had a synergistic protection property. This is further supported by the histological examination. Based on the results, the combination of Oma87 and Bap may be considered a promising vaccine candidate against A. baumannii .


[Hepatocellular carcinoma associated to porphyria cutanea tarda and hepatitis C virus infection without cirrhosis].
The molecular basis of porphyria cutanea tarda is defective activity of hepatic uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C virus markers has been demonstrated. We study a patient with PCT and hepatitis C virus markers that finally develops to hepatocellular carcinoma without previous cirrhosis. Previous studies with association of PCT and hepatitis C virus markers, have found liver diseases ranging from cirrhosis to hepatocellular carcinoma. The importance of this study is the absence of cirrhosis.


Eosinophilic esophagitis: an interdisciplinary clinical problem.
Eosinophilic esophagitis is a newly described entity of increasing incidence. Previously thought to be a variation of gastroesophageal reflux disease, now it becomes well known among gastroenterologists, allergologists, paediatricians and pathologists. Aetiology of the disease is strongly correlated with atopic and allergic disorders but exact pathogenesis and cellular mechanisms of inflammatory process in the esophagus are still unknown. Diagnostic criteria have been described but diagnostic tools are still in the research and improvement phase. Clinical manifestation varies considerably between age groups, which causes a delay in the course of diagnosis due to improperly recognized symptoms. Since eosinophilic esophagitis is a chronic disease without a tendency to be self-limiting, delayed diagnosis may lead to complications associated with oesophageal tissue remodelling. Some forms of treatment are approved and of great therapeutical value, nevertheless clinical trials of new medications provide new possibilities. Therefore, many questions regarding eosinophilic esophagitis arise and are still unanswered.


Integrative invasion science: model systems, multi-site studies, focused meta-analysis and invasion syndromes.
Invasion science is a very active subdiscipline of ecology. However, some scientists contend that theoretical integration has been limited and that predictive power remains weak. This paper, focusing on plants, proposes a new multi-pronged research strategy that builds on recent advances in invasion science. More intensive studies on particular model organisms and ecosystems are needed to improve our understanding of the full suite of interacting factors that influence invasions ('model system research'). At the same time, comparative studies across many study systems are essential for unravelling the context-dependencies of insights that emerge from particular studies ('multi-site studies'); and quantitative synthesis based on large datasets should be constrained to well-defined theoretical domains ('focused meta-analysis'). We also suggest ways for better integration of information about species biology and ecosystem characteristics ('invasion syndromes'). We expect that a resulting theory of invasions will need to be conceived as a somewhat heterogeneous conglomerate of elements of varying generality and predictive power: laws that apply to well-specified domains, general concepts and theoretical frameworks that can guide thinking in research and management, and in-depth knowledge about the drivers of particular invasions.


Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation.
To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life (QOL) in patients after allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020. They completed two questionnaires: the Ocular Surface Disease Index (OSDI) and the quality-of-life scale for Chinese patients with visual impairment (SQOL-DV1). Ocular conditions and systemic conditions were also assessed. Eye damage was correlated with total bilirubin (P=0.005), and gamma-glutamyl transferase (GGT) (P=0.021). There was no significant correlation between the overall QOL score and OSDI (P=0.8226) or SQOL-DV1 (P=0.9526) scores. The OSDI and the overall QOL score were not correlated with ocular conditions, including best-corrected visual acuity (BCVA), intraocular pressure, Schirmer tear test II, sodium fluorescein staining, tear film breakup time, and tear meniscus height. SQOL-DV1 was correlated with BCVA (P=0.0007), sodium fluorescein staining (P=0.007), and tear film breakup time (P=0.0146). In some patients, early ocular symptoms are not evident after ALLO-HSCT, while ocular surface complications can be observed after a comprehensive ophthalmological examination. Especially for those with elevated total bilirubin or GGT, regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease (oGVHD), especially for patients with elevated total bilirubin or GGT.


