The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.
Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. We analyzed - 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 9.0331, p = 0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ2 = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV1% and FEV1/FVC) and protein level was found. We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.


Immunoscintigraphy of ovarian carcinoma using a monoclonal antibody (111In-NCRC48) defining a polymorphic epithelial mucin (PEM) epitope.
An anti-polymorphic epithelial mucin (PEM) monoclonal antibody NCRC48 (IgG3) has been tested for its capacity to localize in tumours according to accepted guidelines for human administration. Following radiolabelling with 111In, 1 mg antibody was administered to 19 patients with a clinical suspicion of ovarian malignancy. Initial imaging and biodistribution studies confirm the safety of this conjugate although six out of 11 patients tested developed an antibody response to the monoclonal antibody. Immunoscintigraphy with this antibody was compared with magnetic resonance imaging and ultrasound in relation to the final tumour histology, the final accuracies being 79, 79 and 64% respectively. Positive localization of antibody was confirmed in malignant tissue with little evidence of uptake in benign tissue.


Poliovirus can enter and infect mammalian cells by way of an intercellular adhesion molecule 1 pathway.
Mouse fibroblast cell lines were transfected with truncated forms of the human poliovirus receptor (PVR) cDNA and tested for the expression of functional receptors for poliovirus. Several receptor constructs, all containing the coding region of the first 143 amino acids of PVR, were able to render mouse cells susceptible to poliovirus infection. A deletion of 65 amino acids in the first extracellular domain of PVR prevented virus attachment and infection. These data suggest that domain 1 is necessary and sufficient for the virus-receptor interaction. A PVR/intercellular adhesion molecule 1 hybrid receptor, expressing the PVR variable domain on a truncated receptor molecule for human rhinovirus 14, was shown to be a functional receptor for poliovirus. This observation indicates that, subsequent to attachment to the PVR-binding domain, poliovirus can use the same pathway as the major receptor group rhinoviruses to enter cells.


Comparison of three transgenic Bt rice lines for insecticidal protein expression and resistance against a target pest, Chilo suppressalis (Lepidoptera: Crambidae).
Two transgenic rice lines (T2A-1 and T1C-19b) expressing cry2A and cry1C genes, respectively, were developed in China, targeting lepidopteran pests including Chilo suppressalis (Walker) (Lepidoptera: Crambidae). The seasonal expression of Cry proteins in different tissues of the rice lines and their resistance to C. suppressalis were assessed in comparison to a Bt rice line expressing a cry1Ab/Ac fusion gene, Huahui 1, which has been granted a biosafety certificate. In general, levels of Cry proteins were T2A-1 > Huahui 1 > T1C-19b among rice lines, and leaf > stem > root among rice tissues. The expression patterns of Cry protein in the rice line plants were similar: higher level at early stages than at later stages with an exception that high Cry1C level in T1C-19b stems at the maturing stage. The bioassay results revealed that the three transgenic rice lines exhibited significantly high resistance against C. suppressalis larvae throughout the rice growing season. According to Cry protein levels in rice tissues, the raw and corrected mortalities of C. suppressalis caused by each Bt rice line were the highest in the seedling and declined through the jointing stage with an exception for T1C-19b providing an excellent performance at the maturing stage. By comparison, T1C-19b exhibited more stable and greater resistance to C. suppressalis larvae than T2A-1, being close to Huahui 1. The results suggest cry1C is an ideal Bt gene for plant transformation for lepidopteran pest control, and T1C-19b is a promising Bt rice line for commercial use for tolerating lepidopteran rice pests.


On the roles of extracellular matrix remodeling by gelatinase B.
Human extracellular matrix is constantly remodelled by de novo synthesis of structural components and by degradation of the matrix proteins by various proteinases. The secreted proteolytic enzymes are regulated at several levels: by control of gene transcription, by glycosylation, by specific inhibitors and by enzyme activation processes. The latter level most often involves clipping of a proenzyme or zymogen into an active proteinase. A series of such activation reactions leads to enzyme cascades. Whereas proteolytic activation is an all-or-none phenomenon, glycosylation usually has a restricted or fine-tuning effect on the catalytic activity of enzymes. Commonly, a two- to threefold reduction in specific activity is imposed by N-glycosylation on each member of the multi-enzyme chain. In a series comprising e.g. four enzymes, this can lead to significant influences (2(4)-3(4)-fold increase) on the substrate converting activity of the terminal member of a cascade. Gelatinase B is a terminal member of the protease cascade which leads to matrix degradation. It cleaves gelatins (denatured collagens or collagen fragments after digestion by collagenase) and other substrates and is thought to be involved in matrix remodeling during the normal processes of embryogenesis, tissue remodeling and development. Gelatinase B expression is upregulated in pathological states such as invasion of cancer cells and when leukocytes are released from the bone marrow and migrate towards an inflammatory focus. Proteases, including gelatinase B, are transcriptionally regulated by cytokines and directly by the activation processes. The gene regulation of enzyme inhibitors as well as other humoral factors, which contribute to protease activation, influence protease activities in an indirect way. Proteases might also play a role in the pathophysiology of chronic inflammation and autoimmunity by cleaving extracellular structural proteins and by generating proteolytic fragments. Indeed, these remnant fragments antigenically resemble the original precursor proteins, but are structurally and quantitatively different and may provoke an autoimmune response. Application of the knowledge of the structure, function and regulation of gelatinase B has contributed to the understanding of the mechanism of action of some gelatinase-inhibiting antirheumatic drugs and promises to contribute further to the development of novel treatment strategies for autoimmune diseases such as multiple sclerosis and for invasive cancers.


Administration of BNT162b2 mRNA COVID-19 vaccine to subjects with various allergic backgrounds.
The mRNA-based COVID-19 vaccine was introduced to the general public in December 2020. Shortly thereafter, safety concerns were raised due to the reporting of allergic reactions. Allergy-related disorders were suspected to be significant risk factors and the excipient polyethylene glycol was suggested to be a robust allergen. This is a retrospective study analysis. Subjects with putative risk factors for severe allergic reactions to the Pfizer-BioNTech BNT162b2 vaccine were referred for vaccination under observation at the Unit of Allergy and Clinical Immunology. Data was collected for each subject, including demographic details, medical history and previous reactions to any allergen. When appropriate, skin tests were done prior to vaccination. A total of 346 subjects received 623 vaccine doses under observation. The study included patients with various allergy-related disorders (n=290) and those with allergy to a previous COVID-19 vaccine dose (n=56). Both groups showed female predominance (78% and 88%, p=NS). Patients without reactions to previous doses reported more drug allergy (80% vs. 39%, p<0.001) and previous anaphylaxis (64% vs. 14%, p<0.001). There was no difference in sensitivity to other allergens, including polyethylene glycol. Under observation, mild allergic reactions were noted in 13 individuals characterized by female gender (100%), a history of anaphylaxis (69%) and drug allergy (62%). In 7 subjects, allergy was treated with antihistamines while others recovered spontaneously. Our study demonstrates that vaccination under specialist-supervision is a powerful tool for reducing over-diagnosis of systemic reactions and for rapid and reliable collection of vaccine safety data.


Development of Redox Metabolic Imaging Using Endogenous Molecules.
Redox metabolism plays a central role in maintaining homeostasis in living organisms. The electron transfer system in mitochondria produces ATP via endogenous redox molecules such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and coenzyme Q10 (CoQ10), which have flavin or quinone moieties. One-electron transfer reactions convert FMN, FAD, and CoQ10 to the free radical intermediates FMNH and FADH, and CoQ10H, respectively. Dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) allows us to visualize free radicals in vitro and in vivo. We present a spectroscopic imaging technology with DNP-MRI, which enables the imaging of multiple free radical intermediates such as FADH and CoQH. DNP-MRI can also identify various endogenous free radical intermediates derived from redox transformations.


Malignant progression in choroid plexus papillomas.
Malignant progression of choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed. Frequency and extent of malignant progression were examined in a retrospective series of 124 primary choroid plexus papillomas using uniform histological criteria. After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neurosurgical intervention had occurred in the 103 cases of choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical choroid plexus papilloma than in cases of choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examination as well as Ki 67 (MIB-1) proliferation indices (median value 4% for both primary and recurrent tumors; range 0-15% for primary compared with 0-12% for recurrent tumors). However, two patients experienced a transition from a choroid plexus papilloma (WHO Grade I) and an atypical choroid plexus papilloma (WHO Grade II) to choroid plexus carcinomas (WHO Grade III). Recurrent tumor growth after gross-total resection is rare in choroid plexus papillomas, but malignant progression to choroid plexus carcinoma does occur in a small percentage of tumors.


