Heart failure and sleep apnea: emphasis on practical therapeutic options.
Heart failure is a highly prevalent problem associated with excess morbidity and mortality and economic impact. Because of increased average life span, improved therapy of ischemic coronary artery disease and hypertension, the incidence and prevalence of heart failure will continue to rise into the twenty-first century. Multiple factors may contribute to the progressively declining course of heart failure. One such cause could be the occurrence of repetitive episodes of apnea, hypopnea, and hyperpnea, which frequently occur in patients with heart failure. Episodes of apnea, hypopnea, and hyperpnea cause sleep disruption, arousals, intermittent hypoxemia, hypercapnia, hypocapnia, and changes in intrathoracic pressure. These pathophysiologic consequences of sleep-related breathing disorders have deleterious effects on cardiovascular system, and the effects may be most pronounced in the setting of established heart failure and coronary artery disease. Diagnosis and treatment of sleep-related breathing disorders may improve morbidity and mortality of patients with heart failure [34]. Large-scale, carefully executed therapeutic studies are needed to determine if treatment of sleep-related breathing disorders changes the natural history of left ventricular failure.


Inhibitory effect of GLP-1 on gastric motility persists after vagal deafferentation in pigs.
Glucagon-like peptide 1 (GLP-1) is an intestinal hormone that is secreted in response to meal ingestion. GLP-1 inhibits gastric emptying and reduces postprandial gastric secretion and may play a physiological regulatory role in controlling appetite and energy intake in humans. The GLP-1 receptors have been identified in several organs including the stomach, brain and pancreas. The GLP-1 mechanism of action on insulin secretion is at least partly mediated via receptors on the pancreatic islet, but the mechanism by which GLP-1 retards gastric emptying is not known and may involve neural interactions, although GLP-1 has no effect on vagally stimulated motor activity of the isolated porcine antrum. Previously, an experimental model was developed with centrally (insulin hypoglycaemia) induced vagally mediated stimulation of antral motility, recorded by force transducers, in anaesthetized pigs. This model has now been developed further to include vagal deafferentation to determine the role of the afferent vagus in mediating the inhibitory effect of GLP-1 on gastric motility. Intravenous infusion of GLP-1 resulting in slightly supraphysiological plasma levels inhibited the antral contractile force, with the amplitude falling from 29.9+/-5.7 mm to 14.6+/-3.5 mm (p<0.001). After vagal deafferentation GLP-1 still inhibited antral motility (from 36.6+/-6.4 mm to 25+/-4.4 mm (p<0.019). The decrease in amplitude was the same before and after deafferentation. GLP-1 significantly inhibited centrally induced antral motility and the inhibitory effect of GLP-1 on gastric motility persisted after vagal deafferentation, supporting the hypothesis that the inhibitory effect results from direct interaction of GLP with receptors in the CNS, which in turn reduce vagal efferent output.


Magnetic resonance imaging of knee injuries in children.
The appearances of knee injuries on MR imaging are less well documented in children than adults. Some patterns of injury are shared by both groups of patients, e. g. meniscal damage. The frequency of specific injuries may differ, e. g. anterior cruciate ligament (ACL) tear. Congenital abnormality, coexistent pathology and previous treatment of the knee appear to be associated with meniscal problems. Discoid menisci are seen most frequently in children and have unique features on MR scans. Cruciate ligament tears are difficult to diagnose in the smallest children. The ACL may not be identified due to its small size. Normal bone marrow signal may be confused with marrow infiltration or bone microfracture. Radiographically occult fractures around the knee appear to be strongly associated with ligamentous injury as in adult patients. Osteochondral fractures, osteochondral lesions and articular cartilage damage are revealed on MR scans, but their long-term effects are uncertain. It is possible to diagnose a range of knee injuries on MR scans in children. The biggest diagnostic challenge is in pre-school children.


Transverse and normal interfacial stiffness of solids with randomly rough surfaces.
Using a theoretical approach and computer simulations, we calculate the normal stiffness K(perpendicular) and the transverse stiffness K(parallel) of the interface between two contacting isotropic solids with randomly rough surfaces and Poisson ratio ν. The theoretical predictions for K(perpendicular) agree well with the simulations. Moreover, the theoretical result for the ratio K(perpendicular)/K(parallel) is (2 - ν)/(2 - 2ν), as predicted by Mindlin for a single circular contact region. Finally, we compare the theory to experimental ultrasonic data.


Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds.
Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications.


The impaired quorum sensing response of Pseudomonas aeruginosa MexAB-OprM efflux pump overexpressing mutants is not due to non-physiological efflux of 3-oxo-C12-HSL.
Multidrug (MDR) efflux pumps are ancient and conserved molecular machineries with relevant roles in different aspects of the bacterial physiology, besides antibiotic resistance. In the case of the environmental opportunistic pathogen Pseudomonas aeruginosa, it has been shown that overexpression of different efflux pumps is linked to the impairment of the quorum sensing (QS) response. Nevertheless, the causes of such impairment are different for each analysed efflux pump. Herein, we performed an in-depth analysis of the QS-mediated response of a P. aeruginosa antibiotic resistant mutant that overexpresses MexAB-OprM. Although previous work claimed that this efflux pump extrudes the QS signal 3-oxo-C12-HSL, we show otherwise. Our results evidence that the observed attenuation in the QS response when overexpressing this pump is related to an impaired production of alkyl quinolone QS signals, likely prompted by the reduced availability of one of their precursors, the octanoate. Together with previous studies, this indicates that, although the consequences of overexpressing efflux pumps are similar (impaired QS response), the underlying mechanisms are different. This 'apparent redundancy' of MDR efflux systems can be understood as a P. aeruginosa strategy to keep the robustness of the QS regulatory network and modulate its output in response to different signals.


Clinical applications of flow karyotyping in myelocytic leukemia by stimulation of different subpopulations of cells in blood or bone marrow samples.
Examples are presented in which normal as well as abnormal chromosome distributions could be obtained from the same individual by means of bivariate flow karyotyping. Selective stimulation of T-lymphocytes obtained by E-rosetting from the blood of a patient with acute myelocytic leukemia resulted in a normal flow karyogram. The specific stimulation of myelocytic leukemia cells with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) yielded flow karyograms displaying the leukemia-associated chromosome abnormalities. The resulting flow karyograms could be used to discriminate between homolog differences, which appear normally in virtually every individual, and leukemia-associated chromosomal aberrations. In the case of a female chronic myelocytic leukemia patient who received bone marrow form an HLA-identical male donor, specific stimulation of various subsets of cells enabled to discriminate between leukemic host cells and non-leukemic donor cells. Both the leukemia-specific translocations and sex chromosomes were used as markers to analyse the flow karyograms obtained from the same sample.


Antileishmanial activity of 4-phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) derivative on Leishmania amazonensis and Leishmania braziliensis: In silico ADMET, in vitro activity, docking and molecular dynamic simulations.
Organic compounds obtained by click chemistry reactions have demonstrated a broad spectrum of biological activities being widely applied for the development of molecules against pathogens of medical and veterinary importance. Cutaneous leishmaniasis (CL), caused by intracellular protozoa parasite of genus Leishmania, comprises a complex of clinical manifestations that affect the skin and mucous membranes. The available drugs for the treatment are toxic and costly, with long periods of treatment, and the emergence of resistant strains has been reported. In this study we investigated the in vitro effects of a phthalimide-1,2,3-triazole derivative, the 4-Phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) obtained by click chemistry, on mammalian cells and on L. amazonensis and L. braziliensis, the causative agents of CL in Brazil. In silico ADMET evaluation of PT4 showed that this molecule has good pharmacokinetic properties with no violation of Lipinski's rules. The in vitro assays showed that PT4 was more selective for both Leishmania species than to mammalian cells. This compound also presented low cytotoxicity to mammalian cells with CC50 > 500 μM. Treatment of promastigote forms with different concentrations of PT4 resulted in ultrastructural alterations, such as plasma membrane wrinkling, shortening of cell body, increased cell volume and cell rupture. The molecular dynamic simulations showed that PT4 interacts with Lanosterol 14 α-demethylase from Leishmania, an essential enzyme of lipid synthesis pathway in this parasite. Our results demonstrated PT4 was effective against both species of Leishmania. PT4 caused a decrease of mitochondrial membrane potential and increased production of reactive oxygen species, which may lead to parasite death. Taken together, our results pointed PT4 as promissing therapeutic agent against CL.


Personality variables in risk perception, learning and risky choice after safety training: Data of two empirical intervention studies contrasting immersive VR and PowerPoint.
The data provided contains personality variables as well as risk perception, choice data and learning outcomes after safety training which differed between subject regarding whether it was carried out in immersive virtual reality (VR) or as a PowerPoint. The data presented here is reported in the study of Leder et al. (in press) [3] where the impact of presentation medium on safety training effectiveness was investigated. The data is hosted on the open science project: https://osf.io/rxq5w/?view_only=cd42aa4b97514f16af8884697450d2a6.