Land use change analysis in the Zhujiang Delta of China using satellite remote sensing, GIS and stochastic modelling.
Rapid land use change has taken place in many coastal regions of China such as the Zhujiang Delta over the past two decades due to accelerated industrialization and urbanization. In this paper, land use change dynamics were investigated by the combined use of satellite remote sensing, geographic information systems (GIS), and stochastic modelling technologies. The results indicated that there has been a notable and uneven urban growth and a tremendous loss in cropland between 1989 and 1997. The land use change process has shown no sign of becoming stable. The study demonstrates that the integration of satellite remote sensing and GIS was an effective approach for analyzing the direction, rate, and spatial pattern of land use change. The further integration of these two technologies with Markov modelling was found to be beneficial in describing and analyzing land use change process.


Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis.
Asthma is a complex chronic disease underpinned by pathological changes within the airway wall. How variations in structural airway pathology and cellular inflammation contribute to the expression and severity of asthma are poorly understood. Therefore we evaluated pathological heterogeneity using topological data analysis (TDA) with the aim of visualizing disease clusters and microclusters. A discovery population of 202 adult patients (142 asthmatic patients and 60 healthy subjects) and an external replication population (59 patients with severe asthma) were evaluated. Pathology and gene expression were examined in bronchial biopsy samples. TDA was applied by using pathological variables alone to create pathology-driven visual networks. In the discovery cohort TDA identified 4 groups/networks with multiple microclusters/regions of interest that were masked by group-level statistics. Specifically, TDA group 1 consisted of a high proportion of healthy subjects, with a microcluster representing a topological continuum connecting healthy subjects to patients with mild-to-moderate asthma. Three additional TDA groups with moderate-to-severe asthma (Airway Smooth MuscleHigh, Reticular Basement MembraneHigh, and RemodelingLow groups) were identified and contained numerous microclusters with varying pathological and clinical features. Mutually exclusive TH2 and TH17 tissue gene expression signatures were identified in all pathological groups. Discovery and external replication applied to the severe asthma subgroup identified only highly similar "pathological data shapes" through analyses of persistent homology. We have identified and replicated novel pathological phenotypes of asthma using TDA. Our methodology is applicable to other complex chronic diseases.


Erector spinae plane block versus intercostal nerve block for postoperative analgesia in lung cancer surgery.
A recent trend in postoperative analgesia for lung cancer surgery relies on regional nerve blocks with decreased opioid administration. Our study aims to critically assess the continuous ultrasound-guided erector spinae plane block (ESPB) at our institution and compare it to a standard regional anesthetic technique, the intercostal nerve block (ICNB). A prospective randomized-control study was performed to compare outcomes of patients, scheduled for video-assisted thoracoscopic (VATS) lung cancer resection, allocated to the ESPB or ICNB group. Primary outcomes were total opioid consumption and subjective pain scores at rest and cough each hour in 48 h after surgery. The secondary outcome was respiratory muscle strength, measured by maximal inspiratory and expiratory pressures (MIP/MEP) after 24 h and 48 h. 60 patients met the inclusion criteria, half ESPB. Total opioid consumption in the first 48 h was 21. 64 ± 14.22 mg in the ESPB group and 38.34 ± 29.91 mg in the ICNB group (p = 0.035). The patients in the ESPB group had lower numerical rating scores at rest than in the ICNB group (1.19 ± 0.73 vs. 1.77 ± 1.01, p = 0.039). There were no significant differences in MIP/MEP decrease from baseline after 24 h (MIP p = 0.088, MEP p = 0.182) or 48 h (MIP p = 0.110, MEP p = 0.645), time to chest tube removal or hospital discharge between the two groups. In the first 48 h after surgery, patients with continuous ESPB required fewer opioids and reported less pain than patients with ICNB. There were no differences regarding respiratory muscle strength, postoperative complications, and time to hospital discharge. In addition, continuous ESPB demanded more surveillance than ICNB.


Informatics and Geriatric Psychiatry.
The rapidly growing discipline of medical informatics is changing the face of clinical practice and research. The author reviews current efforts toward the development of electronic medical record systems. A successful system must provide satisfactory solutions to five major requirements: a user interface acceptable to varied health care personnel, data storage and transmission standards that will allow communication with other systems, a coding system that is flexible but accommodates complex queries, a multilevel security structure and audit trail, and unique identifiers for patients and providers. These issues have not been fully resolved, and replacement of paper charts with fully computerized records is many years away, but the application of readily available computer tools to geriatric psychiatry can yield immediate benefits. The author describes a supplemental record system that provides improved organization of clinical information as well as powerful search capabilities.