Cell envelope morphology of rumen bacteria.
The cell walls of three species of rumen bacteria (Bacteroides ruminicola, Bacteroides succinogenes, and Megasphaera elsdenii) were studied by a variety of morphological methods. Although all the cells studied were gram-negative and had typical cytoplasmic membranes and outer membranes, great variation was observed in the thickness of their peptidoglycan layers. Megasphaera elsdenii evidenced a phenomenally thick peptidoglycan layer whose participation in septum formation was very clearly seen. All species studied have cell wall "coats" external to the outer membrane. The coat of Bacteroides ruminicola is composed of large (approximately 20 nm) globules that resemble the protein coats of other organisms, whereas the coat of Bacteroides succinogenes is a thin and irregular carbohydrate coat structure. Megasphaera elsdenii displays a very thick fibrillar carbohydrate coat that varies in thickness with the age of the cells. Because of the universality of extracellular coats among rumen bacteria we conclude that the production of these structures is a protective adaptation to life in this particular, highly competitive, environment.


Toward refinement in rhinoplasty.
Three interrelated principles can help to achieve nasal refinement: creation of nasal planes, attention to lateral light reflexes, and maintenance of skin sleeve size. These principles are detailed and illustrated in primary and secondary rhinoplasty patients.


The Relationship Between Suicidal Behaviors and Zero Suicide Organizational Best Practices in Outpatient Mental Health Clinics.
This study tested the hypothesis that fidelity of clinics to Zero Suicide (ZS) organizational practices is inversely related to suicidal behaviors of patients under clinical care. Using cross-sectional analyses, the authors examined the fidelity of 110 outpatient mental health clinics to ZS organizational best practices and suicidal behaviors of clinic patients in the year before a large-scale Zero Suicide implementation. Fidelity to ZS organizational best practices was assessed over a 1-year period with an adapted version of the ZS Organizational Self-Study instrument (17 items self-rated on a Likert scale of 1-5). Suicidal behaviors of patients were identified by extracting information on suicide attempts and deaths from a mandated statewide incident-reporting system database. Clinics were dichotomized into any or no suicide incidents during the year of observation. Logistic regression analyses were used to adjust for clinic census and population type (majority child or adult). The clinics (N=110) served 30,257 patients per week. Clinics' total average fidelity score was 3.1±0.6 (range=1.41-4.12). For each point increase in fidelity, clinics had a significantly reduced likelihood of having a suicide incident (adjusted odds ratio=0.31, 95% confidence interval=0.14-0.69). Exploratory analysis identified significant differences for seven of 17 ZS organizational practices, with the largest effect sizes for suicide-specific quality improvement policies and activities (η2=0.097) and lethal means reduction (η2=0.073). These findings support an association between clinics' use of ZS organizational best practices and lower suicidal behaviors of patients under their care. Findings also support the validity of the ZS Organizational Self-Study instrument.


Effectiveness of Duloxetine Monotherapy Compared to Combination Therapy with Other Antidepressants in Patients with Major Depressive Disorder: A Short-Term, Retrospective Study.
The purpose of this study was to compare duloxetine monotherapy to combination therapy with other antidepressants in patients with major depressive disorder in a clinical, real world setting. An eight-week, retrospective, multi-center study of outpatients with major depressive disorder was undertaken. After screening 415 patients, enrolled in this study from July 2009 to June 2014 were 82 patients from among three centers who had been taking duloxetine with or without other antidepressant and not administered with atypical antipsychotics. We compared the mean changes of the Clinical Global Impression-Severity Scale (CGI-S) as a primary measure and the discontinuation rate as a secondary measure between the duloxetine monotherapy group (n=36, 43.9%) and the combination therapy with other antidepressants group (n=46, 56.1%) at baseline, one, two, four and eight weeks. There were no significant differences across the demographic characteristics between two groups. There was, however, a statistically greater improvement on the CGI-S at weeks 2, 4 and 8 in the combination group compared with the monotherapy group. There were no significant differences in discontinuation rate and adverse events between two groups. No serious adverse events were reported in both groups during the study period. This result suggests that the duloxetine combination therapy with other antidepressants could improve effectiveness and have comparable tolerability with the monotherapy in the treatment of outpatients with major depressive disorders in a naturalistic setting. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings.


Approaches in modulating proline metabolism in plants for salt and drought stress tolerance: Phytohormones, mineral nutrients and transgenics.
Major abiotic stress factors such as salt and drought adversely affect important physiological processes and biochemical mechanisms and cause severe loss in crop productivity worldwide. Plants develop various strategies to stand healthy against these stress factors. The accumulation of proline (Pro) is one of the striking metabolic responses of plants to salt and drought stress. Pro biosynthesis and signalling contribute to the redox balance of cell under normal and stressful conditions. However, literature is meager on the sustainable strategies potentially fit for modulating Pro biosynthesis and production in stressed plants. Considering the recent literature, this paper in its first part overviews Pro biosynthesis and transport in plants and also briefly highlights the significance of Pro in plant responses to salt and drought stress. Secondly, this paper discusses mechanisms underlying the regulation of Pro metabolism in salt and drought-exposed plant via phytohormones, mineral nutrients and transgenic approaches. The outcome of the studies may give new opportunities in modulating Pro metabolism for improving plant tolerance to salt and drought stress and benefit sustainable agriculture.


Facial reconstruction using porous high-density polyethylene (medpor): long-term results.
Medpor is a biocompatible, porous, high-density polyethylene implant material used as a skeleton substitute. During the last two decades, it has been successfully applied for aesthetic contour enhancement and at reconstruction of the facial skeleton. Reports on the long-term host tissue tolerance of Medpor are sparse. Use of foreign materials in nasal reconstruction has always been and still is controversial. The main contra-argument maintains that it is not known how alloplastic materials are tolerated by the human body in the long term. This study brings such data concerning the biocompatibility of Medpor. The author has 16 years of experience working with Medpor implants, including its use in rhinoplasty, chin augmentation, and malar augmentation. In this prospective study from 1996 to 2012, Medpor was used in 118 implants for 102 patients. The most frequent indications were nose deformity (n=61), chin hypoplasia (n=33), and malar hypoplasia (n=6). The follow-up periods ranged from 6 months to 15 years (median, 7 years). Of 42 difficult nasal reconstructions performed with the assistance of Medpor, 28 were catastrophe noses that had undergone two to four previous surgeries elsewhere. A total of 19 patients had saddle nose deformity. Of the nasal reconstructions, 85 % had a smooth clinical course, with results remaining stable during the observation time. Five biopsies confirmed soft tissue ingrowths and collagen deposition, with subsequent vascularization. All complications could be mastered. Two dorsal struts and two chin implants required trimming. Infection occurred in three rhinoplasty cases, and partial extrusion occurred in two cases. All augmented chins and malar prominences were firm and bony-like at palpation. Of the 106 Medpor implants in the followed-up patients, some were trimmed or removed, but 97 implants (91%) remained unchanged. Implantation of porous polyethylene in the facial region is a safe procedure. Currently, Medpor seems to be the best alloplastic material available as a facial bone substitute. It is long-lasting, with a low frequency of complications, morbidity similar to procedures involving autologous grafts, and high overall patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Detection of cancer by tumor markers in the blood: a view to the future.
Markers for cancers in the blood include secreted glycoproteins of solid tissue tumors as well as cell surface markers, and chromosomal rearrangements or mutated genes in circulating blood cells. The most successful markers for the diagnosis of solid tissue cancers have been alphafetoprotein and prostate specific antigen. Other markers, such as CEA and a number of carbohydrate epitopes, e.g., CA 15.3, CA 19.9, CA 50, CA 242, and mucin epitopes, such as MCA, CA 125, and DU-PAN-2 are now being used to determine prognosis and to monitor the response to therapy of a variety of cancers. Cytologic markers in the blood include clusters of differentiation (CD) epitopes on blood cells and chromosomal changes, primarily translocations found in many human lymphomas. In the future more specific mutations in specific oncogenes or alterations in expression of oncogenes or suppressor genes, such as p53, may provide clinically useful markers.


Native Hawaiian physician location and service to the underserved in Hawai'i.
This study examined the influence of demographic characteristics, training location, and "practice values" on geographic practice location and serving a medically underserved area/population (MUAP) among physicians of Native Hawaiian ancestry practicing within the State of Hawai'i. A survey assessing factors influencing practice location was mailed to 104 identified Native Hawaiian physicians in the State of Hawai'i with a response rate of 79% (n = 82). Factor analysis was used to identify underlying "practice value" variables important in physician practice location, resulting in three robust factors: (1) professional opportunity, (2) lifestyle, and (3) service. Data were analyzed using chi square, analyses of variance, and logistic regressions. Seventy-eight percent of the Native Hawaiian physicians sampled specialized in primary care, which is significantly more than in the general physician population in Hawai'i (57.3%) and in the continental United States (33.1%). Despite not being located in a MUAP, over half of the physicians felt that they provided important services to their medically underserved patients. Logistic regression models predicted 42% of the variance in practice location and 52% of the variance in serving a MUAP. In general, professional opportunity may be more important for non-MUAP physicians whereas service value may be more essential for MUAP physicians. Additional implications and further research are discussed.


The epidemiology and management of status epilepticus.
Status epilepticus refers to a prolonged seizure state, usually taken as lasting 30 min or longer. This review considers recent studies of the epidemiology of status epilepticus; these have confirmed the high incidence and the high associated mortality and morbidity. Advances in the management of status epilepticus are also reviewed but despite these advances there is still a lack of good comparative studies on which to base treatment regimens.