Screening for depression with the PHQ-9 in young adults affected by HIV.
Major depressive disorder (MDD) is common among young adults with perinatally acquired HIV (YAPHIV), however it is often underdiagnosed and untreated. The PHQ-9 and PHQ-2 are widely used screening instruments for MDD. This study evaluates the accuracy of recommended PHQ-9 and PHQ-2 cut-scores of 10 and 3 for YAPHIV and YA who were perinatally HIV exposed but uninfected (YAPHEU). The PHQ-9 was administered to participants (n = 203) in a longitudinal cohort study using the DISC-IV as the gold standard for diagnosing depression. PHQ-9 and PHQ-2 sensitivity and specificity were calculated. ROC curves were constructed for the overall sample and YAPHIV and YAPHEU subsamples. Almost all participants were Black and Latinx, ages 18-29. Overall, the recommended PHQ-9 cut-score of ≥10 yielded a sensitivity of 0.47 (95%CI [0.23,0.72]) and specificity of 0.86 (95%CI [0.80, 0.91]). Results indicate that PHQ-9 cut-scores of 7 and PHQ-2 cut-scores of 2 increased sensitivity to 0.76 (95%CI [0.50, 0.93]) and 0.71(95%CI [0.44,0.90]), and decreased specificity to 0.72 (95%CI [0.65, 0.79]) and 0.73 (95%CI [0.66, 0.79]) respectively. Among subsamples, existing PHQ-9 cut-scores were more accurate for MDD diagnoses in YAPHEU (N = 11) than YAPHIV(N = 6). No race/ethnicity or age differences were found. Participants were recruited from clinics in NYC and may not reflect all YAPHIV and YAPHEU. Without a white HIV comparison group, no conclusions could be made on the impact of race/ethnicity on optimized PHQ-9 cut-scores. Using tailored cut scores for HIV-affected populations may increase identification of those experiencing or at risk for MDD. Given the need for increased depression screening in HIV care, use of optimized cut-scores could benefit at-risk populations in the US and globally.


EPR dosimetric properties of radiation--formed radicals in arginine monohydrochloride.
Arginine monohydrochloride rods (3×10 mm) were irradiated with (60)Co γ-rays to study radicals for dosimetric materials with Electron Paramagnetic Resonance (EPR). The rods have significant signal which develops upon irradiation and the intensity of signal increases upon the increase in irradiation dose. The rods can be used in the dose range from 5 to 120 KGy. The temperature coefficient was found to equal +0.22% °C(-1). The dose response, influence of humidity and post-irradiation storage at different conditions are discussed. The overall uncertainty for calibration of arginine monohydrochloride rode dosimeters at 2σ was found to be 2.85%.


Evaluation of the Weibull and log normal distribution functions as survival models of Escherichia coli under isothermal and non isothermal conditions.
Published survival curves of Escherichia coli in two growth media, with and without the presence of salt, at various temperatures and in a Greek eggplant salad having various levels of essential oil, all had a characteristic downward concavity when plotted on semi logarithmic coordinates. Some also exhibited what appeared as a 'shoulder' of considerable length. Regardless of whether a shoulder was noticed, the survival pattern could be considered as a manifestation of an underlying unimodal distribution of the cells' death times. Mathematically, the data could be described equally well by the Weibull and log normal distribution functions, which had similar modes, means, standard deviations and coefficients of skewness. When plotted in their probability density function (PDF) form, the curves also appeared very similar visually. This enabled us to quantify and compare the effect of temperature or essential oil concentration on the organism's survival in terms of these temporal distributions' characteristics. Increased lethality was generally expressed in a shorter mean and mode, a smaller standard deviation and increased overall symmetry as judged by the distributions' degree of skewness. The 'shoulder', as expected, simply indicated that the distribution's standard deviation was much smaller than its mode. Rate models based on the two distribution functions could be used to predict non isothermal survival patterns. They were derived on the assumption that the momentary inactivation rate is the isothermal rate at the momentary temperature at a time that corresponds to the momentary survival ratio. In this application, however, the Weibullian model with a fixed power was not only simpler and more convenient mathematically than the one based on the log normal distribution, but it also provided more accurate estimates of the dynamic inactivation patterns.


Impact of SDH Mutations in Alternaria solani on Recently Developed SDHI Fungicides Adepidyn and Solatenol.
Early blight, caused by Alternaria solani, is observed annually in all midwestern potato production areas. The use of foliar fungicides remains a primary management strategy. However, A. solani has developed reduced sensitivity or resistance to many single-site fungicides such as quinone outside inhibitor (QoI, FRAC group 11), succinate dehydrogenase inhibitor (SDHI, FRAC group 7), demethylation inhibitor (DMI, FRAC group 3), and anilinopyrimidine (AP, FRAC group 9) fungicides. Boscalid, fluopyram, solatenol, and adepidyn are EPA-registered SDHI fungicides used commercially on a variety of crops, including potato. Five SDH mutations have been characterized previously in A. solani that affect the efficacy of boscalid while only one of these mutations has been demonstrated to negatively affect fluopyram efficacy. Conidial germination assays were used to determine if a shift in sensitivity has occurred in these SDHI fungicides. A. solani isolates collected prior to the commercial application of SDHI fungicides (baseline) were compared with recently collected isolates (nonbaseline). Greenhouse evaluations were conducted also to evaluate the efficacy of boscalid, fluopyram, solatenol, and adepidyn on A. solani isolates possessing individual SDH mutations. Additionally, field trials were conducted to determine the effects of application of these SDHI fungicides on the frequency of SDH mutations. Fluopyram, solatenol, and adepidyn had high intrinsic activity against A. solani when compared with boscalid, based on in vitro assays. The application of adepidyn and solatenol resulted in greater early blight control than the application of boscalid and fluopyram in greenhouse experiments. Molecular characterization of A. solani isolates collected from the field trials determined that the frequency of the H134R-mutation can increase in response to more recently developed SDHI fungicides. In contrast, the H278R/Y- and H133R-mutations decreased to the point of being nearly absent in these field experiments.


The inversion effect on gaze perception reflects processing of component information.
When faces are turned upside-down they are much more difficult to recognize than other objects. This "face inversion effect" has often been explained in terms of configural processing, which is impaired when faces are rotated away from the upright. Here we report a "gaze inversion effect" and discuss whether it is related to configural face processing of the whole face. Observers reported the gaze locations of photographed upright or inverted faces. When whole faces were presented, we found an inversion effect both for constant errors and observer sensitivity. These results were closely replicated when only the eyes were visible. Together, our findings suggest that gaze processing is largely based on component-based information from the eye region. Processing this information is orientation-sensitive and does not seem to rely on configural processing of the whole face.


Resting state functional connectivity in the default mode network: Relationships between cannabis use, gender, and cognition in adolescents and young adults.
Cannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults; results are somewhat inconsistent across studies, potentially due to methodological differences. The aims of the present study were to examine potential differences in DMN RSFC between cannabis users and controls, and to examine, as an exploratory analysis, if gender moderated any findings. We further examined whether differences in RSFC related to differences in performance on selected neuropsychological measures. Seventy-seven 16-26-year-old participants underwent an MRI scan (including resting state scan), neuropsychological battery, toxicology screening, and drug use interview. Differences in DMN connectivity were examined between groups (cannabis vs. control) and with an exploratory group by gender interaction, using a left posterior cingulate cortex (PCC) seed-based analysis conducted in AFNI. Cannabis users demonstrated weaker connectivity than controls between the left PCC and various DMN nodes, and the right Rolandic operculum/Heschl's gyrus. Cannabis users demonstrated stronger connectivity between the left PCC and the cerebellum and left supramarginal gyrus. The group by gender interaction was not significantly associated with connectivity differences. Stronger left PCC-cerebellum connectivity was associated with poorer performance on cognitive measures in cannabis users. In controls, intra-DMN connectivity was positively correlated with performance on a speeded selective/sustained attention measure. Consistent with our hypotheses and other studies, cannabis users demonstrated weaker connectivity between the left PCC and DMN nodes. Chronic THC exposure may alter GABA and glutamate concentrations, which may alter brain communication. Future studies should be conducted with a larger sample size and examine gender differences and the mechanism by which these differences may arise.


The dendritic cell lineage: a ubiquitous antigen-presenting organization.
Dendritic cells are specialized antigen-presenting cells with two unique characteristics: the greatest stimulatory potential and the ability to stimulate naive T-lymphocytes. They originate from the bone marrow and reach their destination via hematogenous or lymphatic migration. Their phenotype is characterized by a high expression of major histocompatibility complex class II molecules and a high expression of adhesion molecules (CD25, CD54, CD58, CD72, and CD80). Pulmonary dendritic cells may be investigated by histologic examination, phenotype analysis, and function studies in a mixed lymphocyte reaction. Their isolation requires enzymatic digestion of lung tissue and subsequent steps of cell separation. The complexity of these manipulations makes it difficult to obtain large numbers of viable cells. A close anatomic relationship with alveolar macrophages underlines a functional interconnection: macrophages down-regulate the antigen-presenting function through release of tumor necrosis factor alpha. Dendritic cells most probably play a major role in lung diseases such as histiocytosis, primary and secondary cancers, and both acute and chronic lung graft rejection. Identification of the precise functional pathways might lead to therapeutic use of modulation of dendritic cell function.


Incidence and significance of opportunistic fungi in leukemia patients in India.
Twenty-four patients with acute leukemia were investigated for the incidence of opportunistic fungi. Culture isolations of the sputum and urine samples revealed significant levels of Candida in 14 patients; Candida albicans, C. tropicalis and C. pseudotropicalis were the predominant ones isolated. Aspergillus flavus was isolated from blood in two cases and C. albicans and a black yeast from the blood of another two. Serological studies showed fungal antibodies in seven patients; precipitins against Candida were detected in five and Aspergillus in two. Both of the Aspergillus positive cases and two patients who had rising antibodies against Candida died during the course of investigation. In this study 13 of 24 patients developed oral candidiasis.


Central corneal thickness in patients with atopic keratoconjunctivitis.
The aim of this study was to evaluate central corneal thickness in patients with atopic keratoconjunctivitis. The study was conducted in the Atatürk University School of Medicine between April 2011 and June 2013. The study group included 60 eyes of 30 patients with atopic keratoconjunctivitis. Sixty eyes of 30 healthy individuals without any ophthalmic or systemic pathology were used as a control group. The central corneal thickness was measured with ultrasonic pachymetry. In each group, all subjects included in the study had a best corrected visual acuity (BCVA) of 20/25 or better. In the study group past medical histories revealed eczema in 19 patients, asthma in 16, and atopic dermatitis in 15. During clinical examination cicatricial conjunctivitis was noted in 5 patients, giant papillae in 4, symblepharon in 2, and entropion in 2. The mean central corneal thickness was 523.45±18.03 µm in the study group (mean age: 37.05±5.7 years) and 540.30±38.91 µm in the control group (mean age: 36.55±7.1 years), and the difference was statistically significant (p<0.001). Evaluation of corneal thickness is important in situations such as corneal refractive surgery and contact lens use, and is an essential parameter in a wide range of ocular disorders, including glaucoma and keratoconus. Therefore, ophthalmologists should be aware of the low central corneal thickness in patients with atopic keratoconjunctivitis.