[Amyotrophic lateral sclerosis also threatens the octogenarian].
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, incurable, mostly declared near the age of sixty-seventy, but more rarely for the older individuals. Because presenting symptoms are non specific (muscle weakness, functional decline, loss of ambulation, dyspnea, dysphagia), diagnosis in early stages may be difficult and delayed, particularly on polymorbid older patients. Symptomatic management is the mainstay of treatment for ALS; care in multidisciplinary team, with maximal psychologic support, is associated with enhanced quality of life. In this article we remind markings aspects of ALS of the older subject, in the light of the follow-up of five patients in our geriatric service.


Cor triatriatum sinister with an intact interatrial septum and a decompressing vein in a toddler.
Cor triatriatum sinister is a very rare cardiac anomaly that may lead to pulmonary hypertension, right ventricular dilation, and eventually right heart failure. We report a case of a toddler who presented with respiratory distress and cardiomegaly and was found to have cor triatriatum sinister with a restrictive communication, decompressing vertical vein, pulmonary hypertension, severe tricuspid regurgitation, and severe right ventricular dysfunction. She underwent a successful surgical repair, with normalisation of right ventricular function and pulmonary artery pressure.


Newton's laws of motion in the form of a Riccati equation.
We discuss two applications of a Riccati equation to Newton's laws of motion. The first one is the motion of a particle under the influence of a power law central potential V(r)=kr(epsilon). For zero total energy we show that the equation of motion can be cast in the Riccati form. We briefly show here an analogy to barotropic Friedmann-Robertson-Lemaitre cosmology where the expansion of the universe can be also shown to obey a Riccati equation. A second application in classical mechanics, where again the Riccati equation appears naturally, are problems involving quadratic friction. We use methods reminiscent to nonrelativistic supersymmetry to generalize and solve such problems.


Leveraging history to improve crisis response.
In the words of George Santayana: 'Those who cannot remember the past are condemned to repeat it'. To navigate the future successfully, an understanding of the past is invaluable. This paper focuses on the stories of past disasters and the lessons they teach us. Such simple yet powerful lessons improve the ability to sell the importance of preparation. The paper focuses on trends discovered while teaching global leaders to prepare for disaster events. It is the stories that convince them to own their business continuity programme. These same stories can help management understand the importance of learning from the past.


Long-Term High Salt Intake Involves Reduced SK Currents and Increased Excitability of PVN Neurons with Projections to the Rostral Ventrolateral Medulla in Rats.
Evidence indicates that high salt (HS) intake activates presympathetic paraventricular nucleus (PVN) neurons, which contributes to sympathoexcitation of salt-sensitive hypertension. The present study determined whether 5 weeks of HS (2% NaCl) intake alters the small conductance Ca2+-activated potassium channel (SK) current in presympathetic PVN neurons and whether this change affects the neuronal excitability. In whole-cell voltage-clamp recordings, HS-treated rats had significantly decreased SK currents compared to rats with normal salt (NS, 0.4% NaCl) intake in PVN neurons. The sensitivity of PVN neuronal excitability in response to current injections was greater in HS group compared to NS controls. The SK channel blocker apamin augmented the neuronal excitability in both groups but had less effect on the sensitivity of the neuronal excitability in HS group compared to NS controls. In the HS group, the interspike interval (ISI) was significantly shorter than that in NS controls. Apamin significantly shortened the ISI in NS controls but had less effect in the HS group. This data suggests that HS intake reduces SK currents, which contributes to increased PVN neuronal excitability at least in part through a decrease in spike frequency adaptation and may be a precursor to the development of salt-sensitive hypertension.


