Impact of the glpQ2 gene on virulence in a Streptococcus pneumoniae serotype 19A sequence type 320 strain.
Glycerophosphodiester phosphodiesterase (GlpQ) metabolizes glycerophosphorylcholine from the lung epithelium to produce free choline, which is transformed into phosphorylcholine and presented on the surfaces of many respiratory pathogens. Two orthologs of glpQ genes are found in Streptococcus pneumoniae: glpQ, with a membrane motif, is widespread in pneumococci, whereas glpQ2, which shares high similarity with glpQ in Haemophilus influenzae and Mycoplasma pneumoniae, is present only in S. pneumoniae serotype 3, 6B, 19A, and 19F strains. Recently, serotype 19A has emerged as an epidemiological etiology associated with invasive pneumococcal diseases. Thus, we investigated the pathophysiological role of glpQ2 in a serotype 19A sequence type 320 (19AST320) strain, which was the prevalent sequence type in 19A associated with severe pneumonia and invasive pneumococcal disease in pediatric patients. Mutations in glpQ2 reduced phosphorylcholine expression and the anchorage of choline-binding proteins to the pneumococcal surface during the exponential phase, where the mutants exhibited reduced autolysis and lower natural transformation abilities than the parent strain. The deletion of glpQ2 also decreased the adherence and cytotoxicity to human lung epithelial cell lines, whereas these functions were indistinguishable from those of the wild type in complementation strains. In a murine respiratory tract infection model, glpQ2 was important for nasopharynx and lung colonization. Furthermore, infection with a glpQ2 mutant decreased the severity of pneumonia compared with the parent strain, and glpQ2 gene complementation restored the inflammation level. Therefore, glpQ2 enhances surface phosphorylcholine expression in S. pneumoniae 19AST320 during the exponential phase, which contributes to the severity of pneumonia by promoting adherence and host cell cytotoxicity.


Molecular constraints on resistance-tolerance trade-offs.
Plants have numerous mechanisms to cope with the negative effects of herbivory, including plant resistance, structural and chemical traits that reduce damage, and plant tolerance, the ability to compensate for tissues lost. It has been argued that resistance and tolerance represent alternate strategies and thus there should be a trade-off between resistance and tolerance. However, resistance and tolerance are controlled via the same molecular pathway, the oxidative pentose phosphate pathway and the process of endoreduplication. Endoreduplication is the replication of the genome without mitosis, which leads to an increase in cellular chromosome number. Increasing chromosome number and therefore gene copy number provides a means of increasing gene expression that has been shown to enhance compensation following herbivory. By measuring glucosinolate levels and seed production following the removal of apical dominance in genotypes of Arabidopsis thaliana we show that there is a positive association between tolerance and induced chemical defense. Similarly, the direct association between tolerance and resistance is demonstrated by genetically manipulating the endoreduplication pathway. By overexpressing ILP1, a positive regulator of endoreduplication, and thus compensation, we experimentally increased glucosinolate production and tolerance in the Col-0 genotype. We suggest that many herbaceous plants that endoreduplicate (~90%) would show a positive relationship between compensation and chemical defense, given that the molecular pathways are shared in common. We discuss these findings in light of contrasting results on measures of tolerance and resistance, given that the true relationship can be masked by ignoring genetic variation in endoreduplication and the timing of chemical measurement.


Human plasma fibrinogen measurement derived from activated partial thromboplastin time clot formation.
Prothrombin time-derived measurement of fibrinogen (PTd) has already been described. Activated partial thromboplastin time-derived measurement of fibrinogen (aPTTd) has not yet been clearly defined. Using an MDA II coagulometer (Organon Teknika, Durham, North Carolina, USA), we have therefore compared fibrinogen levels determined with Clauss, PTd, and aPTTd assays and an enzyme immunoassay (EIA) in 172 samples. Of these, 47 were from pre-operative controls, 18 from patients with liver disease, 28 from patients with hyperfibrinogenaemia, 33 from patients treated with vitamin K antagonists, 22 from patients treated with unfractionated heparin and 24 from haemophilic patients. Within the normal range, interassay and intra-assay variations were comparable. For control samples, PTd, aPTTd and Clauss assays were well correlated, without any systematic error. EIA was also correlated but values were slightly higher (mean of difference = 0.24). Pathological samples showed an overestimation of fibrinogen when using PTd measurements in patients treated with vitamin K antagonists, as well as when using aPTTd measurements in patients presenting with factor VIII and factor IX deficiencies. These results indicate that, despite expected financial savings, aPTTd fibrinogen measurements should not be used without restriction. PTd and aPTTd fibrinogen determinations are provided without any additional cost. Their comparison with Clauss fibrinogen results may constitute a validation tool or have additional diagnostic utility (e.g. identifying polymerization abnormalities in case of dissimilar results).