Free prednisolone pharmacokinetics predicted from total concentrations in patients with inflammatory - immunonologic conditions.
Prednisone is an anti-inflammatory drug widely used in internal medicine and rheumatology, but dosing remains empirical. The active metabolite of prednisone is free prednisolone. The aim of this work was to build a population pharmacokinetic (PK) model that can predict free prednisolone concentrations in patients with inflammatory/immunologic conditions.A total of 107 patients from the department of internal medicine of Cochin hospital provided 343 observations. Blood samples drawn for biological analyses were used for drug determination. Total plasma prednisolone concentrations were measured by liquid chromatography-mass spectrometry, and the data were modelled using Monolix. The pharmacokinetics was ascribed a one-compartment open model with three transit compartments standing for the absorption and metabolism process. The model used predicts free concentrations that served to derive total concentrations given published binding constants. Only size parameters influenced the pharmacokinetics. Free prednisolone CLU /F and VU /F, scaled allometrically on lean body weight, were, respectively, 26.7 L/h and 94.3 L for 50 kg LBW. CLU /F interindividual variability was 0.20. The additive and proportional residual variabilities were, respectively, 4.3 µg/L and 0.20. The results point out some dosing issues, that is the possibility of under- or over-dosage in thin or overweight patients respectively.


Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.
Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.


High prevalence of large trematode eggs in schoolchildren in Cambodia.
Large trematode eggs (LTE) resembling Fasciola spp. eggs were reportedly found in the stools of schoolchildren in Kandal province, Cambodia. This study aimed to assess the prevalence of LTE in the stools of children attending the affected school, identify potential risk factors for infection and ascertain the trematode species. We performed a cross-sectional study involving an in-depth questionnaire administered to schoolchildren at the affected school, and examined cattle droppings in the surrounding area and the livers of slaughtered cattle. Three stool samples were examined per child, using Kato-Katz and formalin-ether concentration techniques. In addition, blood serum enzyme-linked immunosorbent assay (ELISA) and coprological polymerase chain reaction (PCR) was conducted for species clarification. Cattle droppings were examined by cup sedimentation and coprological ELISA. LTE were observed in the stools of 106 schoolchildren (46.5%). Two blood serum samples from schoolchildren were positive for Fasciola hepatica in a first ELISA but were negative in a confirmation immunofluorescence antibody test. Out of 221 PCR samples, only one tested positive for Fasciola spp. and none for Fasciolopsis buski. The consumption of raw aquatic plants (odds ratio (OR)=3.3) and fermented fish sauce (OR=2.1) were significantly associated with LTE in the stool. Fasciola spp. flukes were observed in 18.3% of 191 cattle livers. The prevalence of fascioliasis in cattle droppings was 88.8%. The low prevalence of schoolchildren that tested positive for Fasciola spp. with specific molecular diagnostics and who had no diagnostic evidence of F. buski strongly indicates that the majority of microscopically observed LTE are from Echinostoma spp. Fasciola spp. transmission from cattle to human is possible and public health services need to be alerted accordingly.


A new pedicled seromuscular flap technique for high-risk intestinal anastomoses.
A new method for protecting intestinal anastomoses in patients at high risk of anastomotic dehiscence or fistula formation is described herein. This method involves raising a seromuscular flap on a pedicle from the stump of the intestine to be anastomosed. The anastomosis is performed, then covered with the seromuscular flap.


Cell biological and physicochemical aspects of arterial calcification.
Processes similar to endochondral or intramembranous bone formation occur in the vascular wall. Bone and cartilage tissue as well as osteoblast- and chondrocyte-like cells are present in calcified arteries. As in bone formation, apoptosis and matrix vesicles play an important role in the initiation of vascular calcification. Recent evidence indicates that nanocrystals initially formed in the vessel wall may actively be involved in the progression of the calcification process. This review focuses on the cellular and structural similarities between bone formation and vascular calcification and discusses the initial events in this pathological mineralization process.


Efficient CRISPR/Cas9 mutagenesis for neurobehavioral screening in adult zebrafish.
Adult zebrafish are widely used to interrogate mechanisms of disease development and tissue regeneration. Yet, the prospect of large-scale genetics in adult zebrafish has traditionally faced a host of biological and technical challenges, including inaccessibility of adult tissues to high-throughput phenotyping and the spatial and technical demands of adult husbandry. Here, we describe an experimental pipeline that combines high-efficiency CRISPR/Cas9 mutagenesis with functional phenotypic screening to identify genes required for spinal cord repair in adult zebrafish. Using CRISPR/Cas9 dual-guide ribonucleic proteins, we show selective and combinatorial mutagenesis of 17 genes at 28 target sites with efficiencies exceeding 85% in adult F0 "crispants". We find that capillary electrophoresis is a reliable method to measure indel frequencies. Using a quantifiable behavioral assay, we identify seven single- or duplicate-gene crispants with reduced functional recovery after spinal cord injury. To rule out off-target effects, we generate germline mutations that recapitulate the crispant regeneration phenotypes. This study provides a platform that combines high-efficiency somatic mutagenesis with a functional phenotypic readout to perform medium- to large-scale genetic studies in adult zebrafish.


Metabolic engineering of Paenibacillus polymyxa for effective production of 2,3-butanediol from poplar hydrolysate.
2,3-Butanediol is an essential renewable fuel. The synthesis of 2,3-butanediol using Paenibacillus polymyxa has attracted increasing attention. In this study, the glucose-derived 2,3-butanediol pathway and its related genes were identified in P. polymyxa using combined transcriptome and metabolome analyses. The functions of two distinct genes ldh1 and ldh3 encoding lactate dehydrogenase, the gene bdh encoding butanediol dehydrogenase, and the spore-forming genes spo0A and spoIIE were studied and directly knocked out or overexpressed in the genome sequence to improve the production of 2,3-butanediol. A raw hydrolysate of poplar wood containing 27 g/L glucose and 15 g/L xylose was used to produce 2,3-butanediol with a maximum yield of 0.465 g/g and 93 % of the maximum theoretical value, and the total production of 2,3-butanediol and ethanol reached 21.7 g/L. This study provides a new scheme for engineered P. polymyxa to produce renewable fuels using raw poplar wood hydrolysates.


Direct visual inspection for cervical cancer screening: an analysis of factors influencing test performance.
The authors evaluated direct visual inspection of the cervix after the application of 5% acetic acid (DVI) as a cervical cancer screening test for use in low-resource settings. Four tests were used to screen 2754 previously unscreened women: DVI with and without x4.5 magnification and differentiating between all lesions and well-circumscribed lesions; testing for high-risk types of human papillomavirus DNA using the Hybrid Capture II assay, cervical cytology, and Cervicography. Women with positive results on any of the four screening tests were referred for colposcopy and histologic sampling. All women were tested for N. gonorrhea, C. trachomatis, T. vaginalis, and human immunodeficiency virus 1. Histologically confirmed carcinoma was diagnosed in 21 women (0.8%), high-grade squamous intraepithelial lesions (SILs) were diagnosed in 96 women (3.5%), and low-grade SILs were diagnosed in 102 women (3.7%). The estimated sensitivity of DVI when performed without magnification for high-grade SILs was 70%, with an estimated specificity of 79%. Magnification did not significantly improve sensitivity for high-grade SILs (74% with magnification) but significantly reduced specificity (77%). Restricting the definition of a positive DVI test to a well-defined acetowhite lesion reduced sensitivity and significantly improved specificity. Infection with T. vaginalis, N. gonorrhea, and C. trachomatis did not alter sensitivity or specificity. This study confirmed the utility of DVI as a primary screening test. Evaluation of the clinical effectiveness of screening with this low-cost and simple test in low-resource settings is necessary.


Network analysis of intra-hospital transfers and hospital onset clostridium difficile infection.
To explore how social network analysis (SNA) can be used to analyse intra-hospital patient networks of individuals with a hospital acquired infection (HAI) for further analysis in a geographical information systems (GIS) environment. A case and control study design was used to select 2008 patients. We retrieved locational data for the patients, which was then translated into a network with the SNA software and then GIS software. Overall metrics were calculated for the SNA based on three datasets and further analysed with a GIS. The SNA analysis compared cases to control indicating significant differences in the overall structure of the networks. A GIS visual representation of these metrics was developed, showing spatial variation across the example hospital floor. This study confirmed the importance that intra-hospital patient networks play in the transmission of HAIs, highlighting opportunities for interventions utilising these data. Due to spatial variation differences, further research is necessary to confirm this is not a localised phenomenon, but instead a common situation occurring within many hospitals. Utilising SNA and GIS analysis in conjunction with one another provided a data-rich environment in which the risk inherent in intra-hospital transfer networks was quantified, visualised and interpreted for potential interventions.