A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling.
Epidermal growth factor (EGF) and type alpha transforming growth factor (TGF-alpha) bind to a specific region in subdomain III of the extracellular portion of the EGF receptor (EGFR). Binding leads to receptor dimerization, auto-and transphosphorylation on intracellular tyrosine residues, and activation of signal transduction pathways. We compared the binding and biological actions of EGF and TGF-alpha in Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or a variant EGFR that has an arginine-to-lysine substitution in the extracellular domain at codon 497 (HER497K) within subdomain IV of EGFR. Both receptors exhibited two orders of binding sites with radioiodinated EGF (125I-EGF). Similar results were obtained with 125I-TGF-alpha in cells expressing HER497R. In contrast, only one order of low-affinity binding sites was seen with 125I-TGF-alpha in the case of HER497K. Although EGF and TGF-alpha enhanced tyrosine phosphorylation of both receptors, CHO cells expressing HER497K exhibited an attenuated growth response to EGF and TGF-alpha and a reduced induction of the protooncogenes FOS, JUN, and MYC. Moreover, high concentrations of TGF-alpha (5 nM) inhibited growth in these cells but not in cells expressing HER497R. These findings indicate that a region in subdomain IV of EGFR regulates signal transduction across the cell membrane and selectively modulates that binding characteristics of TGF-alpha.


Autosomal genome scan for loci linked to blood pressure levels and trends since childhood: the Bogalusa Heart Study.
Genetic loci influencing the long-term levels and trends of blood pressure over time were investigated using 775 white siblings, ages 13 to 43 years, enrolled in the Bogalusa Heart Study, and 357 microsatellite markers on the 22 autosomal chromosomes. Subjects had been examined serially 2 to 12 times with 4365 serial observations over an average of 22 years from childhood to adulthood. Total and incremental area under the curve was calculated based on a cubic growth curve and used as long-term levels and trends, respectively. After adjusting for age, sex, and body mass index, heritability estimates of total area were 0.66 for systolic and 0.68 for diastolic blood pressure. Heritability of incremental area was 0.38 for systolic and 0.46 for diastolic blood pressure. Significant linkage to the total area of diastolic blood pressure (peak logarithm of odds [LOD]=3.9 at 73 cM) was observed on chromosome 2, with a region spanning from 44 cM to 103 cM showing supporting linkage evidence of LOD >3.0. In addition, suggestive linkage for total area of systolic (LOD=1.6 at 182 cM) and diastolic blood pressure (LOD=2.0 at 36 cM) on chromosome 4 and diastolic blood pressure incremental area (LOD=2.2 at 28 cM) on chromosome 18 was noted. Several hypertension candidate genes such as alpha-adducin, beta-adducin, sodium bicarbonate co-transporter, and G protein-coupled receptor kinase 4 are located in these regions. Linkage evidence found in this community-based study indicates that regions on these chromosomes harbor genetic loci that affect the propensity for development of hypertension from childhood.


Glycogen and glycogen enzymes in the liver and striated muscle of rats under altered thyroid states.
Changes induced in liver and striated muscle glycogen and glycogen enzymes (glycogen synthetase, glycogen phosphorylase and alpha-amylase) by hypothyroidism and hyperthyroidism in rats have been determined. There were no changes in liver glycogen synthetase, phosphorylase and amylase activities in the hypothyroid group. Hyperthyroid rats showed lower liver glycogen synthetase, phosphorylase a and amylase activities. In muscle, hypothyroid rats had lower phosphorylase activity. In the hyperthyroid group glycogen synthetase was increased.--The results presented do not completely agree with the glycogen levels found in both tissues studied, and they are obviously more related to other factors such as glucose availability. It can be concluded that under the conditions studied, the glycogen enzyme levels could not alone explain the variations of glycogen levels.


High incidence of genotypic variance between sequential herpes simplex virus type 2 isolates from HIV-1-seropositive patients with recurrent genital herpes.
We developed a polymerase chain reaction (PCR) method, based on strain-to-strain variation of DNA repeats in the herpes simplex virus type 2 (HSV-2) genes US1 and US12, to genotype HSV-2 strains and determine the incidence and risk factors associated with HSV-2 superinfection in patients with recurrent genital herpes (RGH). Forty-seven (92%) of 51 unrelated HSV-2 isolates could be distinguished. Genotyping of sequential HSV-2 isolates showed a different genotype in all of the 11 human immunodeficiency virus type 1 (HIV-1)-seropositive patients with RGH, compared with 1 of the 8 HIV-1-seronegative patients with RGH. The PCR approach developed distinguishes unrelated HSV-2 strains efficiently and indicated a high incidence of genotype variance between sequential HSV-2 isolates of HIV-1-seropositive patients with RGH.


Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca(2+) cycling proteins.
Cardiac hypertrophy is a compensatory stage of the heart in response to stress such as pressure overload (PO), which can develop into heart failure (HF) if left untreated. Resveratrol has been reported to prevent the development of hypertrophy and contractile dysfunction induced by PO. However, other studies found that resveratrol treatment for a longer period of time failed to regress cardiac hypertrophy. The aim of this study is to determine the timing of resveratrol treatment to achieve antihypertrophic effect and investigate whether resveratrol prevents the development of HF through preservation of myocardium structure and modulation of Ca(2+) handling proteins. To generate rats with cardiac hypertrophy, male Sprague-Dawley rats were subjected to PO (aortic banding procedure) for 4 weeks. Sham-operated animals served as controls. Rats with cardiac hypertrophy were given resveratrol (4 mg/kg/day) for 4, 6, and 8 weeks, respectively. Histological and echocardiographic analysis and transmission electron microscopy were performed to assess cardiac structure and function. The levels of Ca(2+) handling proteins were measured by western blot analysis. Histological analysis showed that resveratrol treatment regressed developed cardiac hypertrophy at 8 and 10 weeks postsurgery, but not at 12 weeks. However, resveratrol strongly and continuously prevented the development of cardiac dysfunction and dilation of cardiac chamber as evaluated by echocardiography and H&E staining of heart cross-sections. In addition, PO-induced cardiac fibrosis was completely inhibited by resveratrol treatment. Resveratrol markedly prevented the disrupted myocardium but partially rescued mitochondrial abnormality in banded rats. Moreover, resveratrol prevented the alteration of Ca(2+) handling proteins induced by aortic banding, including downregulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and ryanodine receptor 2 (RyR2), hypophosphorylated phospholamban (PLB), upregulation of Na(+)/Ca(2+)-exchangers (NCX1) and increased expression and phosphorylation of Ca(2+)/calmodulin -dependent protein kinase II (CaMKII). Moreover, resveratrol alleviated the decreased SERCA activity induced by aortic banding. Resveratrol effectively prevented the transition from compensatory to decompensatory stage of cardiac hypertrophy induced by PO, but this effect is dependent on the timing of treatment. We suggest that resveratrol may exert beneficial effects on cardiac hypertrophy through protection of cardiac structure and modulation of Ca(2+) handling proteins.


Outbreak of influenza and rhinovirus co-circulation among unvaccinated recruits, U.S. Coast Guard Training Center Cape May, NJ, 24 July-21 August 2016.
Military and Coast Guard recruits are particularly susceptible to respiratory infections. Although seasonal influenza vaccinations are mandatory for recruits, the vaccine expires annually in June. On 29 July 2016, the U.S. Coast Guard Training Center Cape May, NJ, identified an increase in febrile respiratory illness (FRI) among recruits. During 24 July-21 August, a total of 115 recruits reported symptoms. A total of 74 recruits tested positive for respiratory infections: influenza A (H3) (n=34), rhinovirus (n=28), influenza/rhinovirus co-infection (n=11), and adenovirus/rhinovirus co-infection (n=1), while 41 recruits had no laboratory-confirmed specimen but were considered suspected cases. Only one recruit reported receiving the seasonal influenza vaccine within the previous 12 months. Influenza predominated during 24 July-6 August, whereas rhinovirus predominated during 7 August-20 August. Most (92.2%) cases were identified in four of 10 recruit companies; incidence rates were highest among recruits in weeks 2-4 of an 8-week training cycle. Key factors for outbreak control included rapid detection through routine FRI surveillance, quick decision-making and streamlined response by using a single chain of command, and employing both nonpharmaceutical and pharmaceutical interventions.