Evaluating traumatic event scoring schemas for their predictive value to concurrent diagnostic profiles: Texas Childhood Trauma Research Network.
To prospectively chart pathways of risk and resiliency following childhood trauma studies need to address three limitations of prior work: 1) recruit beyond social service/ treatment settings; 2) include broad spectrum of trauma types and 3) cast a broad longitudinal measurement framework of both clinical diagnoses and traumatic exposures. The Texas-Childhood Trauma Research Network (TX-CTRN) is a multi-site collaboration that addresses these limitations. In this baseline-only report, we examined domains of trauma and evaluated the concurrent predictive validity of various traumatic event scoring schemas for clinical diagnoses. Broad-base recruitment of 8-20 year-olds (N = 1289) included trauma centers, emergency departments, pediatric and primary care clinics, and other community settings. Assessments were comprehensive and based on clinical interviews by trained research interviewers. Factor analyses supported a five-factor solution of trauma domains including unintentional/acute, intentional/interpersonal, bullying, in-home versus community witnessed interpersonal harms. Trauma burden scoring schemas were examined for their predictive superiority. Domain-specific counts of traumas that met DSM-5 post-traumatic-stress disorder (PTSD) Criterion-A was the best overall schema in distinguishing among youth with no diagnosis, comorbidities, those with depression, suicidality, substance misuse, and PTSD. There were no assessments of neglect. Findings largely aligned with earlier studies on the relative importance of intentional interpersonal traumas and showed bullying may be an important source of traumatic stress that independently adds to prediction of several diagnoses and should be considered in clinical practice.


Effect of angular momentum on equilibrium properties of a self-gravitating system.
The microcanonical properties of a two-dimensional system of N classical particles interacting via a smoothed Newtonian potential, as a function of the total energy E and the total angular momentum L, are discussed. The two first moments of the distribution of the linear momentum of a given particle at a fixed position show that (a) on average the system rotates like a solid body and (b) the velocity dispersion is a function of the distance from the center. In order to estimate suitable observables, a numerical method based on an importance sampling algorithm is presented. The entropy surface S shows a negative specific heat capacity region at fixed L for all L. Observables probing the average mass distribution are used to understand the link between thermostatistical properties and the spatial distribution of particles. In order to define a phase in a nonextensive system, we introduce a more general observable than that proposed by Gross and Votyakov [Eur. Phys. J. B 15, 115 (2000)]. This observable is the sign of the largest eigenvalue of the Hessian matrix of the entropy surface. If it is negative then the system is in a pure (single) phase; if it is positive then the system undergoes a first order phase transition. At large E the gravitational system is in a homogeneous gas phase. At low E there are several collapse phases. At L=0 there is a single-cluster phase and for L not equal 0 there are several phases with two clusters. The relative size of the clusters depends on L. All these pure phases are separated by a first order phase transition region. Signals of critical behavior emerge at several points of the parameter space (E,L). We also show that a huge loss of information appears if we treat the system as a function of the intensive parameters. Besides the known nonequivalence at first order phase transitions, the pure phases with two clusters of different sizes are not accessible to the canonical ensemble. Moreover, for a particular choice of intensive parameters introduced in this paper, there exist in the microcanonical ensemble some values of those intensive parameters for which the corresponding canonical ensemble does not exist, i.e., the partition sum diverges.


Cloning and expression analysis of carboxyltransferase of acetyl-coA carboxylase from Jatropha curcas.
A full-length cDNA of the carboxyltransferase (accA) gene of acetyl-coenzym A (acetyl-CoA) carboxylase from Jatropha curcas was cloned and sequenced. The gene with an open reading frame (ORF) of 1149 bp encodes a polypeptide of 383 amino acids, with a molecular mass of 41.9 kDa. Utilizing fluorogenic real-time polymerase chain reaction (RT-PCR), the expression levels of the accA gene in leaves and fruits at early, middle and late stages under pH 7.0/8.0 and light/darkness stress were investigated. The expression levels of the accA gene in leaves at early, middle and late stages increased significantly under pH 8.0 stress compared to pH 7.0. Similarly, the expression levels in fruits showed a significant increase under darkness condition compared to the control. Under light stress, the expression levels in the fruits at early, middle and late stages showed the largest fluctuations compared to those of the control. These findings suggested that the expression levels of the accA gene are closely related to the growth conditions and developmental stages in the leaves and fruits of Jatropha curcas.


Mitochondrial complex I inhibition in Parkinson's disease: how can curcumin protect mitochondria?
Selective damage of mitochondrial complex I within the dopaminergic neurons of the substantia nigra is the central event during Parkinson disease. Peroxynitrite is one of the important free radicals probably mediating complex I damage. Peroxynitrite inhibits brain complex I mainly by 3-nitrotyrosine and nitrosothiol formation, but how these modifications alter the structure-function relation of complex I is unclear. Curcumin pretreatment protects brain mitochondria against peroxynitrite in vitro by direct detoxification and prevention of 3-nitrotyrosine formation and in vivo by elevation of total cellular glutathione levels. These results suggest a potential therapeutic role for curcumin against nitrosative stress in neurological disorders.


The Self-Perceived E-Learning Environment Scale: Development and Psychometric Properties in a Nursing Students Samples.
E-learning is increasingly used in education, creating a learning environment that needs to be studied thoroughly for developing new learning opportunities. Drawing from the community of inquiry framework, the present work provides the theoretical foundation and measurement validation of the Self-Perceived E-Learning Environment Scale (SEES). The SEES measures core aspects of the e-learning context: autonomous strategic planning, social interaction, and teacher feedback. Through two studies carried out in sample of nursing students, an exploratory (n = 302) and confirmatory (n = 245) factor analysis revealed a three-factor structure. The results provide empirical evidence of appropriate psychometric properties (i.e., reliability, validity). The SEES can be used in a higher education context, particularly in nursing education programs. Theoretical, methodological, and practical implications for exploring the e-learning environment in nursing educational settings are discussed.


Limitations and high pressure behavior of MOF-5 for CO2 capture.
Porous network structures (e.g. metal-organic frameworks, MOFs) show considerable potential in dethroning monoethanol amine (MEA) from being the dominant scrubber for CO2 at the fossil-fuel-burning power generators. In contrast to their promise, structural stability and high-pressure behavior of MOFs are not well documented. We herein report moisture stability, mechanical properties and high-pressure compression on a model MOF structure, MOF-5. Our results show that MOF-5 can endure all tested pressures (0-225 bar) without losing its structural integrity, however, its moist air stability points at a 3.5 hour safety window (at 21.6 °C and 49% humidity) for an efficient CO2 capture. Isosteric heats of CO2 adsorption at high pressures show moderate interaction energy between CO2 molecules and the MOF-5 sorbent, which combined with the large sorption ability of MOF-5 in the studied pressure-temperature ranges show the viability of this sorbent for CO2 capturing purposes. The combination of the physicochemical methods we used suggests a generalized analytical standard for measuring viability in CO2 capture operations.


Immune-mediated paraneoplasia.
Cancers induce a loss of homeostasis through the uncontrolled production and release of a variety of biologically active cellular products, natural compounds produced in unnatural quantities within abnormal anatomical locations. Often, there is an immune response to which the cancerous growth may succumb, or have the characteristics required to survive. If, during its proliferation, the cancer should coincidentally express a potent autoantigen then the organ in which that antigen is normally located may be damaged by the resultant immune response. Paradoxically, this aberrant immunological activity rarely has any appreciable inhibitory effects on the causal cancer. This inconsistency may result from the cancer's ability to block the host's immunological activity, while the affected organ situated elsewhere has no such capacity. Some predisposition, such as trauma to the affected organ, may prove a prerequisite that provides access to hitherto immunologically privileged sites. The effects of the subsequent loss of tolerance are often the first indication of a health problem, prompting the patient to seek medical help. Immune-mediated paraneoplasia is identified by antibody activity with any of a small but growing collection of organ-specific antigens demonstrated to have a distinct disease association and an apparent involvement in autoimmunity. Examples of the most common are described as introduction to this unusual collection of autoimmune diseases, for which in some cases the cause is known, and these may provide insight into the cause of those that are not.


Does provision of targeted health care for the unemployed enhance re-employment?
There is increasing pressure to develop services to enhance the health of the workforce on the periphery of the labour market. Health promotion among unemployed people may improve their health but also to increase their employability. We tested whether re-employment can be enhanced with a health care intervention targeted at the unemployed. A 3-year follow-up, controlled design was used. The data were collected among unemployed people (n = 539) participating in active labour market policy measures. The baseline survey included established habitually used health questionnaires. The intervention consisted of three health check-ups and on-demand health services. Logistic regression analyses were used to obtain the odds ratios of the intervention group versus control group for being re-employed at follow-up. Health-related differences in the re-employment effects of the intervention were assessed through the significance of the interaction in the regression analyses. The intervention did not serve to improve re-employment: at follow-up 50% of both the intervention group and the control group were at work. In further analyses, the odds ratios showed that the intervention tended to improve re-employment among participants in good health, whereas an opposite tendency was seen among those with poor health. The differences, however, were statistically non-significant. The experimental health service did not show any beneficial effects on re-employment. Nevertheless, rather than considering any particular health care as unnecessary and ineffective, we would like to stress the complexity of providing health services to match the diversity of the unemployed.