Risk of bias assessments in systematic reviews and meta-analyses of behavioral interventions for substance use outcomes.
This study aims to explore the current practice of risk of bias assessment in systematic reviews of behavioral clinical trials published in substance use journals and how assessment results were incorporated into meta-analysis. The authors searched for systematic reviews and meta-analyses of behavioral interventions published from 2016 to 2020 in 40 substance use journals. Two authors independently screened and extracted relevant information from each review. Different tools for risk of bias assessment and approaches of incorporating the risk of bias assessment results into meta-analysis were summarized. The study identified 35 systematic reviews and meta-analyses of behavioral clinical trials. Among the 35 reviews, 31 (89%) assessed the risk of bias of their included studies. Twelve (39%) of the 31 reviews incorporated these assessment findings into their meta-analysis of intervention effects (e.g., conducted meta-regression or subgroup analysis, sensitivity analysis, limited the synthesis only to the "high quality" studies). Performing and reporting risk of bias assessment remain inconsistent in published systematic reviews. Future systematic reviews and meta-analyses are encouraged to connect their risk of bias assessment findings with meta-analysis and follow the most updated PRISMA guidelines in reporting the methods and results of risk of bias assessment.


Effects of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial.
Current markers of iron deficiency (ID), such as ferritin and hemoglobin, have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n = 39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared with altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an antidoping context.


Surgical approach to pituitary tumors.
Pituitary surgery is a continuously evolving specialty of neurosurgery that requires precise anatomical knowledge, technical skills, and an integrated appreciation of pituitary pathophysiology. It involves close cooperation between different specialists, i.e., the endocrinologist, neurosurgeon, neuroradiologist, pathologist, ophthalmologist, and others. It is currently possible to manage many of the different pituitary syndromes with more than one option, including medical, surgical, and radiotherapeutic options, either alone or in various combinations. In recent decades, the transsphenoidal midline route became the standard approach to the pituitary area, this being a less traumatic direct route to the sella, avoiding brain retraction and providing excellent visualization, with a lower morbidity and mortality rate as compared to transcranial procedures. Most pituitary adenomas can be managed and removed through a standard transsphenoidal approach, either microscopic or endoscopic. More recently, the introduction of the endoscope in the extended endoscopic endonasal approach has become more widespread. Here we report current indications and give a step-by-step account of the surgical techniques used in pituitary surgery, focusing on the "dangerous keypoints". We also describe possible complications of each kind of procedure.


Mechanism of actin polymerization by myosin subfragment-1 probed by dynamic light scattering.
Monomeric actin (G-actin) polymerizes spontaneously into helical filaments in the presence of inorganic salts. The slowest, rate-limiting step of the polymerization process is formation of actin trimers, the smallest oligomers that serve as nuclei for fast filament growth (filament elongation) by monomer addition at the filament ends. In low ionic-strength solutions, actin can be polymerized by myosin subfragment-1 (S1). In early works it has been suggested that G-actin-S1 1:1 complexes (GS) assemble into filaments according to the nucleation-filament elongation scheme. Subsequent studies indicated that one S1 molecule can bind two actin monomers, and that oligomerization of the initial complexes is a fast reaction. This has led to suggest an alternative mechanism, with a ternary G(2)S complex and its oligomers being predominant intermediates of S1-induced assembly of G-actin into filaments. We used dynamic light scattering to analyze the initial steps of S1-induced polymerization of actin. Our results suggest formation of GS complexes and their oligomers in the presence of S1 equimolar to or in excess over actin. We confirm formation of G(2)S complexes as intermediates of S1-induced polymerization in the presence of actin in excess over S1.


The IUGA/ICS classification of complications of prosthesis and graft insertion: a comparative experience in incontinence and prolapse surgery.
This is a presentation of case series after the use of alloplasic material in urogynaecology. From 2004 to 2010, a total 179 patients with complications have been referred directly after the use of alloplastic material in incontinence and prolapse surgery. Of this total, 125 patients had a previous vaginal sling plasty because of urinary stress incontinence, while 54 patients underwent a prolapse surgery with mesh use. Symptoms and findings are expressed by the recently introduced International Urogynecological Association/International Continence Society (IUGA/ICS) terminology. The most frequent findings after vaginal sling plasty were bladder outlet obstruction, pain and tape exposure. The most frequent findings after prolapse surgery were pain and mesh erosion. The IUGA/ICS classification does not give the possibility to express functional disorders. Most revisions were done more than 2 months after surgery. After incontinence surgery, mostly the vaginal area of suture line was affected; after prolapse surgery, the vagina and the trocar passage were affected. Mesh complication and affected site after prolapse surgery do differ from those after incontinence surgery. The IUGA/ICS classification of mesh complication facilitates the comparison of mesh complication.


[Prevention of stress-induced changes in coronary autoregulation of vasodilative reserve of the coronary vessels and contractile function of the isolated heart with small doses of thyroid hormones].
The possibility to restrict stress disturbances of coronary blood flow and contractile myocardium function with small doses of thyroid hormones has been studied on 46 hearts of female rats isolated by the Langendorff method. It is found that small doses of thyroidin increase the force of systoles and adequately increase relative coronary blood flow, coronary reserve vasodilatation, significantly prevent stress disturbances of coronary autoregulation, the force and rate of the myocardium contraction and relaxation, that restricts disproportion between contractive function and coronary blood flow.


Subretinal fibrosis and uveitis syndrome associated with ulcerative colitis.
We report a case of subretinal fibrosis and panuveitis syndrome as an extraintestinal manifestation of ulcerative colitis. We present an interventional case report of a 40-year-old female patient with inactive ulcerative colitis referred to our center for refractory uveitis in her right eye. She was diagnosed with subretinal fibrosis and uveitis syndrome after work-up ruled out tuberculosis, bartonellosis, Lyme disease, and sarcoidosis. Right eye multifocal choroiditis and panuveitis syndrome with subretinal fibrosis was diagnosed, and posterior pole subretinal fibrosis caused a 90% loss of visual efficiency. She had concurrent dermatological manifestations but no gastrointestinal symptoms. One year of immunosuppressive therapy with methotrexate (7.5 mg/week) controlled ocular inflammation. Two colitis episodes, with no visual involvement, were recorded during follow-up. Her final, right-eye, best-corrected visual acuity remained stable at 0.160 due to scarring sequela after 7 years of follow-up. Subretinal fibrosis and uveitis syndrome can occur as a sight-threatening extraintestinal manifestation of ulcerative colitis.


Pretreatment depressive symptoms and treatment modality predict post-treatment disease-specific quality of life among patients with localized prostate cancer.
This study examines the prevalence of depressive symptoms before prostate cancer treatment and explores associations among pre-treatment depressive symptoms and post-treatment disease-specific QOL, controlling for treatment modality, and demographic and clinical covariates. A case series of patients diagnosed with localized prostate cancer (T1-2N0M0) at a comprehensive cancer center was assessed. Of the 1,370 eligible patients, 869 (63.34%) completed questionnaires at diagnosis (baseline) and 6 months following treatment. Patients were treated with surgery (16.8%), brachytherapy (27.6%), or external beam radiation (EBRT; 55.6%). Depressive symptoms and disease-specific QOL were assessed with established measures (i.e., Center for Epidemiologic Studies Depression Scale (CES-D); sexual adjustment questionnaire (SAQ); and the American Urological Association symptom index). A fifth of the sample (19.7%) reported clinically elevated levels of depressive symptoms at baseline. The proportion of clinically elevated levels of baseline depressive symptoms was higher among surgery patients compared with patients treated with brachytherapy or external beam radiation. Depressive symptoms at baseline and treatment modality significantly predicted sexual and urinary dysfunction, related bother, activity limitation due to urinary dysfunction at 6 months, controlling for, age, PSA level, Gleason score, relevant baseline indicators of sexual and urinary dysfunction, related bother, and activity limitation (P < 0.05). Pretreatment depressive symptoms and treatment modality predict QOL after PrCa treatment. Health care providers should be sensitive to the display of depressive symptoms before PrCa treatment and consider preventative interventions, including preparing patients for the changes in disease-specific QOL and related bother following prostate cancer treatment.


[ArtRoCad: health resources utilization and socioeconomic impact of knee and hip osteoarthritis. I. Methods and population characteristics].
The ArtRoCad study analyzes healthcare resource utilization and the socioeconomic impact of knee and hip osteoarthritis in primary care in Spain. The present study describes the methodology of the ArtRoCad study and presents the main characteristics of the population included. We performed a cross-sectional study of ambulatory patients in primary care, aged ≥ 50 years old, with a diagnosis of knee or hip osteoarthritis and a history of pain for 3 months in the previous year. The patients were selected consecutively on a country-wide basis, proportional to the general population aged ≥ 50 years. The most important localization for healthcare demand was considered the main affected joint. The study was performed in October and November, 2003. Information on clinical data, quality of life and resource consumption, sick leave from work or days of disability in the previous 6 months were gathered through 2 structured interviews. Eighty-seven percent of the physicians predicted by sampling participated in the study, accounting for 82% of the predetermined sample size. A total of 1,071 patients were interviewed. The distribution of the main affected joint was as follows: knee 710 (66.3%), hip 252 (23.5%) and both knee and hip 109 (10.2%). Seventy-five percent of the sample was aged 65 years or older and 74% were women. Most of the patients had moderate or severe osteoarthritis with a median pain duration of between 6 and 10 years. More than half the patients experienced additional limitations due to musculoskeletal problems other than knee and/or hip osteoarthritis. Participation in the ArtRoCad study was excellent. The sample obtained was representative of the population with symptomatic moderate or severe osteoarthritis of the knee and hip in primary care, with substantial comorbidity.