Quantified Facial Rejuvenation Utilizing High Intense Focus Ultrasound with Multiple Penetrative Depths.
Multiple penetration depths of high-intensity focused ultrasound (HIFU) treatment for facial rejuvenation have not been quantified. We enrolled 12 participants (n=24) to undergo one session of HIFU rejuvenation between January 1, 2019, and January 10, 2020. We used a 2-, 4.5-, and 6-mm focal depth transducer on the upper and middle face. We evaluated efficacy on days 60 and 90 by using our specific assessment system. The average eyebrow peak and pupil-eyebrow peak angles significantly increased by 2° (p < 0.0005) and decreased by 1° (p < 0.0001), respectively, at day 90. The shortened eyebrow-iris length indicated that the forehead tissues had lifted and moved medially to the central face. Supraorbital tissues were also vertically elevated, marked by the eyebrow-orbital (p = 0.0016) and vertical palpebral fissure lengths (p = 0.0052), which both exhibited a 0.8-cm elevation. For the midface, the increased canthus-oral-nasal angle (p = 0.5881) and decreased tragus-oral length (p = 0.5881) indicated that laxity had been corrected through lifted oral commissure, though the data were not statistically significant. No serious side effects were observed. HIFU treatment with multiple depths quantitatively improved both upper-facial rejuvenation and midface rejuvenation after a single session.


[Thyroid surgery: generalist or specialist?].
Thyroid surgery is done in Germany in a considerable numbers of operations (about 110,000 per year). To perform thyroid operations by so called "generalists" or "specialists" have been discussed intensively, however, this issue have not been analyzed in detail. Study material comprised 16,500 consecutive thyroid operations with 30,000 operated sites that have been prospectively documented in the German Thyroid Multicenter Study performed 1998 through 2001. Quality of surgery were analyzed by calculating the inverse relationship between volume and outcome (complication rate). To achieve complication rates (permanent unilateral recurrent laryngeal nerve paralysis and hypocalcemia) of < 1 % (primary surgery) or < 3 % (redo surgery) the minimum number of thyroid operations of lower level of experience (e. g. benign nodular goiter) per year was n=30. The minimum number of operations with higher level of experience was significantly lower (n=3-12) due to the higher level of experience of operating surgeons. In contrast to the rates of postoperative hypocalcemia the rates of postoperative recurrent laryngeal nerve paralysis was clearly related to the number of thyroid operations performed. The high number of thyroid operations in Germany with about 20 % of operations of high level experience are requiring surgical curricula and hospital structures that offer as well generalists as specialists to treat the broad spectrum of thyroid diseases accordingly. To lower the complication rate especially of difficult thyroid operations the level of specialization in Germany have to be increased.


P059 Impact of PHQ-9 Screen on Early Identification of Depression in IBD Clinic.
Over the past two decades there has been significant research linking inflammatory bowel disease (IBD) to depression. The chronicity of symptoms coupled with the financial burden of treatment costs, missed days of work/school and interpersonal relationship stress are contributing factors in the diagnosis of depression. The prevalence of depression within the IBD community is 15% and depressive symptoms are noted in 20% of patients. Furthermore, IBD patients with severe uncontrolled disease have higher rates of depression (40.7%) than those in remission (16.5%). The association between IBD and depression is linked to lower quality of life, poor medication compliance, worse disease outcomes, increased hospitalization, and higher suicidal risk. Early diagnosis and treatment of depression in IBD patients is paramount in achieving and maintaining IBD disease remission. While the association between IBD and depression is well-known, identifying depression can be a challenge. Review of recent literature shows that depression is under screened in IBD clinics. We present a prospective quality improvement study at a robust IBD center evaluating the impact of a validated depression screen (PHQ-9) on identifying depression compared to standard of care. We compared the prevalence of depression in the IBD clinic in the control group using the history and diagnosis of depression and compared it against the intervention group after HQ-9 screening. Control group patient data was collected from June 2020 to July 2020 via virtual and in person visits. Intervention group PHQ-9 data was collected in person visits from January - March 2020 and post-intervention data collection was placed on hold until November 2020 due to the COVID pandemic. One randomly selected patient from each clinic session was asked to participate in the study at the time of visit. The primary end point was to compare the rates of depression and identify any barriers in providing early treatment for depression. The secondary endpoint was to identify high risk patients that are prone to depression. Categorical variables were analyzed by chi square analysis or fischer exact tests. Numerical data were analyzed using T-test. A total of 111 patients were screened. 60 patients were randomized to the control group (i.e. EMR based review for depression) and 51 patients were screened via survey during in person clinic visit. The identified depression rate from control vs intervention group is 20% vs. 35% (p = 0.071). Rates of depression were 15% in non-fistulizing Crohn's disease vs. 41.4% in fistulizing Crohn's disease (p = 0.003). Multivariate model for predicting depression noted to be significant for extra-intestinal manifestations OR of 3.06 (1.03, 9.12) p = 0.045 and age OR of 0.97 (0.94, 1.00) p = 0.042. Control vs. intervention identification of depression in patients with extra-intestinal manifestations is notable for OR of 3.31 (1.15, 9.52) p = 0.026 in the univariate model and OR of 3.30 (1.07, 10.16) p = 0.038 in the multivariate model. Key findings including identification of depression is higher in the intervention group compared to the control group. Though the data is not statistically significant, this is likely secondary to the small sample size in the setting of the pandemic. In addition, univariate analysis revealed a statistically significant finding that the older the age of the patient, the less likely they are to have depression. Our data showed that the mean age of depressed patients was 38.3 compared to nondepressed patients whose mean age is 47.1. Further analysis can help elucidate this finding, for example identifying if older patients are being treated for depression or more likely to seek out therapists compared to younger patients. Univariate analysis also revealed that intestinal Crohn's disease was a risk factor for depression. This is possibly secondary to the severity of disease in these individuals, especially if their IBD is causing an impact on their quality of life. Looking into the number of hospitalizations, days off from work or school, and coexisting medical diagnoses can allow us to further understand if depression stems from their disease. Given preliminary findings, we plan to continue this study for a larger sample size and further determine if there is a significant delay in identifying depression with the current standard of care.