Foot dermatitis in children: causative allergens and follow-up.
Allergic contact dermatitis from shoes may have a typical pattern of presentation, but we have found that the distribution of dermatitis is often unhelpful in establishing the diagnosis. In this study, we aimed to define the features of foot dermatitis in children and to assess its outcome, in comparison to adults with foot eruptions. Relevant allergens were found in 15 out of 29 children and 26 out of 57 adults with foot eruptions. The most common allergens in children were rubber chemicals and topical medicaments. Adults showed a similar pattern, but also reacted to clothing dyes. The prognosis in both groups was good, with the dermatitis improving or resolving in 2/3.


Advantages of double releases in axillary, antecubital and popliteal contractures.
The advantages of the double release technique in axillary contractures are discussed. The procedure is useful for releasing contractures involving the antecubital and popliteal spaces as well. The risk of cutting vital structures involved in the scar tissue is minimized; also, the skin in the center of the axilla, if infected or ruptured, can be covered without as much threat to the axillary space. In addition, by placing the skin grafts on the surfaces at edges of the antecubital or in the popliteal space, the take of the skin graft on a flat surface is better insured.


Human neonatal lymphocytes immortalized after microinjection of Epstein-Barr virus DNA.
Epstein-Barr virus (EBV) is a highly efficient acute transforming agent in human cells, provided that the intact virus is used. To investigate the ability of viral DNA alone to transform cells, we introduced the EBV genome into human lymphocytes. After microinjection of EBV DNA into neonatal B lymphocytes, we established a cell line that in early passages contained multiple viral fragments. This cell line retained sequences from the short, unique (Us) region of the EBV genome and sequences from EcoRI-E. The viral sequences were not expressed; however, the cells expressed a 2.3-kilobase polyadenylated message homologous to the c-fgr oncogene, a cellular locus believed to be activated by EBV infection [M. S. C. Cheah, T. J. Ley, S. R. Tronick, and K. C. Robbins, Nature (London) 319:238-240.]. The cell line was monoclonal with rearrangement at the immunoglobulin locus and had a reciprocal translocation t(1;7)(p34;q34) and a deletion of sequences within the locus for the beta chain of the T-cell receptor. The close proximity of the translocation to the chromosomal loci for c-fgr on chromosome 1 and the T-cell receptor beta chain on chromosome 7 suggests that structural alteration of these genes was critical to this transformation event.


Neurofibromatosis and childhood tumors.
Although tumors are a known complication of von Recklinghausen's neurofibromatosis (NF), they often develop after the second decade and their characteristics in the pediatric population are unclear. To define the frequency and distribution of tumor types in children with NF, the authors reviewed the experience at Children's Hospital of Pittsburgh between 1953 and 1984. During that time, 121 children younger than 18 years with documented NF were seen. Three patients (2.5%) developed locally extensive, unresectable sarcomas, two of which were clearly neural in origin. Two other children died from complications of highly cellular but not histologically malignant neurofibromas. Seventeen patients (14%) had brain tumors, of which 3 (2.5%) were malignant astrocytomas and 9 were optic gliomas. Two children had acute myelogenous leukemia. Although it has been said that patients with NF are particularly susceptible to the oncogenic effects of radiation, 12 children were treated with a median of 5000 rad to their tumor bed. Follow-up after radiation in that small cohort of patients ranged from 6 months to 12 years (mean, 6 years). Eleven of 12 patients experienced adequate local control. During the follow-up period, none developed a second tumor outside or within the radiation port that could be related to radiation. The authors conclude that clinically significant tumors in children with NF, not all of which are histologically malignant, are not rare. Although more prospective information is needed on response to and sequelae from therapy, the data in this report suggest no contraindication to aggressive therapy.


Selective separation of hydroxide from alkaline nuclear tank waste by liquid-liquid extraction with weak hydroxy acids.
Recovery and recycle of caustic reagents in industrial processes offer potential means of pollution prevention, as investigated herein for particular needs related to the cleanup of alkaline nuclear waste. Specifically, the recovery of hydroxide from alkaline media by liquid-liquid extraction can be effected utilizing weak hydroxy acids, as demonstrated for NaOH utilizing a series of lipophilic fluorinated alcohols and alkylated phenols dissolved in 1-octanol. Extraction efficiency follows the expected order of acidity of the hydroxy acids, the phenols being the most efficient extractants among the compounds tested. After extraction, NaOH is effectively recoverable from the organic phase upon contact with water. The weakest hydroxy acids are the most efficiently stripped, NaOH recovery being nearly quantitative in a single contact. In competitive extraction experiments, good selectivity for hydroxide recovery over other anions such as nitrate and chloride was demonstrated. Since the order of extraction favors larger anions, the exceptional preference for hydroxide implies that the extraction occurs by deprotonation of the hydroxy acids in a cation-exchange process. Stripping therefore occurs by hydrolysis to regenerate the neutral hydroxy acid, liberating NaOH to the aqueous phase. Since hydroxide equivalents rather than actual hydroxide ions are transferred to the solvent, the process is termed "pseudohydroxide extraction." Hydroxide recovery from a simulant of alkaline nuclear tank waste (Hanford DSSF simulant) was also demonstrated in repeated extraction and stripping cycles.


Phosphatidylinositol Kinases and Phosphatases in Entamoeba histolytica.
Phosphatidylinositol (PtdIns) metabolism is indispensable in eukaryotes. Phosphoinositides (PIs) are phosphorylated derivatives of PtdIns and consist of seven species generated by reversible phosphorylation of the inositol moieties at the positions 3, 4, and 5. Each of the seven PIs has a unique subcellular and membrane domain distribution. In the enteric protozoan parasite Entamoeba histolytica, it has been previously shown that the PIs phosphatidylinositol 3-phosphate (PtdIns3P), PtdIns(4,5)P2, and PtdIns(3,4,5)P3 are localized to phagosomes/phagocytic cups, plasma membrane, and phagocytic cups, respectively. The localization of these PIs in E. histolytica is similar to that in mammalian cells, suggesting that PIs have orthologous functions in E. histolytica. In contrast, the conservation of the enzymes that metabolize PIs in this organism has not been well-documented. In this review, we summarized the full repertoire of the PI kinases and PI phosphatases found in E. histolytica via a genome-wide survey of the current genomic information. E. histolytica appears to have 10 PI kinases and 23 PI phosphatases. It has a panel of evolutionarily conserved enzymes that generate all the seven PI species. However, class II PI 3-kinases, type II PI 4-kinases, type III PI 5-phosphatases, and PI 4P-specific phosphatases are not present. Additionally, regulatory subunits of class I PI 3-kinases and type III PI 4-kinases have not been identified. Instead, homologs of class I PI 3-kinases and PTEN, a PI 3-phosphatase, exist as multiple isoforms, which likely reflects that elaborate signaling cascades mediated by PtdIns(3,4,5)P3 are present in this organism. There are several enzymes that have the nuclear localization signal: one phosphatidylinositol phosphate (PIP) kinase, two PI 3-phosphatases, and one PI 5-phosphatase; this suggests that PI metabolism also has conserved roles related to nuclear functions in E. histolytica, as it does in model organisms.


Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.
Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.


Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs.
Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example α1-3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking α1-3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper-immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking α1-3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection.


Impact of Nonpharmacological Interventions on Severe Acute Respiratory Infections in Children: From the National Surveillance Database.
Nonpharmacological interventions (NPIs) reduce the incidence of respiratory infections. After NPIs imposed during the coronavirus disease 2019 pandemic ceased, respiratory infections gradually increased worldwide. However, few studies have been conducted on severe respiratory infections requiring hospitalization in pediatric patients. This study compares epidemiological changes in severe respiratory infections during pre-NPI, NPI, and post-NPI periods in order to evaluate the effect of that NPI on severe respiratory infections in children. We retrospectively studied data collected at 13 Korean sentinel sites from January 2018 to October 2022 that were lodged in the national Severe Acute Respiratory Infections (SARIs) surveillance database. A total of 9,631 pediatric patients were admitted with SARIs during the pre-NPI period, 579 during the NPI period, and 1,580 during the post-NPI period. During the NPI period, the number of pediatric patients hospitalized with severe respiratory infections decreased dramatically, thus from 72.1 per 1,000 to 6.6 per 1,000. However, after NPIs ceased, the number increased to 22.8 per 1,000. During the post-NPI period, the positive test rate increased to the level noted before the pandemic. Strict NPIs including school and daycare center closures effectively reduced severe respiratory infections requiring hospitalization of children. However, childcare was severely compromised. To prepare for future respiratory infections, there is a need to develop a social consensus on NPIs that are appropriate for children.