Enhanced suppression of pulmonary metastasis of malignant melanoma cells by combined administration of alpha-galactosylceramide and interleukin-18.
alpha-Galactosylceramide (alpha-GalCer) shows antitumor effects by activating natural killer (NK) cells indirectly through stimulation of the secretion of cytokines by NKT cells, whereas interleukin (IL)-18 shows antitumor effects by activating NK cells directly. In the present study, we examined the antitumor effect of the combined administration of alpha-GalCer and IL-18. An injection of NK cell-sensitive mouse B16 melanoma cells into a mouse tail vein produced pulmonary metastasis. The daily administration of alpha-GalCer or IL-18 alone for 4 days starting 1 day after the injection of B16 melanoma cells markedly suppressed the number of pulmonary metastatic foci, and their combined administration enhanced the antitumor effect compared with single administration. The antitumor effect of their combined administration was completely abolished by treatment of mice with anti-asialo GM1 serum, which depletes NK cells but not NKT cells. Combined administration of alpha-GalCer and IL-18 enhanced the cytotoxicity of NK cells and increased the number of NK cells in the lung. Analysis of NKT cell-dependent and NK cell-independent secretion of cytokines, to which NK cells can respond, showed that the administration of alpha-GalCer increased the secretion of IL-2, IL-4, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IL-10, and the combined administration of alpha-GalCer and IL-18 enhanced the secretion of IL-2, IL-4, interferon-gamma, and granulocyte-macrophage colony-stimulating factor further but only slightly. These results show that IL-18 in combination with alpha-GalCer exerts an antitumor effect on NK cell-sensitive tumors primarily by the direct stimulation of NK cells by IL-18 and the indirect stimulation of NK cells by alpha-GalCer through its activation of NKT cells.


Comments from the Editors on the Special Issue "Assessment and Treatment of Addictions: New Tools for Old Problems".
New conceptual and technological solutions have been proposed to solve addictive disorders and will be presented in the future. In this Special Issue, we present some of the new assessment tools and treatment options for internet addiction, alcohol, cannabis, cocaine, and gambling disorders.


Free-floating thrombus of the aorta: 3 case reports.
Idiopathic free-floating thrombus (FFT) of the aorta is a rare occurrence, but it can lead to catastrophic consequences. The initial symptoms are typically cerebral or peripheral embolisms. Surgical thrombectomy and thrombolysis are two primary treatments for FFT. Here, we report three cases of patients with idiopathic FFT in the absence of coagulopathy who were treated successfully by surgery with no recurrent thrombi or relapse of symptoms. Case 1 involved a 72-year-old male patient with a pedunculated thrombus in the distal aortic arch. Case 2 involved a 62-year-old female patient with a cylinder thrombus in the aortic arch and left common carotid artery. Case 3 involved a 65-year-old male patient with three pedunculated thrombi in the ascending aorta, aortic arch, and left subclavian artery. None of the patients had clinical signs of coagulopathy. Pedunculated or cylinder thrombi have a greater risk of breaking off, which can produce severe peripheral embolism in contrast with intramural thrombi (73% vs. 12%). Due to the high embolism risk for each patient, conservative medical treatment by heparinization was deemed inappropriate, so each patient underwent emergency surgical thrombus removal. After surgery, each of the three patients was treated with warfarin for secondary prevention of thromboembolism. At 7-month follow-up in outpatient practice, a computed tomography (CT) scan indicated that Patient 1 had no recurrent thrombus, and the patient has been symptom-free for 11 months. At 1-month follow-up in outpatient practice, a CT scan indicated that Patient 2 had no recurrent thrombus, and the patient has been symptom-free for 8 years. At 3-week follow-up in hospital, a CT scan indicated that Patient 3 had no recurrent thrombus, but he failed to follow-up after discharge, so his follow-up status is unknown. For a large pedunculated or cylinder thrombus located in the thoracic aorta, surgical thrombectomy should be performed. And, in surgical thrombectomy, the location of the cannulas and cross-clamp should be selected carefully according to the location of the thrombus. After surgery, anticoagulant is important to prevent recurrent idiopathic thrombi.


Epigenetics and senescence: learning from the INK4-ARF locus.
Cellular senescence is the biological consequence of aging. However, the same mechanisms that provoke senescence during aging have been proven to act in tumor suppression and thus to occur in premalignant cells. All the diverse aspects of the senescent phenotype, as are observed for many other cell fates, arise from alterations of the chromatin architecture. Relatively little is known overall about the changes in chromatin structure, and which regulatory networks are implicated in these. Major insight into the epigenetic contributions to senescence has been gained by studying the regulation of the INK4-ARF locus. Activation of the tumor suppressors encoded by this locus leads to an irreversible cell cycle exit. Importantly, epigenetic alterations at this locus have been associated with the onset of cancer. Here we discuss the recent findings that link epigenetics to the senescence pathway.


Research on the Influence of the Type of Surfactant and Concentrator in Aqueous Dispersion of Pigments.
This work reports tests performed to evaluate the stability of aqueous dispersions of inorganic oxide pigments with different specific surface areas, with the use of anionic and non-ionic surfactants and concentrators. Color mixtures of oxide compounds of blue, green, olive and brown with the unit cell spinel structure were used as pigments. The sodium salt of sulfosuccinic acid monoester, oxyethylenated nonylphenol and ethoxylated derivatives of lauryl alcohol, fatty alcohol and fatty amine were used as surfactants. The concentrators used were: poly(vinyl alcohol), the sodium salt of carboxymethyl cellulose as well as a water-based polyurethane oligomer. The highest dispersion efficiency was found for dispersed systems in which surfactant and concentrator were incorporated in the formula. The one containing the sodium salt of carboxymethyl cellulose or polyurethane oligomer with ethoxylated saturated fatty alcohol or fatty amine was found to be the most efficient. It was discovered that a higher dispersion efficiency corresponds to pigments with larger specific surface. The efficiency is also found to improve when the concentrator is an acrylic polymer or copolymer made up of two acrylic species. In this case, the concentrator interaction with the surfactant is more effective if the value of its boundary viscosity number is higher. This observation confirms the existence of interactions between macro-chains of the concentrator and surfactant molecules forming micelles with the pigment particles.


Catalysis design for ring-opening polymerization of cyclic esters: 1. Group 1 metal and thallium(I) trispyrazolylborate complexes with hemilabile ligands.
The synthesis of 3-(2-methoxy-1,1-dimethylethyl)pyrazole, pz*H is described together with its reactions with the borohydrides MBH(4), where M = Li, Na, and K, under melt conditions. At 180 degrees C, this procedure leads to a mixture of products for M = Li, and at higher temperatures, a derivative LiTp'pz*H, 1, is isolated, wherein a B-H bond and a methyl group have been eliminated and a B-O bond has been formed. For M = Na, the reaction proceeds to give the tris-pyrazolylborate derivative NaTp*, 2, but at higher temperatures the tetra-pyrazolylborate complex NaB(pz*)(4), 3, is obtained. The reactions involving KBH4 and pz*H yield the dinuclear complex K(2)(Tp*)(2)pz*H, 4. The reaction between NaTp* and TlOAc in CH(2)Cl(2) at room temperature leads to the formation of TlTp*, 5, along with NaOAc. Thallium 5 reacts with methyllithium in diethylether to give LiTp*, 6, and thallium metal, and, similarly, 5 and KH react in tetrahydrofuran to give KTp*, 7 and Tl(0). 1-7 have been characterized by elemental analysis, NMR spectroscopy, and by single-crystal X-ray studies, the latter of which reveal the versatile modes of binding for this new ligand bearing hemilabile ether appendages.


Cognitive-behavioral approaches to children's problems.
Selected issues in theory, research, methodology, assessment, and outcome are briefly discussed in the context of cognitive-behavioral approaches to children's problems. Distinctions between rationalistic and developmental varieties of cognitive approaches are delineated. Different assumptions are explored regarding the function and nature of cognitive processes, the nature and mechanisms of psychological change, and the relationship between cognitive and emotional processes. It is concluded that the empirical status of cognitive-behavioral approaches to children's problems is equivocal. The theoretical status of traditional (rationalistic) cognitive treatments is also challenged, and developmental, process-oriented conceptualizations and research are endorsed as more adequate and promising perspectives in this area.


Relationships between structure and biological activity of the mycolic acid-containing glycolipids from Nocardia asteroides "sensu stricto" and related species.
To reveal the taxonomical situation of Nocardia asteroides "sensu stricto", we compared the mycolic acid and mycolic acid-containing glycolipid composition and their granulomagenic activities in mice. The major glycolipids were glucose mono- and dimycolate, trehalose mono- and dimycolate and several unknown glycolipids, commonly, although the relative amount differed from strain to strains. On the other hand, molecular species composition of mycolic acids differed distinctively among the three closely related species: N. asteroides "sensu strico", N. farcinica and N. nova. GC/MS analysis showed the most abundant species of mycolic acids were C50(52) in N. asteroides, C54(52) in N. farcinica and C58(56) in N. nova, respectively with a different alpha-alkyl branch. Glucose mycolate and trehalose dimycolate possessing C50 mycolic acid showed a strong activity for granuloma formation in mice.


Data on lateral collection length of charge carriers depending on pre-white-light soaking process for metal mesh transparent electrode based Cu(In,Ga)Se2 solar cells.
The authors have recently reported silver nanowire based Cu(In,Ga)Se2 solar cells [1,2]. Metal mesh based transparent electrodes other than the silver nanowire can be also employed or have a potential to provide a better performance for the solar cells. To select a suitable electrode for a solar cell among metal meshes, it is required to have data on the lateral collection length of charge carriers in the targeted cell. The method to determine the lateral collection has been reported in our previous publication [3]. Here, we report data on the effect of the light intensity during pre-white-light soaking on the lateral charge collection length for metal mesh transparent electrode based Cu(In,Ga)Se2 solar cells.


Cytokine storms caused by novel coronavirus 2019 and treatment for cardiac injury.
Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.