[Substance P--results of observing the course of plasma levels during heart surgery].
Observing substance P plasma level changes, we examined the adaptation capacities of the human organism in hypothermia during cardiosurgical operations. It was our aim to observe stress-induced changes of substance P concentrations and to find ways of using them as indicators of good or bad adaptation capacity. Plasma level controls were made on 40 cardiosurgical patients. In all cases the substance P concentration varied in correlation to operation-induced periods of stress. There was a clear tendency for all patients to react similarly, although some individual deviations were found, too. Obviously stress provokes a consumption of substance P in plasma which is expressed in decreasing concentrations. Its rapid increase, however, indicates a good adaptation capacity. Since the need for an exogenous substance P substitution was not recognizable at the beginning of the operation, at present only the possibility of prophylactic substitution is given.


Listening levels through hearing aids: a difference of opinion.
The present authors find it impossible to compare their work with that of Powell & Tucker (Scand Audiol 5, 167, 1976) due to the lack of original data in the latter paper. The present authors papers were not written with the prime view of presenting predictive values but of reporting data on hearing aid users. The predictive value of our results has been largely and not very carefully inferred by Powell & Tucker. The predictive values of gain or output may be inferred from current research and the Powell & Tucker paper confirms the previous work rather than repudiates it. It is obvious that research workers should co-operate in using clearly stated methods and publishing original data in their papers. Furthermore it is important that the terminology used is of a standard form--or if not, that each new term is clearly defined.


[Early detection of cervical cancer in Chile: time for change].
Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.


[Exposure to air pollutants in the city of Bari].
Air pollution leads to increased levels of morbidity and mortality for cardiovascular and respiratory diseases in populations living in urban environments. Our study tested the possibility of using sampling techniques that are typical of industrial hygiene to measure exposure to atmospheric pollutants and using personal samplers for concentrations of certain pollutants to which an ordinary resident of Bari is exposed on a daily basis. We monitored dusts (PM10, PM2.5), CO, CO2, humidity, ventilation and noise, by dynamical sampling along a route on foot, bicycle, motorbike and automobile and then compared the results with data provided by fixed stations distributed in the municipality of Bari. By comparing our data with those values provided for by the law, we found out that the concentrations of all pollutants resulted to be higher than 50 microg/m3, with the exception of the measurements carried out along the route by car. The measurements of PM2.5 were, on average, similar to the values of PM10 for the route on foot, but they were totally different for the measurements made along the route by car, bicycle and motorbike. Moreover, comparing our data with those obtained from the municipal network of fixed stations, we found that results provided by our measurements were higher for PM10. Considering that compliance with the limits set by law refers to average values over 24 hours, we can conclude that those hours in which pollutant concentration reaches a risk level shall be considered especially regarding groups of people with respiratory disorders.