Palladium-catalyzed regioselective hydroboration of aryl alkenes with B2pin2.
A palladium(ii)-catalyzed hydroboration of aryl alkenes with stable and easy-to-handle (pinacolato)diboron (B2pin2) under mild conditions has been developed. Acetic acid acted as the solvent and the hydrogen source, which has been identified by deuterium experiments. Notably, isomerization-hydroboration of allyl benzene derivatives was observed. As a result, a series of benzyl boronic esters were obtained in moderate to excellent yields with exclusive regioselectivity.


Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury.
Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho -0.33, P < 0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.


Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.
A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.


Micro-CT artifacts reduction based on detector random shifting and fast data inpainting.
In Micro-CT systems based on optical coupling detectors, the defects of scintillator or CCD-camera would lead to heavy artifacts in reconstructed CT images. Meanwhile, different detector units usually suffer from inhomogeneous response, which also leads to artifacts in the CT images. Detector shifting is a simple and efficient method to remove the artifacts due to inhomogeneous responses of detector units. However, it does not work well for heavy artifacts due to defects in scintillator or CCD. The purpose of this paper is to develop a data preprocessing method to reduce both kinds of artifacts. A hybrid method which involves detector random shifting and data inpainting is proposed to correct the projection data, so as to suppress the artifacts in the reconstructed CT images. The defects in scintillator or CCD-camera lead to data lost in some areas of the projection data. The Criminisi algorithm is employed to recover the lost data. By detector random shifting, the location of the lost data in one view might be shifted away in adjacent views. This feature is utilized to design the search window, such that the best match patch shall be searched across adjacent views. By this way, the best match patches should really enjoy high similarity. As a result, the heavy artifacts due to defects of scintillator or CCD-camera should be suppressed. Furthermore, a multiscale tessellation method is proposed to locate the defects and similarity patches, which makes the Criminisi algorithm very fast. The authors tested the proposed method on both simulated projection data and real projection data. Experiments show that the proposed method could correct the bad data in the projections quite well. Compared to other popular methods, such as linear interpolation, wavelet combining Fourier transform, and TV-inpainting, experimental results suggest that the CT images reconstructed from the preprocessed data sets by our method is significantly better in quality. They have proposed a hybrid method for projection data preprocessing which fits well to typical Micro-CT systems. The hybrid method could suppress the ring artifacts in the reconstructed CT images efficiently, while the spatial resolution is not reduced even with a critical eye.


Formation of block copolymer-protected nanoparticles via reactive impingement mixing.
Reactive impingement mixing was employed to produce polymer-protected nanoparticles. Amphiphilic block copolymer was formed in situ by reactive coupling of hydrophobic and hydrophilic blocks. Simultaneously, a hydrophobic compound and the copolymer coprecipitated to form nanoparticles in the range of 100 nm. Specifically, beta-carotene was stabilized by the amphiphilic diblock copolymer, formed from the reaction of an amino-terminated hydrophilic block, poly(ethylene glycol) (PEG-NH2), with an acid chloride-terminated hydrophobic block, either poly(epsilon-caprolactone) (PCL-COCl) or polystyrene (PS-COCl). Spherical particles were observed by scanning and cryogenic transmission electron microscopy. Process conditions, including feed concentration of beta-carotene and feed concentrations of polymeric stabilizers, had little or no effect on average particle sizes over the range studied. Further, for Reynolds numbers greater than 500 the feed flow rates also had no effect. The effect of glass transition temperature (Tg) of the hydrophobic polymer on morphology and particle formation mechanism is discussed.


A new species and two new records of Quercus (Fagaceae) from northern Vietnam.
A new species, Quercus xuanlienensis Binh, Ngoc & Bon, is described from Xuan Lien Nature Reserve, Vietnam. The new species is morphologically similar to Q. edithiae Skan, in having 8-11 pairs of secondary veins, bowl-shaped cupules and ellipsoid to cylindrical-ellipsoid and basally convex nuts. It differs in having serrulate leaf margins only at apical 1/5-1/7, almost entire margins of bracts on cupule and much longer nuts. The species is also similar to Q. fleuryi Hickel & A. Camus in having leaves glabrous on both surfaces with only an apically serrulate margin but differs in having shorter petioles, cupules enclosing 1/5 of the nut and much longer nuts. In addition, Q. disciformis Chun & Tsiang. and Q. bella Chun & Tsiang., previously known from China, are newly recorded from Ba Vi National Park, Vietnam.


Bald Eagle Nestling Mortality Associated with Argas radiatus and Argas ricei Tick Infestation and Successful Management with Nest Removal in Arizona, USA.
Eight Bald Eagle ( Haliaeetus leucocephalus ) nestlings heavily infested with larval ticks were found in or under a nest near the confluence of the Verde and Salt rivers in Arizona in 2009-11. The 8-12-wk-old nestlings were slow to respond to stimuli and exhibited generalized muscle weakness or paresis of the pelvic limbs. Numerous cutaneous and subcutaneous hemorrhages were associated with sites of tick attachment. Ticks were identified as Argas radiatus and Argas ricei. Treatment with acaricides and infection with West Nile virus (WNV) may have confounded the clinical presentation in 2009 and 2010. However, WNV-negative birds exhibited similar signs in 2011. One nestling recovered from paresis within 36 h after the removal of all adult and larval ticks (>350) and was released within 3 wk. The signs present in the heavily infested Bald Eagle nestlings resembled signs associated with tick paralysis, a neurotoxin-mediated paralytic syndrome described in mammals, reptiles, and wild birds (though not eagles). Removal of the infested nest and construction of a nest platform in a different tree was necessary to break the cycle of infection. The original nesting pair constructed a new nest on the man-made platform and successfully fledged two Bald Eagles in 2012.


Perceived Health Reporting Knowledge and News Gathering Practices of Health Journalists and Editors at Community Newspapers.
This research adds to our understanding of health and science reporting by identifying and examining the numbers, types, and simultaneous uses of resources selected by health and science journalists and editors at the initial stages of reporting, and relates this to journalists' perceived health reporting knowledge. A telephone survey of 141 health and science journalists and editors selected from 259 community newspapers in Missouri was conducted. Information sources included those that were highly credible, easy to access, already vetted by peers, and that enabled habitual reporting. Though the majority used multiple sources to generate story ideas, about one-third of respondents used no information sources. Journalists and editors' perceived health reporting knowledge acted as a trigger in prompting more reliance on a wider diversity of information sources, greater use of empirical evidence in health stories, and more time spent researching/writing health stories. Implications for community news organizations include education to improve actual and perceived knowledge of journalists on health and science information gathering.


Prognostic factors of stage Ib cervical carcinoma treated by radical abdominal hysterectomy.
From 1982 to 1984, 189 patients with stage Ib carcinoma of the uterine cervix underwent radical abdominal hysterectomies as primary treatment at Chang Gung Memorial Hospital. Of these patients, six were lost to follow-up. Nineteen of the 183 patients with regular follow-up recurred at intervals of from 9 to 55 months. An assessment of prognostic factors was made by reviewing the chart and pathological findings and correlating them with the patient's present status. Using univariate analysis, bulky tumor size was found to bear the greatest risk of tumor recurrence. Six of the 15 patients (40%) with a diameter of more than 4 cm recurred. The other risk factors included parametrial involvement, histologic type of adenosquamous or adenocarcinoma, lymph node metastasis, poor differentiation, deep cervical stromal invasion, and lymphatic or vascular space invasion. In conclusion, analysis of prognostic factors identified a group of patients at high risk of recurrence and decreased survival, for whom prospective trials of adjunctive treatment should be considered.


Atypical Spitz Nevi: A Case Report and Review of the Literature.
A case of atypical ("pagetoid") compound Spitz nevus on the face of a 2-year-old girl is reported with a review of the literature. The nevus was composed of broad but laterally demarcated compound proliferation of enlarged fusiform and epithelioid melanocytes, with florid pagetoid scatter above the junction. Immunohistochemical analyses revealed the Ki-67 proliferation index to be relatively low. Given the histomorphological overlap with melanoma, an array-based comparative genomic hybridization approach revealed a subthreshold gain in chromosome 1q and gain in distal chromosome 17q, with no other associated chromosomal gains or losses. These molecular aberrations suggested a partially transformed tumor, without adequate evidence for a molecular diagnosis of melanoma. Because of the diagnostic dilemma posed by these lesions, recent research has focused on molecular alterations that may help differentiate Spitz tumors from malignant melanomas.