Hyaluronic acid/chitosan nanoparticles for delivery of curcuminoid and its in vitro evaluation in glioma cells.
The aim of this work was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan (HA/CS) as carriers for water-insoluble curcuminoid (CUR) and explore in vitro performance against brain glioma cells. PENPs were observed to be affected by the order of addition, mass ratios and initial concentrations of the HA/CS, pH and ionic strength. PENPs remained stable over a temperature range of 5–-55(C. CUR was successfully encapsulated into the PENPs. CUR-PENPs showed spherical shape with a mean diameter of 207 nm and positive charge of 25.37 mV. High encapsulation efficiency (89.9%) and drug loading (6.5%) was achieved. Drug release studies revealed initial burst release of drug from the PENPs up to 4h followed by sustained release pattern. DSC thermograms and XRD patterns showed that CUR was encapsulated inside the PENPs in a molecular or amorphous state. Compared with CUR-solution, CUR-PENPs showed stronger dose dependent cytotoxicity against C6 glioma cells and higher performance in uptake efficiency in C6 cells. Cellular uptake of CUR-PENPs was found to be governed by multi-mechanism in C6 cells, involving active endocytosis, macropinocytosis, clathrin-, caveolae-, and CD44-mediated endocytosis. In conclusion, CUR-PENPs might be a promising carrier for therapy of brain gliomas.


Erratum regarding missing Declaration of Competing Interest statements in previously published articles.
[This corrects the article DOI: 10.1016/j.jcte.2018.12.008.][This corrects the article DOI: 10.1016/j.jcte.2018.03.002.][This corrects the article DOI: 10.1016/j.jcte.2018.06.001.][This corrects the article DOI: 10.1016/j.jcte.2020.100224.][This corrects the article DOI: 10.1016/j.jcte.2019.100187.][This corrects the article DOI: 10.1016/j.jcte.2019.100202.][This corrects the article DOI: 10.1016/j.jcte.2019.100195.][This corrects the article DOI: 10.1016/j.jcte.2020.100222.][This corrects the article DOI: 10.1016/j.jcte.2020.100230.][This corrects the article DOI: 10.1016/j.jcte.2018.09.001.].


Longitudinal study of smoking cessation before pregnancy and children's cognitive abilities at 56 months of age.
An inverse relationship exists between the rates of maternal smoking during pregnancy and children's cognitive abilities. The effect of maternal cessation of smoking before pregnancy on child's cognitive development is less clear. To study whether maternal cessation of smoking before pregnancy is associated with children's cognitive abilities. The original cohort included all 1535 live-born infants admitted to the neonatal wards during 1 year and 658 randomly recruited non-admitted infants. The present study sample comprised 1019 (68.2%) children of the original sample born at term and free of any major impairment followed up to 56 months. Child's general reasoning, visual-motor integration, verbal competence, and language comprehension at 56 months of age. The results showed that children whose mothers smoked >10 cigarettes per day before pregnancy but none during pregnancy, fared 12.07 (95% confidence interval [CI]: 4.07 to 20.08) and 11.23 (95% CI: 2.81 to 19.66) age-standardized points poorer in general reasoning and in language comprehension tests, respectively, than children of never-smokers. All results were adjusted for the sex, gestational age-adjusted birth weight, multiple/singleton pregnancy, birth order, preeclampsia, maternal diabetes, admission to neonatal ward, 5-minute Apgar score (<7), breastfeeding, parental level of education, maternal age, BMI at the end of pregnancy and single parenting. Heavy smoking before pregnancy is associated with children's lower cognitive abilities even if the mother has quit smoking before pregnancy. Identification and intervention of heavy smoking women of fertile age would potentially improve not only their odds to become pregnant but also benefit the offspring's cognitive functioning.


Nano-engineered screen-printed electrodes: A dynamic tool for detection of viruses.
There is a growing interest in the development of portable, cost-effective, and easy-to-use biosensors for the rapid detection of diseases caused by infectious viruses: COVID-19 pandemic has highlighted the central role of diagnostics in response to global outbreaks. Among all the existing technologies, screen-printed electrodes (SPEs) represent a valuable technology for the detection of various viral pathogens. During the last five years, various nanomaterials have been utilized to modify SPEs to achieve convincing effects on the analytical performances of portable SPE-based diagnostics. Herein we would like to provide the readers a comprehensive investigation about the recent combination of SPEs and various nanomaterials for detecting viral pathogens. Manufacturing methods and features advances are critically discussed in the context of early-stage detection of diseases caused by HIV-1, HBV, HCV, Zika, Dengue, and Sars-CoV-2. A detailed table is reported to easily guide readers toward the "right" choice depending on the virus of interest.


Ocular changes of non-segmental vitiligo: A case-control study.
Vitiligo is a skin disorder in which the melanocytes are destroyed. Melanocytes can be destroyed anywhere in the body, compromising the function of the organs where they are found. Melanocytes in the epidermis and the uveal tract share a common embryological origin in addition to physiological and morphological similarities. Our aim was to detect ocular changes in non-segmental vitiligo patients. This study included 40 non-segmental vitiligo patients and 40 healthy volunteers as a control. Visual acuity testing, slit lamp examination and optical coherence tomography were performed on all patients as well as controls. Patients with non-segmental vitiligo had a considerably greater incidence of ocular alterations than controls, although there was no significant difference in visual acuity. Vitiligo is a systemic condition that can affect the activity of melanocytes in organs besides the skin. The depigmentation process can influence ocular melanocytes. Ocular problems may be closely connected to vitiligo. Because ocular melanocytes aren't involved in the detection or transmission of visual pathway, there is no vision impairment.


[Quality of life for wearers of a suprapubic or transurethral bladder catheter as lifelong permanent care].
The insertion of a Foley catheter (FC) or a suprapubic catheter (SPC) in lifelong intent is an intervention with significant complications, comorbidities and impact on the further life that has not yet been analyzed. The analysis was based on a validated assessment of catheter-related QoL with 25 items in 5 domains and applied to patients with a Foley or suprapubic catheter in lifelong indication and with the catheter in place for at least 3 months. Assessment data were enriched with information on the type and diameter of the catheter as well as demographic data. Questionnaires from 357 patients (260 male, 97 female, 193 with suprapubic catheter, 162 with Foley catheter, 2 no information) were included in the study. Patients with a Foley catheter were significantly older than patients with a suprapubic catheter (78.9 ± 11.1 years vs. 74.4. ± 12.6 years, p < 0.001). The average QoL score was 4.1 points on a scale from 1 (maximum impairment of QoL) to 5 (no impairment of QoL) indicating a moderately negative impact on QoL. Scores below the average were mainly driven and accompanied by a fear of urine leakage, urine odor, painful catheter changes and urinary infections increasing with age. Additionally, patients were worried about negative effects on their daily life activities due to the catheter. These worries seemed to be more pronounced in females with urinary incontinence, patients with a catheter size ≥ 18 Ch. and with an age of < 70 years. The type of catheter showed a greater impact on the QoL in females with suprapubic catheters when compared with males in contrast to patients with transurethral catheters. The results of the study provide further information for the medical clarification for patients and caregivers, having to decide between a lifelong catheter drainage or alternatives, such as provision of an aid or surgical recanalization.


Thermography of frozen shoulder and rotator cuff tendinitis.
The role of thermography in the diagnosis of soft tissue lesions of the shoulder was evaluated by screening 28 patients with unilateral frozen shoulder and 86 patients with unilateral rotator cuff lesions. Index shoulders were then compared with the normal side. Differences in skin temperature distribution were found in 82% of subjects with frozen shoulder, nearly three-quarters of whom had reduced skin temperature. There was no consistent pattern of shoulder skin temperature found in rotator cuff tendinitis patients (49% normal, 28% reduced, 23% increased). Thermography can be helpful in the diagnosis of frozen shoulder but further studies are required to determine whether it is useful in other soft tissue shoulder lesions.


Variety of endosomal TLRs and Interferons (IFN-α, IFN-β, IFN-γ) expression profiles in patients with SLE, SSc and MCTD.
We investigated Toll-like receptor (TLR)-3/-7/-8/-9 and interferon (IFN)-α/β/γ mRNA expression in whole blood and serum IFN-α/β/γ levels in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and in healthy subjects to assess the association between the TLR-IFN expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN-γ, TLR-3 and TLR-8 was detected only in SLE patients. TLR-7, IFN-α and IFN-β expression was highest in SLE, while TLR-9 expression was highest in SSc patients. In SLE and MCTD patients a strong correlation was observed between TLR-7 and IFN-α expression and IFN-β and IFN-α expression. In MCTD patients, negative correlation between IFN-α and TLR-9 and TLR-7 and TLR-9 was revealed. TLR-9 expression in anti-U1-70k-negative, anti-C negative and anti-SmB-negative MCTD patients was higher than in MCTD-positive patients. We observed negative correlations between serum IFN-α levels and TLR-7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN-γ, TLR-3 and TLR-8 expression increased the value of C3 and C4. Our results confirmed that the endosomal TLR-IFN pathway seems to be more important in SLE than in MCTD or SSc, and that IFN-α and IFN-β may be possible biomarkers for SLE.


Study on controllable enzymolysis by chiral capillary electrophoresis with an ultraviolet-visible responsive polymer membrane based l-asparaginase reactor.
Stimuli-responsive polymer enzyme reactors have become a major area of research interest, from their fundamental aspects to applications in bio-living science. However, the polymer materials, that enable the controllable enzymolysis based on ultraviolet-visible (UV)-responsive properties, have remained unexplored. Herein, an enzyme reactor was fabricated by immobilization of l-asparaginase on an UV-responsive porous polymer membrane (UV-PPMER), which consisted of poly(styrene-maleicanhydride-4-[(4-methacryloyloxy)phenylazo]benzoic acid) [P(St-MAn-MPABA)], and explored its controllable enzymolysis. By controlling the "on/off" switch of 365 nm UV irradiation, the configuration of polymer membrane surface changed to improve and tune the enzymolysis. Using l-asparagine (L-Asn) as the substrate, the enzymatic efficiency of the UV-PPMER was evaluated by a chiral capillary electrophoresis technique. Upon UV irradiation, the PMPABA moiety in the membrane changed from a trans- to a cisconfiguration and encapsulated the enzyme and substrate into a narrow cavity, further improving the enzymatic efficiency due to the confinement effect. It was found that the enzymatic reaction rate with the UV-PPMER under UV irradiation (13.3 mM min-1) was 4.5 times higher than that of UV irradiation was off (2.94 mM min-1). Additionally, the low cytotoxicity and excellent UV-responsivity of UV-PPMER were verified in the living cells and serum samples.