Development of an alternating integrator for magnetic measurements for experimental advanced superconducting tokamak.
A high-performance integrator is one of the key electronic devices for reliably controlling plasma in the experimental advanced superconducting tokamak for long pulse operation. We once designed an integrator system of real-time drift compensation, which has a low integration drift. However, it is not feasible for really continuous operations due to capacitive leakage error and nonlinearity error. To solve the above-mentioned problems, this paper presents a new alternating integrator. In the new integrator, the integrator system of real-time drift compensation is adopted as one integral cell while two such integral cells work alternately. To achieve the alternate function, a Field Programmable Gate Array built in the digitizer is utilized. The performance test shows that the developed integrator with the integration time constant of 20 ms has a low integration drift (<15 mV) for 1000 s.


Perceptions of provider communication and patient satisfaction for treatment of acute low back pain.
We sought to assess the relationship between perceptions of provider communication and treatment satisfaction for acute, work-related low-back pain (LBP). In a prospective cohort study, 544 working adults (67% men) with acute LBP provided 1- and 3-month assessments of pain, function, and work status. In a multiple regression analysis, positive provider communication (took problem seriously, explained condition clearly, tried to understand my job, advised to prevent re-injury) explained more variation in patient satisfaction at 1 month than was explained by clinical improvements in pain and function. At 3 months, clinical improvement variables surpassed provider communication as predictors of patient satisfaction. Patients with work-related LBP place a high value on provider counseling and education, especially during the acute stage (<1 month) of treatment.


Impact of MAC Delay on AUV Localization: Underwater Localization Based on Hyperbolic Frequency Modulation Signal.
Medium Access Control (MAC) delay which occurs between the anchor node's transmissions is one of the error sources in underwater localization. In particular, in AUV localization, the MAC delay significantly degrades the ranging accuracy. The Cramer-Rao Low Bound (CRLB) definition theoretically proves that the MAC delay significantly degrades the localization performance. This paper proposes underwater localization combined with multiple access technology to decouple the localization performance from the MAC delay. Towards this goal, we adopt hyperbolic frequency modulation (HFM) signal that provides multiplexing based on its good property, high-temporal correlation. Owing to the multiplexing ability of the HFM signal, the anchor nodes can transmit packets without MAC delay, i.e., simultaneous transmission is possible. In addition, the simulation results show that the simultaneous transmission is not an optional communication scheme, but essential for the localization of mobile object in underwater.


Generalized box-plot for root growth ensembles.
In the field of root biology there has been a remarkable progress in root phenotyping, which is the efficient acquisition and quantitative description of root morphology. What is currently missing are means to efficiently explore, exchange and present the massive amount of acquired, and often time dependent root phenotypes. In this work, we present visual summaries of root ensembles by aggregating root images with identical genetic characteristics. We use the generalized box plot concept with a new formulation of data depth. In addition to spatial distributions, we created a visual representation to encode temporal distributions associated with the development of root individuals. The new formulation of data depth allows for much faster implementation close to interactive frame rates. This allows us to present the statistics from bootstrapping that characterize the root sample set quality. As a positive side effect of the new data-depth formulation we are able to define the geometric median for the curve ensemble, which was well received by the domain experts.


Emulsion stability, thermo-rheology and quality characteristics of ground pork patties prepared with soy protein isolate and carrageenan.
Plant proteins and polysaccharides are often utilised in ground meat products as meat binders, gelling agents, texture stabilisers or fat substitutes. The aim of this study was to investigate the effects of the incorporation of 57 g kg(-1) soy protein isolate (SPI), 7 g kg(-1) carrageenan (CAR) and SPI/CAR mixture on the quality of ground pork patties. Ground pork patties with individual SPI and CAR or SPI/CAR mixture showed either retained or improved emulsion stability, physicochemical properties and dynamic rheology compared with control samples. Although there were no significant colour differences among treatments, samples with SPI/CAR mixture presented higher texture profile values for hardness and chewiness compared with other treatments (P < 0.05). Patties with additives showed significantly lower cooking loss and better thermal emulsion stability than control samples owing to a lower release rate of water and fat (P < 0.05). Compared with control samples or those with individual SPI and CAR, patties with SPI/CAR mixture formed a smoother and more continuous structure with a more compact protein matrix. The results indicate that a mixture of SPI and CAR can be effectively used as a functional ingredient to improve the quality of ground pork patties.