Catalytic Depolymerization of Alkali Lignin Using Supported Pt Nanoparticle Catalysts.
Alkali lignin, a byproduct of the pulping process, was depolymerized using Pt nanoparticle catalysts. A depolymerized lignin with a lower molecular weight was obtained and characterized with GPC and NMR. 31P-NMR using OH-sensitive probing molecules showed the formation of guaiacyl OHs during the reaction, indicating the cleavage of guaiacyl ether bonds.


Detecting and quantifying the adventitious presence of transgenic seeds in safflower, Carthamus tinctorius L.
Safflower ( Carthamus tinctorius L.) is currently being developed as a platform for the production of novel proteins. Methods for detecting and quantifying transgenic safflower are needed to ensure seed quality and to monitor for its adventitious presence. We developed and compared three methods of assaying for transgenic safflower presence in conventional seedlots: field bioassays, enzyme-linked immunosorbent assays (ELISA), and quantitative polymerase chain reaction (Q-PCR). Limits for reliable quantification for both ELISA and Q-PCR are approximately 0.1%, although levels at least as low as 0.02% can be detected by Q-PCR. Levels of quantification for the field bioassay are limited only by space and resources available. Multiple sampling methods to detect and quantify transgenic safflower presence at levels lower than 0.1% were used on field collected samples from a pollen outcrossing experiment to quantify the adventitious presence of transgenic safflower. Taking into account the potential utility and relative advantages or disadvantages of each detection method, it is recommended that the initial testing for the adventitious presence of transgenic seed be carried out using an antibody-based test if available and that Q-PCR-based assays to quantify transgenic proportion be used when it is necessary to identify specific transgenic constructs or if antibody-based assays are not readily available.


Greater Food-Related Stroop Interference Following Behavioral Weight Loss Intervention.
Individuals who have successfully lost and maintained weight have slower reaction times on food-related Stroop tasks, indicating greater cognitive interference to food stimuli compared to obese and normal weight individuals. It remains unclear whether this interference is a preexisting characteristic of weight loss maintainers or if food-interference changes in obese individuals as they lose weight. To examine potential changes in food-related interference, a food-Stroop paradigm was used to measure responses to food versus non-food words in 13 obese women before and after a 12-week behavioral weight loss program. Participants achieved a mean weight loss of 5.12 kg through the behavioral weight loss program. Their reaction time to food words became significantly slower (p<0.001) and they made significantly more errors (p<0.01) following treatment. These findings suggest that through behavioral weight loss treatment obese individuals experience increased interference toward food words, which may reflect increased salience of food-related cues. Future research is needed to determine whether increases in interference are related to better weight loss and maintenance.


[Preparation and characterization of bovine bone collagen matrix].
A process of preparing bovine cortical bone in order to form materials suitable for biomedical xenograft implants was described. Fresh bone samples cut from the middiaphyseal region of bovine femora were obtained from a local slaughterhouse. The bovine bone collagen matrix (BBCM) of various shapes fabricated from bovine bone by defatting and deproteination procedure may be implanted surgically for various purposes. The bone cubes were first defatted in a mixture of defatting agent; subsequently, the samples were extracted to release noncollagenous proteins, followed by digestion using a proteolytic enzyme to remove the telopeptide portions of collagen and residual noncollagenous proteins. Finally,the samples were dried in vacuum, packed and sterilized by gamma irradiation. The bone specimens were characterized by a suite of analytical techniques involving FTIR spectroscopy, X-ray diffraction spectroscopy, differential scanning calorimetry (DSC), uniaxial tension mechanical tests and scanning electron microscopy (SEM). The result showed that BBCM occurred as a white structure with suitable porosity. It contains reasonable proprotion of mineral and organic components in the original osseous architecture of the bovine bone, which is beneficial to keeping the mechanic property and weaker immunogenicity; therefore, it can serve as a potential bone implantable material and extracellular matrix material in bone tissue engineering.