[Research Advances on Transformation to Small Cell Lung Cancer].
The transformation of non-small cell lung cancer to small cell lung cancer (SCLC) is one of the major resistant mechanisms, especially patients with epidermal growth factor receptor mutant lung adenocarcinoma. Translational SCLC has been found to have similar clinical features to primary SCLC. Chemotherapy was short-term effective for transformational SCLC, with a median survival of only about 1 year. The deletion of RB1 and the change of somatic copy number were associated with SCLC transformation. Although the molecular mechanism of SCLC transformation is still not fully understood. At the same time, the treatment of transformational SCLC also faces great challenges. Currently, chemotherapy regimens for SCLC are the main treatment options for transforming SCLC. Combination therapy, local treatment and strategies for prevention of SCLC transformatio are also being explored. This article will review research advances on the clinical features, molecular mechanism and treatment options of translational SCLC. .


Effects of elevated CO2 on metabolic rate and nitrogenous waste handling in the early life stages of yellowfin tuna (Thunnus albacares).
Ocean acidification is predicted to have a wide range of impacts on fish, but there has been little focus on broad-ranging pelagic fish species. Early life stages of fish are thought to be particularly susceptible to CO2 exposure, since acid-base regulatory faculties may not be fully developed. We obtained yellowfin tuna (Thunnus albacares) from a captive spawning broodstock population and exposed them to control or 1900 μatm CO2 through the first three days of development as embryos transitioned into yolk sac larvae. Metabolic rate, yolk sac depletion, and oil globule depletion were measured to assess overall energy usage. To determine if CO2 altered protein catabolism, tissue nitrogen content and nitrogenous waste excretion were quantified. CO2 exposure did not significantly impact embryonic metabolic rate, yolk sac depletion, or oil globule depletion, however, there was a significant decrease in metabolic rate at the latest measured yolk sac larval stage (36 h post fertilization). CO2-exposure led to a significant increase in nitrogenous waste excretion in larvae, but there were no differences in nitrogen tissue accumulation. Nitrogenous waste accumulated in embryos as they developed but decreased after hatch, coinciding with a large increase in nitrogenous waste excretion and increased metabolic rate in newly hatched larvae. Our results provide insight into how yellowfin tuna are impacted by increases in CO2 in early development, but more research with higher levels of replication is needed to better understand long-term impacts and acid-base regulatory mechanisms in this important pelagic fish.


Prevention of invasive ventilation (PRiVENT)-a prospective, mixed-methods interventional, multicentre study with a parallel comparison group: study protocol.
Invasive mechanical ventilation (IMV) is a standard therapy for intensive care patients with respiratory failure. With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV increases, resulting in impaired quality of life and high costs. In addition, human resources are tied up in the care of these patients. The PRiVENT intervention is a prospective, mixed-methods interventional, multicentre study with a parallel comparison group selected from insurance claims data of the health insurer Allgemeine Ortskrankenkasse Baden-Württemberg (AOK-BW) conducted in Baden-Württemberg, Germany, over 24 months. Four weaning centres supervise 40 intensive care units (ICUs), that are responsible for patient recruitment. The primary outcome, successful weaning from IMV, will be evaluated using a mixed logistic regression model. Secondary outcomes will be evaluated using mixed regression models. The overall objective of the PRiVENT project is the evaluation of strategies to prevent long-term IMV. Additional objectives aim to improve weaning expertise in and cooperation with the adjacent Intensive Care Units. This study is registered at ClinicalTrials.gov (NCT05260853).


Dietary omega-6/omega-3 ratio is not associated with gut microbiota composition and disease severity in patients with nonalcoholic fatty liver disease.
In this cross-sectional study, we hypothesized that a high dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids could be associated with an altered gut bacterial composition and with the disease severity in patients with nonalcoholic fatty liver disease (NAFLD). A total of 101 NAFLD patients were included in the study, of which 63 underwent a liver biopsy. All 101 patients completed a 14-day food and activity record. Ebispro 2016 professional software was used to calculate individual macronutrients and micronutrients consumed. Patients were grouped into 3 quantiles (Q) according to a low (Q1: <6.1, n = 34), moderate (Q2: 6.1-7.8, n = 33), or high (Q3: >7.8, n = 34) dietary n-6/n-3 ratio. Stool samples were analyzed using 16S rRNA gene sequencing. Spearman correlation coefficients and principal coordinate analysis were used to detect differences in the bacterial composition of the gut microbiota. The median dietary n-6/n-3 ratio of all patients was 6.7 (range, 3.1-14.9). No significant associations between the dietary n-6/n-3 ratio and the gut microbiota composition or disease severity were observed. However, the abundance of specific bacteria such as Catenibacterium or Lactobacillus ruminis were found to be positively correlated and the abundance of Clostridium were negatively correlated with dietary n-6 fatty acid intake. The results indicate that a high dietary n-6/n-3 ratio is probably not a highly relevant factor in the pathogenesis of human NAFLD. Further studies are needed to clarify the importance of interactions between gut bacterial taxa and n-6 fatty acids in the pathophysiology of NAFLD.


Effects of a Simulation-Based CPR Training Program on Knowledge, Performance, and Stress in Clinical Nurses.
Rapid and accurate cardiopulmonary resuscitation (CPR) performed by clinical nurses plays an important role in increasing the survival rate of cardiac arrest patients in the hospital. This study examined the effects of a simulation-based CPR training program on knowledge, performance, and stress of CPR in clinical nurses. A quasi-experimental pretest-posttest control group design was used. Study participants included 60 clinical nurses (experimental group, n = 30, and control group, n = 30) in a general hospital in Seoul, South Korea. A 4-hour simulation-based CPR training program was conducted. Measures included the knowledge scale and performance scale from the Korean Association of Cardiopulmonary Resuscitation and the Post Code Stress Scale in Korean. The simulation-based CPR training program significantly improved CPR knowledge (t = 4.664, p < .001) and performance (t = 4.940, p < .001), and decreased stress (t = -5.832, p < .001) in clinical nurses. These findings indicate a simulation-based CPR training program was effective in improving knowledge and performing CPR, as well as in decreasing stress of CPR in clinical nurses. [J Contin Educ Nurs. 2020;51(5):225-232.].


Purification and properties of an extremely thermostable NADP+-specific glutamate dehydrogenase from Archaeoglobus fulgidus.
NADP+-specific glutamate dehydrogenase (EC 188.8.131.52) was purified to homogeneity from the extremely thermophilic, strictly anaerobic, sulfate-reducing archaeon Archaeoglobus fulgidus strain 7324. The native enzyme (263 kDa) is composed of subunits of mol. mass 46 kDa, suggesting a hexameric structure. The temperature optimum for enzyme activity was > 95 degrees C. The enzyme was highly thermostable, having a half-life of 140 min at 100 degrees C. Potassium phosphate, KCl, and NaCl enhanced the thermal stability and increased the rate of activity three- to fourfold. The N-terminal 26-amino-acid sequence showed a high degree of similarity to glutamate dehydrogenases from Pyrococcus spp. and Thermococcus spp.


Linkage disequilibrium reveals different demographic history in egg laying chickens.
The availability of larger-scale SNP data sets in the chicken genome allows to achieve a higher resolution of the pattern of linkage disequilibrium (LD). In this study, 36 k and 57 k genotypes from two independent genotyping chips were used to systematically characterize genome-wide extent and structure of LD in the genome of four chicken populations. In total, we analyzed genotypes of 454 animals from two commercial and two experimental populations of white and brown layers which allows to some extent a generalization of the results. The number of usable SNPs in this study was 19 k to 37 k in brown layers and 8 k to 19 k in white layers. Our analyzes showed a large difference of LD between the lines of white and brown layers. A mean value of r2 = 0.73 ± 0.36 was observed in pair-wise distances of < 25 Kb for commercial white layers, and it dropped to 0.60 ± 0.38 with distances of 75 to 120 Kb, the interval which includes the average inter-marker space in this line. In contrast, an overall mean value of r2= 0.32 ± 0.33 was observed for SNPs less than 25 Kb apart from each other and dropped to 0.21 ± 0.26 at a distance of 100 kb in commercial brown layers. There was a remarkable similarity of the LD patterns among the two populations of white layers. The same was true for the two populations of brown layers, while the LD pattern between white and brown layers was clearly different. Inferring the population demographic history from LD data resulted in a larger effective population size in brown than white populations, reflecting less inbreeding among brown compared to white egg layers. We report comprehensive LD map statistics for the genome of egg laying chickens with an up to 3 times higher resolution compared to the maps available so far. The results were found to be consistent between analyzes based on the parallel SNP chips and across different populations (commercial vs. experimental) within the brown and the white layers. It is concluded that the current density of usable markers in this study is sufficient for association mapping and the implementation of genomic selection in these populations to achieve a similar accuracy as in implementations of association mapping and genomic selection in mammalian farm animals.