Comparison of the effect of the chosen species of saprotrophic fungi on the development of Toxocara canis and Ascaris suum eggs.
The study aim was to compare the antagonistic interaction between saprotrophic soil fungi and embryonic development of geohelminths Toxocara canis and Ascaris suum. The experimental cultures were fertilized eggs of T.canis and A. suum incubated together with mycelium of strains: Fusarium culmorum, Metarhizium anisopliae,Paecilomyces fumosoroseus, Trichoderma viride and Trichothecium roseum. In the control cultures the eggs of both nematode species were incubated without fungi. The experiment was conducted at temp. 26°C for 60 days. Compared with the control, all of the tested species of fungi significantly extended the embryonic development of both T. canis and A. suum. Most inhibitory effect on the rate of embryonic development of T. canis and A. suum had three fungal species: P. fumosoreus, M. anisopliae and T. viride. Compared with the control, on the 60th day of incubation in the presence of each of the tested fungal species, a larger percentage (p<0.05) of morphological abnormalities was stated in developing embryos of T. canis (49–69%) than in A. suum (15.1–67.7%). Among the examined fungal species, only incubation with P. fumosoroseus resulted in significantly greater (p<0.05) incidence of embryonic malformations(embryopathies) in T. canis, as compared with A. suum. Also the percentage of dead larvae of T. canis in the control and in cultures with fungi (12% and 100%, respectively) was significantly higher in comparison with A. suum (0.5% and 10.3–36%, respectively). The highest percentage of non-viable larvae of A. suum was found in the presence of P.fumosoroseus, and the lowest in the presence of M. anisopliae. Findings may indicate that T. canis eggs are more sensitive to antagonistic interaction of the examined fungal strains than A. suum eggs.


II-BGlc, a glucose receptor of the bacterial phosphotransferase system: molecular cloning of ptsG and purification of the receptor from an overproducing strain of Escherichia coli.
The bacterial phosphoenolpyruvate:glycose phosphotransferase system (PTS) consists of interacting cytoplasmic and membrane proteins that catalyze the phosphorylation and translocation of sugar substrates across the cell membrane. One PTS protein, II-BGlc, is the membrane receptor specific for glucose and methyl D-glucopyranosides; the protein has been purified to homogeneity from Salmonella typhimurium [Erni, B., Trachsel, H., Postma, P. & Rosenbusch, J. (1982) J. Biol. Chem. 257, 13726-13730]. In the present experiments, the Escherichia coli ptsG locus, which encodes II-BGlc, was isolated from a transducing phage library and subcloned into plasmid vectors. The resulting plasmids complement the following phenotypic defects of ptsG mutants: growth on glucose, uptake and phosphorylation of methyl alpha-D-glucoside, and repression of the utilization of non-PTS sugars by methyl alpha-glucoside. The transformed cells overproduce II-BGlc 4- to 10-fold, and a Mr 43,000 polypeptide was synthesized from the plasmids in an in vitro transcription/translation system. The E. coli and S. typhimurium II-BGlc proteins differ in their physical properties, and a modified, three-step purification procedure was developed for isolating the E. coli protein.


Direct quantitative determination of amlodipine enantiomers in urine samples for pharmacokinetic study using on-line coupled isotachophoresis-capillary zone electrophoresis separation method with diode array detection.
The present work illustrates possibilities of column-coupling capillary electrophoresis (CE-CE) combined with chiral selector (2-hydroxypropyl-beta-cyclodextrin, HP-beta-CD) and fiber-based diode array detection (DAD) for the direct quantitative enantioselective determination of trace drug (amlodipine, AML) in biological multicomponent ionic matrices (human urine). Capillary isotachophoresis (ITP) served as an ideal injection technique in CE-CE. Moreover, the ITP provided an effective on-line sample pretreatment prior to the capillary zone electrophoresis (CZE) separation. Enhanced separation selectivity due to the combination of different separation mechanisms (ITP vs. CZE-HP-beta-CD) enabled to obtain pure zones of the analytes, suitable for their detection and quantitation. The DAD, unlike single wavelength UV detection, enabled to characterize the purity (i.e. spectral homogeneity) of the analytes zones. A processing of the raw DAD spectra (the background correction and smoothing procedure) was essential when a trace analyte signal was evaluated. Obtained results indicated pure (i.e. spectrally homogeneous) zones of interest confirming effective ITP-CZE separation process. The proposed ITP-CZE-DAD method was characterized by favorable performance parameters (sensitivity, linearity, precision, recovery, accuracy, robustness, selectivity) and successfully applied to an enantioselective pharmacokinetic study of AML.


[Nutritional status of institutionalized Venezuelan elderly].
With the aim of evaluating the nutritional status of institutionalized elders in different geriatric units of the metropolitan area of Caracas, 126 subjects with ages between 60 and 96 years old were evaluated. The Mini Nutritional Assessment was applied and were identified 48.4% individuals with nutritional risk, 5.6% malnourished and 46% without nutritional problems. Females presented higher prevalences of malnutrition and risk, while males presented an adequate nutritional state. By sex and age, females and males over 80 years presented a higher prevalence of malnutrition and risk when they were compared whit those younger. A low dayly liquid intake, a BMI equal or under of 23 kg/m2 and a limited physical performance were the items that presented the highest prevalence among the studied elders. In conclusion, the high prevalence of malnutrition risk in this population group, remarks the necessity to include into the global geriatric evaluation, a quick, simple and non-invasive instrument that allows to estimate the nutritional status of the elders.


Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry-Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors.
We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.


Bullet embolisation from injured inferior cava vein to the right ventricle.
Gunshot injuries of the human body challenge surgical teams in the emergency department. Since such injuries do not follow any rule, every patient should be considered a special case. Our case, of bullet embolism from injured inferior cava vein to the right heart ventricle is a rare one. Such cases make us be more alert for diagnosis and treatment of this kind of injury. Well equipped hospitals and experienced medical teams are necessary for successful outcome.


The role of DNA damage in the resistance of human chronic myeloid leukemia cells to cyclophosphamide analogues.
We examined 4-hydroperoxycyclophosphamide (4HC) and phosphorodiamidic mustard (PM)-mediated cytotoxicity and DNA interstrand cross-link (ISC) induction in a 4HC-resistant subline, B5-180(3), that was derived from the subcloned human myeloid leukemia cell line KBM-7/B5. Based on the ratio of the 50% inhibitory concentration values, B5-180(3) cells were approximately 35-fold resistant to 4HC compared with the parental cells. 4HC-induced ISC levels (as measured by alkaline elution) were approximately 9-fold lower in the 4HC-resistant line than the parent line. To determine whether the approximately 9-fold reduction of initial 4HC-induced ISCs was related to elevated aldehyde dehydrogenase (ADH), we examined PM-mediated cytotoxicity and ISC induction in the two cell lines. Unlike 4HC, the cytotoxicity of PM is independent of ADH activity. B5-180(3) cells were between 5- and 7-fold resistant to the cytotoxic effects of PM and were only slightly (approximately 1.3-fold) resistant to PM-mediated ISC induction. Furthermore, when cells were exposed to 4HC in the presence of 40 micrograms/ml cyanamide, an efficient inhibitor of ADH, the resistance index based on the 50% inhibitory concentration values was decreased to approximately 8. Elevated ADH can therefore explain most of the decrease in 4HC-induced ISCs, with elevated GSH levels probably accounting for the remaining small increment of resistance. Thus, decreased levels of ISC induction can account for a factor of approximately 9 of the total approximately 35-fold resistance to 4HC. The remaining increment of resistance to 4HC, as well as the cross-resistance to PM, appears to relate to an enhanced ability of the resistant subline to tolerate drug-induced ISCs. Thus, multiple factors appear to be involved in the resistance of these cells to the cytotoxic and DNA-damaging effects of 4HC, with elevated ADH and temporal factors (related to the processing of DNA damage) being the most important of these.


[Safety of diagnostic transradial catheterization in patients undergoing long-term anticoagulation with coumarin derivatives].
The aim of this study was to evaluate the safety of transradial catheterization without prior withdrawal of oral anticoagulation. In total, 183 patients on long-term acenocoumarol treatment who underwent transradial catheterization were included in a prospective study. In 135 patients, the coumarin derivative was continued without interruption before and during catheterization and, in 48, the drug was stopped 48 hours in advance. No severe thromboembolic or hemorrhagic complications occurred. At 7-day follow-up, the rate of occurrence of hematomas >3 cm in size was 5.5% in the group that continued anticoagulant treatment, and 10.4% in the group that stopped oral anticoagulation (P=.31). The transradial approach appears to be a safe option for patients receiving long-term coumarin treatment and could be the technique of choice because it avoids the drawbacks and complications associated with the withdrawal of oral anticoagulation.


Equation-of-motion spin-flip coupled-cluster model with single and double substitutions: Theory and application to cyclobutadiene.
While the equation-of-motion coupled-cluster (EOM-CC) method is capable of describing certain multiconfigurational wave functions within a single-reference framework (e.g., open-shell type excited states, doublet radicals, etc.), it may fail in cases of more extensive degeneracy, e.g., bond breaking and polyradicals. This work presents an extension of the EOM-CC approach to these chemically important situations. In our approach, target multiconfigurational wave functions are described as spin-flipping excitations from the high-spin reference state. This enables a balanced treatment of nearly degenerate electronic configurations present in the target low-spin wave functions. The relations between the traditional spin-conserving EOM models and the EOM spin-flip method is discussed. The presentation of the formalism emphasizes the variational properties of the theory and shows that the killer condition is rigorously satisfied in single-reference EOM-CC theories. The capabilities and advantages of the new approach are demonstrated by its application to cyclobutadiene.