Reinvestigation of the tonic natriuretic action of intrarenal dopamine: comparison of two variants of salt-dependent hypertension and spontaneously hypertensive rats.
The intrarenal dopamine system has been thoroughly investigated at all levels, especially its role in salt-dependent and other forms of hypertension. However, the evidence regarding dopamine's tonic influence on renal tubular transport of sodium remains equivocal. We reinvestigated its tonic influence on sodium excretion and systemic and renal haemodynamics. Early effects of dopamine D1 receptor blockade using 90-min Schering 23390 (SCH) infusion were examined in anaesthetized rats on 7 days' high salt diet (HS), early uninephrectomized rats on 14 days' HS diet, drinking 1% saline (HS/UNX), and in spontaneously hypertensive rats (SHR). In the HS group (baseline BP ~133 mm Hg) renal intracortical SCH promptly decreased sodium, water and total solute excretion (UNa V, V, Uosm V), with significant difference from the solvent-infused group. BP and renal artery blood flow (RBF, Transonic probe) did not change. In HS/UNX model (baseline BP ~150 mm Hg), characterized by hypertrophy of the remaining kidney, the excretion parameters only tended to decrease whereas SCH induced an ~20% fall in RBF. In SHR (BP ~180 mm Hg), UNa V and V tended to increase in solvent-infused rats; this increasing tendency was abolished by SCH infusion. During experiments the renal vascular resistance increased significantly in SCH- and solvent-infused SHR. Despite some contradictory findings regarding the genuine tonic control of renal excretion by intrarenal dopamine, our results clearly support such role in rats on HS diet and in SHR, the model resembling human essential hypertension. The observations strengthen the experimental basis and the rationale for targeting the intrarenal dopamine system in attempts to combat arterial hypertension.


Hematological indices and abnormalities among patients with uncomplicated falciparum malaria in Kosti city of the White Nile state, Sudan: a comparative study.
Hematological abnormalities are common features in falciparum malaria but vary among different populations across countries. Therefore, we compared hematological indices and abnormalities between Plasmodium falciparum-infected patients and malaria-negative subjects in Kosti city of the White Nile State, Sudan. A comparative, cross-sectional study was conducted at the Clinical Laboratory Unit of Kosti Teaching Hospital from June to December 2018. A total of 392 participants (192 P. falciparum-infected patients and 200 malaria-negative subjects) were recruited in the study. Hematological indices of hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets were measured, and their median values were statistically compared. The majority of P. falciparum-infected patients (67.6%) showed a low-level parasitemia. The median values of Hb concentration, RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were significantly lower in P. falciparum-infected patients, while the median red cell distribution width (RDW) was significantly higher in the patients compared to malaria-negative subjects. Anemia, low MCV, low MCH, low MCHC and high RDW were significantly associated with falciparum malaria, but parasitemia level was not significantly associated with anemia severity. The median total WBC count was non-significantly higher in P. falciparum-infected patients, with neutropenia being significantly associated with falciparum malaria. The median platelet count was significantly lower in P. falciparum-infected patients, with thrombocytopenia being significantly associated with falciparum malaria. Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria. Further large-scale studies in community and healthcare settings and inclusion of patients with complicated or severe malaria and those with high parasite densities are recommended.


Biological computation running on quantum computation.
Biological computation supporting biological phenomena functionally practices the underlying quantum computation indexically, rather than symbolically. An advantage of the indexical operation of quantum computation rests upon a significant reduction of the computational complexity compared with the corresponding classical counterpart running exclusively upon the symbol manipulation. The reduction of the complexity is sought in allowing for the participation of multiple processors running concurrently in a parallel manner. The concurrent distribution of multiple processors operating mutually in an inseparable manner lets each processor regard the rest of the distribution as its own environment. The environment thus formed and detected by each processor may differ from the similar ones appropriated to the other individual participants nearby. Both the individual processor and the corresponding environment turn out to be agential. Quantum computation practiced indexically may serve as a precursor agency apt for both forming Jakob von Uexküll's umwelt towards the environment and making use of James J. Gibson's affordance from the environment. The individual environment to each material participant there is already indexically agential in pulling that participant in.


Mastication, swallowing, and salivary flow in patients with head and neck cancer: objective tests versus patient-reported outcomes.
Before and after treatment for head and neck cancer (HNC), many patients have problems with mastication, swallowing, and salivary flow. The aim of this study was to investigate the association between objective test outcomes of mastication, swallowing, and salivary flow versus patient-reported outcomes (PROs) measuring mastication-, swallowing-, and salivary flow-related quality of life. Data of the prospective cohort "Netherlands Quality of Life and Biomedical Cohort Study" was used as collected before treatment, and 3 and 6 months after treatment. Spearman's rho was used to test the association between objective test outcomes of the mixing ability test (MAT) for masticatory performance, the water-swallowing test (WST) for swallowing performance, and the salivary flow test versus PROs (subscales of the EORTC QLQ-H&N35, Swallow Quality of Life questionnaire (SWAL-QoL-NL) and Groningen Radiation-Induced Xerostomia (GRIX)). Data of 142 patients were used, and in total, 285 measurements were performed. No significant correlations were found between the MAT or WST and subscales of the EORTC QLQ-H&N35. Significant but weak correlations were found between the MAT or WST and 4 subscales of the SWAL-QoL-NL. Weak to moderate correlations were found between the salivary flow test and GRIX at 3 and 6 months after treatment, with the highest correlation between salivary flow and xerostomia during the day (Spearman's rho = - 0.441, p = 0.001). The association between objective test outcomes and PROs is weak, indicating that these outcome measures provide different information about masticatory performance, swallowing, and salivary flow in patients with HNC.


Non-Hodgkin's lymphomas in children. I. Patterns of disease and classification.
Non-Hodgkin's lymphomas (NHL) are part of an overlapping spectrum of lympho-proliferative diseases in childhood. In the first of this 2 part series, the clinicopathological aspects of NHL in childhood are discussed. The rapid progression of disease, the high incidence of micrometastases (over 80%) at diagnosis, and the propensity of hematogenous spread to the bone marrow and the central nervous system (CNS) as well as the clinico-pathologic 'clusters' associated with particular presenting sites distinguish the pediatric forms of disease. Abdominal primary sites most frequently manifest diffuse undifferentiated (Burkitt's or non-Burkitt's) histopathology, B-cell immunophenotype, FAB-L3 cytomorphology and specific karyotypic and/or genotypic alterations of the immuno-globulin genes and the c-myc oncogene. Mediastinal presentation is associated with lymphoblastic histopathology, T-cell immunophenotype and a variety of less consistent karyotypic and genotypic aberrations. Ki-1 lymphoma, a rare subtype of large cell NHL with specific features is often of T cell origin. The requirements for diagnosis, staging and monitoring are presented in the context of the associations between clinico-pathological presentation and subsequent behavior. The most frequent sites of disease progression and relapse are involvement of the bone marrow and the CNS. For Burkitt's lymphoma there is a historic perspective and a description of particular epidemiologic, clinical, virologic, immunophenotypic and genotypic features. Cytogenetic and molecular biologic studies of genomic rearrangements are advancing the understanding of oncogenesis, clonality, lineage, and clinical behavior. The capacity to detect and amplify DNA from submicroscopic disease may contribute to prognostic stratification both at diagnosis and during subsequent monitoring.


Tryptamine-based human beta3-adrenergic receptor agonists. Part 2: SAR of the methylene derivatives.
A series of tryptamine derivatives with modified sulfonamide were designed, synthesized, and evaluated for their ability to stimulate cAMP accumulation in CHO cells expressing the cloned human beta3-adrenergic receptor (AR). For this series of compounds, our objective was to symmetrize the alpha-position of the tryptamine moiety maintaining its activity and reducing the cost of production. Compound 11h, having m-aminobenzene, exhibited excellent agonistic activity for beta3-AR with excellent subtype selectivity.


Cost of illness and its predictors for Parkinson's disease in Germany.
To prospectively evaluate the health economic burden of patients with Parkinson's disease (PD) in Germany over a 6-month observation period and to identify the predictors of these costs. Direct and indirect costs were evaluated in 145 patients with PD (mean age 67.3 +/- 9.6 years). PD patients were recruited from an outpatient department for movement disorders, a specialised PD clinic, two office-based neurologists and general practitioners, all located in Germany, and were enrolled between January and June 2000. Relevant economic data were documented in a patient diary over the 6-month period. Clinical evaluations (Unified Parkinson's Disease Rating Scale [UPDRS]) were performed at baseline and at 3 and 6 months. Costs were derived from various German medical economic resources. Costs were calculated from the perspective of healthcare and transfer payment providers and the individual patient. Indirect costs for lost productivity were also calculated. Costs are presented as means +/- standard deviation (SD). Multivariate regression analyses were performed to identify independent cost predictors. Costs are in year 2000-02 values. We estimated average per patient direct, indirect and total costs for the 6-month observation period. The costs from the perspective of statutory health insurance (Gesetzliche Krankenkversicherung [GKV]) consisted of direct medical costs 1370 euro +/- 3240 euro, including rehabilitation (420 euro +/- 1630 euro), hospitalisation (710 euro +/-2520 euro), outpatient treatment (40 euro +/- 30 euro), ancillary treatment (190 euro +/- 280 euro) and ambulatory diagnostic procedures (10 euro +/-30 euro). In addition, parkinsonian drug costs were 1520 euro +/-euro1250. Non-medical direct costs calculated from the GKV perspective were estimated to be euro480 +/-euro1710, which included transportation (10 euro+/- 20 euro), special equipment (420 euro +/- 1640 euro), social/home-help services (10 euro +/-110 euro) and sickness benefit (40 euro +/- 540 euro). The total medical (including drug costs) and non-medical direct costs for the GKV were 3380 euro +/- 4230 euro. Univariate predictors for GKV direct costs included occurrence of motor complications and falls, disease severity, nightmares and dementia. However, multivariate analyses only suggested disease severity and health-related quality of life as significant predictors. For nursing insurance, payments of 1330 euro +/- 2890 euro were calculated. For retirement insurance, payments were 650 euro +/- 1510 euro and there were patient (or caregiver) costs of 1490 euro +/- 2730 euro. Total indirect costs amounted to 3180 euro +/-6480 euro. According to our study, PD puts a high financial burden on society and underscores the need for further economic and medical research to optimise treatment for PD.