Automated mammographic breast density estimation using a fully convolutional network.
The purpose of this study was to develop a fully automated algorithm for mammographic breast density estimation using deep learning. Our algorithm used a fully convolutional network, which is a deep learning framework for image segmentation, to segment both the breast and the dense fibroglandular areas on mammographic images. Using the segmented breast and dense areas, our algorithm computed the breast percent density (PD), which is the faction of dense area in a breast. Our dataset included full-field digital screening mammograms of 604 women, which included 1208 mediolateral oblique (MLO) and 1208 craniocaudal (CC) views. We allocated 455, 58, and 91 of 604 women and their exams into training, testing, and validation datasets, respectively. We established ground truth for the breast and the dense fibroglandular areas via manual segmentation and segmentation using a simple thresholding based on BI-RADS density assessments by radiologists, respectively. Using the mammograms and ground truth, we fine-tuned a pretrained deep learning network to train the network to segment both the breast and the fibroglandular areas. Using the validation dataset, we evaluated the performance of the proposed algorithm against radiologists' BI-RADS density assessments. Specifically, we conducted a correlation analysis between a BI-RADS density assessment of a given breast and its corresponding PD estimate by the proposed algorithm. In addition, we evaluated our algorithm in terms of its ability to classify the BI-RADS density using PD estimates, and its ability to provide consistent PD estimates for the left and the right breast and the MLO and CC views of the same women. To show the effectiveness of our algorithm, we compared the performance of our algorithm against a state of the art algorithm, laboratory for individualized breast radiodensity assessment (LIBRA). The PD estimated by our algorithm correlated well with BI-RADS density ratings by radiologists. Pearson's rho values of our algorithm for CC view, MLO view, and CC-MLO-averaged were 0.81, 0.79, and 0.85, respectively, while those of LIBRA were 0.58, 0.71, and 0.69, respectively. For CC view and CC-MLO averaged cases, the difference in rho values between the proposed algorithm and LIBRA showed statistical significance (P < 0.006). In addition, our algorithm provided reliable PD estimates for the left and the right breast (Pearson's ρ > 0.87) and for the MLO and CC views (Pearson's ρ = 0.76). However, LIBRA showed a lower Pearson's rho value (0.66) for both the left and right breasts for the CC view. In addition, our algorithm showed an excellent ability to separate each sub BI-RADS breast density class (statistically significant, p-values = 0.0001 or less); only one comparison pair, density 1 and density 2 in the CC view, was not statistically significant (P = 0.54). However, LIBRA failed to separate breasts in density 1 and 2 for both the CC and MLO views (P > 0.64). We have developed a new deep learning based algorithm for breast density segmentation and estimation. We showed that the proposed algorithm correlated well with BI-RADS density assessments by radiologists and outperformed an existing state of the art algorithm.


Team Reasoning and Collective Intentionality.
Different versions of the idea that individualism about agency is the root of standard game theoretical puzzles have been defended by Regan 1980, Bacharach (Research in Economics 53: 117-147, 1999), Hurley (Behavioral and Brain Sciences 26: 264-265, 2003), Sugden (Philosophical Explorations 6(3):165-181, 2003), and Tuomela 2013, among others. While collectivistic game theorists like Michael Bacharach provide formal frameworks designed to avert some of the standard dilemmas, philosophers of collective action like Raimo Tuomela aim at substantive accounts of collective action that may explain how agents overcoming such social dilemmas would be motivated. This paper focuses on the conditions on collective action and intention that need to be fulfilled for Bacharach's "team reasoning" to occur. Two influential approaches to collective action are related to the idea of team reasoning: Michael Bratman's theory of shared intention and Raimo Tuomela's theory of a we-mode of intending. I argue that neither captures the "agency transformation" that team reasoning requires. That might be an acceptable conclusion for Bratman but more problematic for Tuomela, who claims that Bacharach's results support his theory. I sketch an alternative framework in which the perspectival element that is required for team reasoning - the 'we-perspective' - can be understood and functionally characterized in relation to the traditional distinction between mode and content of intentional states. I claim that the latter understanding of a collective perspective provides the right kind of philosophical background for team reasoning, and I discuss some implications in relation to Tuomela's assumption that switching between individual and collective perspectives can be a matter of rational choice.


Predictive Growth Model of Listeria monocytogenes Under Fluctuating Temperature Conditions in Pasteurized Milk by Using Real-Time Polymerase Chain Reaction.
The aim of this study was to evaluate the application of real-time polymerase chain reaction (PCR)-based quantification as a rapid and accurate tool for the monitoring and prediction of Listeria monocytogenes growth in pasteurized milk under constant and fluctuating temperature conditions. The growth of L. monocytogenes was monitored under constant temperature conditions at 4°C, 10°C, 15°C, 20°C, and 35°C. High correlation was obtained between the bacterial growth rate and incubation temperature, where the R2 of the slope of the square root model was calculated to be 0.993 and 0.996 for real-time PCR and the conventional culture method, respectively. Moreover, the obtained maximum specific growth rate (μmax) data plots were correlated with 188 L. monocytogenes μmax data points from the existing model according to ComBase database, with an R2 of 0.961 for real-time PCR and of 0.931 for the conventional culture method. The growth models were examined under three different patterns of fluctuating temperature conditions ranging from 2°C to 30°C. The prediction results fell within ±20% of the relative error zone, showing that real-time PCR quantification could be used for fast, sensitive, and specific bacterial growth monitoring with high-throughput results. Real-time PCR should be considered a promising option and powerful tool for the construction of a bacterial growth prediction model for safety risk analysis in the dairy industry.


Effect of acupuncture inclusion in the enhanced recovery after surgery protocol on tumor patient gastrointestinal function: a systematic review and meta-analysis of randomized controlled studies.
Acupuncture has been shown to be effective in restoring gastrointestinal function in tumor patients receiving the enhanced recovery after surgery (ERAS) protocol. The present systematic review and meta-analysis aimed to evaluate the rationality and efficacy of integrating acupuncture in the ERAS strategy to recuperate gastrointestinal function. We searched eleven databases for relevant randomized clinical trials (RCTs) of acupuncture for the treatment of gastrointestinal dysfunction in tumor patients treated with the ERAS protocol. The quality of each article was assessed using the Cochrane Collaboration risk of bias criteria and the modified Jadad Scale. As individual symptoms, the primary outcomes were time to postoperative oral food intake, time to first flatus, time to first distension and peristaltic sound recovery time (PSRT). Pain control, adverse events, and acupoint names reported in the included studies were also investigated. Of the 211 reviewed abstracts, 9 studies (702 patients) met eligibility criteria and were included in the present systematic review and meta‑analysis. Compared to control groups, acupuncture groups showed a significant reduction in time to postoperative oral food intake [standardized mean difference (SMD) = -0.77, 95% confidence interval (CI) -1.18 to -0.35], time to first flatus (SMD=-0.81, 95% CI -1.13 to -0.48), time to first defecation (SMD=-0.91, 95% CI -1.41 to -0.41, PSRT (SMD=-0.92, 95% CI -1.93 to 0.08), and pain intensity (SMD=-0.60, 95% CI -0.83 to -0.37).The Zusanli (ST36) and Shangjuxu (ST37) acupoints were used in eight of the nine included studies. Adverse events related to acupuncture were observed in two studies, and only one case of bruising was reported. The present systematic review and meta‑analysis suggested that acupuncture significantly improves recovery of gastrointestinal function and pain control in tumor patients receiving the ERAS protocol compared to the control group. Moreover, ST36 and ST37 were the most frequently used acupoints. Although the safety of acupuncture was poorly described in the included studies, the available data suggested that acupuncture is a safe treatment with only mild side effects. These findings provide evidence-based recommendations for the inclusion of acupuncture in the ERAS protocol for tumor patients. https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023430211.


Targeting Immune-Mediated Dormancy: A Promising Treatment of Cancer.
Immune-mediated dormancy is when the immune system keeps proliferating tumor cells unchanged, mostly via cytotoxic activity of immune cells. Cancer dormancy, especially immune-mediated dormancy, may be the explanation for tumor refractory and may be responsible for resistance to conventional chemo- and radiotherapies. Here, we will describe different scenarios as to how the immune cells and cytokines involved in cancer progression are connected with the initiation of dormancy and cancer treatment. Two distinct treatment methods, such as maintaining metastatic tumor cells dormant and awakening them, are also discussed. A better understanding of immune-mediated dormancy will help to design novel and effective immunotherapies and will likely increase the efficiency of tumor treatment inhibiting metastasis.


Hormonal contraceptive use before hCG remission does not increase the risk of gestational trophoblastic neoplasia following complete hydatidiform mole: a historical database review.
To re-evaluate the safety of hormonal contraceptives (HC) after uterine evacuation of complete hydatidiform mole (CHM). Historical database review. Charing Cross Hospital Gestational Trophoblastic Disease Centre, London, United Kingdom. Two thousand four hundred and twenty-three women with CHM of whom 154 commenced HC while their human chorionic gonadotropin (hCG) was still elevated, followed between 2003 and 2012. We compared time to hCG remission between HC users and nonusers. The relationship between HC use and gestational trophoblastic neoplasia (GTN) development was assessed. The relationship between HC use and a high International Federation of Gynecology and Obstetrics (FIGO) risk score was determined. Time to hCG remission, risk of developing postmolar GTN and proportion of women with high FIGO risk score. No relationship was observed between HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P = 0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15). Moreover, no association between HC and GTN development was found, even when an age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). The use of current HC is not associated with development of postmolar GTN or delayed time to hCG remission. Therefore, HC can be safely used to prevent a new conception following CHM regardless of hCG level. Non-concurrent cohort study to re-evaluate the safety of low dose HCs after uterine evacuation of CHM.


A new biosensor for specific determination of glucose or fructose using an oxidoreductase of Zymomonas mobilis.
Cells of Zymomonas mobilis were permeabilized with toluene in order to utilize the enzymes, glucose-fructose oxidoreductase and gluconolactonase, inside the intact cells. Permeabilized cells were immobilized in a gelatin membrane, and a whole cell enzyme electrode was constructed by fixing the membrane on pH electrode. The biosensor developed was used for specific determination of glucose or fructose by detecting the production rate of hydrogen ion. Optimum conditions for biosensor response were pH 6.2 and temperature of 39 degrees C. The biosensor was highly specific and reproducible, and calibration curves for glucose and fructose were excellent, being linear up to 5 and 50 g/L, respectively.


Localization using nonindividualized head-related transfer functions.
A recent development in human-computer interfaces is the virtual acoustic display, a device that synthesizes three-dimensional, spatial auditory information over headphones using digital filters constructed from head-related transfer functions (HRTFs). The utility of such a display depends on the accuracy with which listeners can localize virtual sound sources. A previous study [F. L. Wightman and D. J. Kistler, J. Acoust. Soc. Am. 85, 868-878 (1989)] observed accurate localization by listeners for free-field sources and for virtual sources generated from the subjects' own HRTFs. In practice, measurement of the HRTFs of each potential user of a spatial auditory display may not be feasible. Thus, a critical research question is whether listeners can obtain adequate localization cues from stimuli based on nonindividualized transforms. Here, inexperienced listeners judged the apparent direction (azimuth and elevation) of wideband noisebursts presented in the free-field or over headphones; headphone stimuli were synthesized using HRTFs from a representative subject of Wightman and Kistler. When confusions were resolved, localization of virtual sources was quite accurate and comparable to the free-field sources for 12 of the 16 subjects. Of the remaining subjects, 2 showed poor elevation accuracy in both stimulus conditions, and 2 showed degraded elevation accuracy with virtual sources. Many of the listeners also showed high rates of front-back and up-down confusions that increased significantly for virtual sources compared to the free-field stimuli. These data suggest that while the interaural cues to horizontal location are robust, the spectral cues considered important for resolving location along a particular cone-of-confusion are distorted by a synthesis process that uses nonindividualized HRTFs.


Water-solid interactions. III. Effect of glass transition temperature, Tg, and processing on tensile strength of compacts of lactose and lactose/polyvinyl pyrrolidone.
The effect of moisture sorption at different relative humidities on the tensile strength and the physical stability of compacts of crystalline and partly amorphous lactose, alone and in binary mixtures with PVP, has been studied. Furthermore, the role of moisture as a plasticizer and its effect on the glass transition temperature, Tg, are related to the compactibiltiy. Samples were conditioned for 2 hr using a climate test chamber at different relative humidities. Moisture sorption was determined, the radial crushing strength for compacts was measured immediately and after storage, and the tensile strength was calculated. The glass transition temperature, Tg, was determined using DSC. The tensile strength of the compacts was found to depend on both the conditioning humidity and the humidity during storage. An increase in humidity to a level at which the glass transition temperature, Tg, fell below the operating temperature, T, resulted in transition from a rigid glassy state to a mobile rubbery state. For compacts of partly amorphous lactose, an increase in the tensile strength was observed during storage of tablets, due to recrystallization of the amorphous regions above Tg. Tablets of mixtures of lactose and PVP exhibit a sharp decrease in tensile strength at humidities above 70% RH, due to the glass-to-rubber transition of PVP.


Meta-analysis of magnetic resonance imaging accuracy for diagnosis of oral cancer.
To establish the diagnostic accuracy of magnetic resonance imaging (MRI) as an auxiliary means for the diagnosis of oral cancer through a systematic review and meta-analysis. An exhaustive search of publications from 1986 to 2016 was performed of Medline, Embase and Cochrane (and related databases), including grey literature. Primary diagnostic accuracy studies that assessed oral cancer (target condition) using MRI (index test) were included. Diagnostic threshold, sensitivity and meta-regression analyses were performed. A meta-analysis was performed using Meta-DiSc® v. 1.4 software. A total of 24 primary studies were assessed, comprising 1,403 oral cancer lesions. Nine studies used diffusion-weighted MRI, with a diagnostic odds ratio (DOR) of 30.7 (95% confidence interval [CI]: 12.7-74.3) and area under the curve (AUC) of 0.917 (95% CI: 0.915-0.918); seven studies used dynamic contrast-enhanced MRI, with a DOR of 48.1 (95%CI: 22.4-103.2) and AUC of 0.936 (95% CI: 0.934-0.937); and 13 studies used traditional MRI, with a DOR of 23.9 (95%CI: 13.2-43.3) and AUC of 0.894 (95% CI: 0.894-0.895). Meta-regression analysis indicated that the magnetic field strength may have influenced the heterogeneity of the results obtained (p = 0.0233) using traditional MRI. Sensitivity analysis revealed a discrete reduction of inconsistency in some subgroups. The three types of MRI assessed exhibited satisfactory accuracy compared to biopsy. Considering the relevance of early treatment and screening and that better health care results in improved survival rates and quality of life for oral cancer patients, we suggest the use of MRI as a part of the pre-treatment and monitoring protocol at public health services.


Alteration in the expression of endothelial cell integrin receptors alpha 5 beta 1 and alpha 2 beta 1 and alpha 6 beta 1 after in vitro infection with a clinical isolate of human cytomegalovirus.
Human cytomegalovirus infection of human umbilical vein endothelial cells reduces the ability of these cells to bind to fibronectin, collagen type IV and laminin. This suppression requires active virus, since UV-inactivated virus did not alter the binding ability of these cells to adhere to fibronectin, collagen type IV, and laminin. In an attempt to elucidate the molecular mechanism of this altered interaction, the surface expression of alpha 5 beta 1, alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 integrins on cytomegalovirus-infected endothelial cells was examined using attachment inhibition assay and flow cytometric analysis. The results presented here show that infection with human cytomegalovirus selectively alters the expression of integrin on human endothelial cells, with the ability to induce downregulation of alpha 5 beta 1 and alpha 2 beta 1 (p = 0.001) and p = 0.03, respectively), while significantly upregulating alpha 6 beta 1 (p = 0.03), and marginally upregulating alpha 3 beta 1 (p = 0.05).


A New Method to Overcome Carboxyamide Formation During AFEX Pretreatment of Lignocellulosic Biomass.
Lignin-carbohydrate complexes (LCCs) in the plant cell wall are responsible for providing resistance against biomass-degrading enzymes produced by microorganisms. Four major types of lignin-carbohydrate bonds are reported in the literature, namely, benzyl ethers, benzyl esters, phenyl glycosides, and acetyl ester linkages. Ester's linkages in the plant cell wall are labile to alkaline pretreatments, such as ammonia fiber expansion (AFEX), which uses liquid or gaseous ammonia to cleave those linkages in the plant cell wall and reduce biomass recalcitrance. Two competing reactions, notably hydrolysis and ammonolysis, take place during AFEX pretreatment process, producing different aliphatic and aromatic acids, as well as their amide counterparts. AFEX pretreated grasses and agricultural residues are known to increase conversion of biomass to sugars by four- to five-fold when subjected to commercial enzyme hydrolysis, yielding a sustainable feedstock for producing biofuels, biomaterials, and animal feed. Animal feed trials on dairy cows have demonstrated a 27% increase in milk production when compared to a control feedstock. However, the presence of carboxamides in feedstocks could promote neurotoxicity in animals if consumed beyond a certain concentration. Thus, there is the need to overcome regulatory hurdles associated with commercializing AFEX pretreated biomass as animal feed in the United States. This manuscript demonstrates a modified pretreatment for increasing the digestibility of industrial byproducts such as Brewer's spent grains (BSG) and high-fiber meal (HFM) produced from BSG and dry distillers grains with soluble (DDGS), while avoiding the production of carboxamides. The three industrial byproducts were first treated with calculated amounts of alkali such as NaOH, Ca(OH)2, or KOH followed by AFEX pretreatment. We found that 4% alkali was able to de-esterify BSG and DDGS more efficiently than using 2% alkali at both 10 and 20% solids loading. AFEX pretreatment of de-esterified BSG, HFM, and DDGS produced twofold higher glucan conversion than respective untreated biomass. This new discovery can help overcome potential regulatory issues associated with the presence of carboxamides in ammonia-pretreated animal feeds and is expected to benefit several farmers around the world.