Pulmonary venous blood flow pattern in patients with univentricular hearts following total cavo-pulmonary connection.
The objective of the study was evaluation of the pulmonary venous blood flow (PVF) pattern and the influence of ventricular function and atrioventricular valve regurgitation on this flow in patients with univentricular hearts post total cavo-pulmonary connection (TCPC). Transthoracic or transoesophageal echocardiographic studies were performed in 24 children with normal hearts (group A) and in 24 patients with univentricular hearts (group B). Ventricular function and atrioventricular valve regurgitation was semiquantitatively assessed. Systolic/diastolic maximal velocities and velocity time integrals (VTI) were measured from PVF tracings. Ejection fraction was measured by radionuclide angiography in 11 patients. Twelve patients underwent heart catheterization and angiography. In group B the PVF showed a biphasic flow velocity curve. The systolic integrals were smaller and the diastolic integrals were larger than in group A (6.4 vs. 13.0 cm, P = 0.0001, and 13.9 vs. 10.0 cm, P = 0.005). The pulmonary venous systolic flow fraction in 13 patients with an open fenestration and/or atrioventricular valve regurgitation grade 2-3 was significantly lower than in those 11 patients without fenestration and none/small regurgitation (0.19 vs. 0.40, P = 0.05). In conclusion, the PVF pattern in children with univentricular hearts pallitated with TCPC is similar to the PVF pattern found in individuals with biventricular hearts showing a biphasic flow velocity curve despite the absence of pulsatile pulmonary artery flow. The PVF in patients with TCPC-palliated univentricular hearts is influenced by atrioventricular valve regurgitation and fenestration flow.


Biochemical and functional comparisons of Mcl-1 and Bcl-2 proteins: evidence for a novel mechanism of regulating Bcl-2 family protein function.
Mcl-1 is a recently described homologue of Bcl-2 whose function and biochemical characteristics remain poorly defined. Gene transfer experiments in lnterleukin-3 (IL-3)-dependent myeloid progenitor 32D.3 cells and pro-B-lymphoid FL5.12 cells demonstrated that enforced production of high levels of Mcl-1 protein failed to prolong the survival of cells when cultured in the absence of IL-3, whereas Bcl-2 did delay cell death. Mcl-1 also did not prolong the survival in vitro of 32D.3 cells that had been induced to differentiate into mature neutrophils using Granulocyte-Colony Stimulating Factor (G-CSF), whereas Bcl-2 did. 32D.3 and FL5.12 cells co-transfected with Mcl-1 and Bcl-2 displayed survival kinetics essentially identical to cells transfected with Bcl-2 alone, when cultured in the absence of IL-3, indicating that Mcl-1 neither enhances nor impairs Bcl-2 function. In contrast to the lack of effects of Mcl-1 in 32D.3 and FL5.12 cells, Mcl-1 (like Bcl-2) was able to neutralise Bax-induced cytotoxicity in yeast (S. cerevisiae). Moreover, the recombinant GST-Mcl-1 protein bound specifically to in vitro translated Bax protein, as well as to Bax protein present in detergent lysates prepared from 32D.3 and FL5.12 cells, based on in vitro binding assays. However, Mcl-1 and Bax proteins could not be co-immunoprecipitated from control and transfected 32D.3 and FL5.12 cells, whereas Bcl-2 and Bax were easily co-immunoprecipitated under the same conditions. The findings suggest that while Mcl-1 has the capacity to bind to and neutralise the cell death promoting activity of Bax, other factors such as perhaps additional proteins or undefined post-translational modifications may influence its ability to bind to Bax in vivo and thus affect its function as a cell death blocker.


A Longitudinal Study on Maternal Depressive Symptoms During the COVID-19 Pandemic: The Role of Strict Lockdown Measures and Social Support.
Objectives: This study examined the trajectory of perinatal depressive symptoms in Portuguese women during the COVID-19 pandemic and the role of individual, relational, and contextual risk and protective factors. Methods: This 3-wave longitudinal study followed 290 pregnant women from the third trimester of pregnancy until 6-months postpartum. Women self-reported on depressive symptoms, psychological (anxiety, perceived stress, mindfulness), relational (perceived social support, dyadic adjustment, sexual wellbeing), and contextual (lockdown status) factors. Results: Women who were under strict lockdown presented significantly higher scores of depressive symptoms at baseline (by 1.38 EPDS points) than women who were not under strict lockdown measures. Mixed Growth Models showed that trajectories of depressive symptoms were explained by differences in women's baseline depression. Differences in women's depressive symptoms at baseline were mainly explained by higher anxiety and lower social support (22% and 24% for women under lockdown; 39% and 6% for women not on lockdown, respectively). Conclusion: Preventative interventions targeted at pregnant women should aim to reduce anxiety and enhance women's social support to prevent depression in pregnancy and postpartum during the COVID-19 pandemic.


[Sports death--an Internal Medicine problem?].
Sports means fitness and endurance, regeneration and balance, game and fun. Lack of physical exercise is one of the main risk factors for cardiovascular diseases. Terrifying and not conclusive in the public's mind are events of sudden death, in particular if those are of nontraumatic cause and thus of cardiovascular origin. Organic pathologic examination revealed that a higher proportion of males are affected by sports death. Only 7-9% of those events are related to women, although the percentage of active women among sports people accounts for nearly 50%. The relative risk increases with age and intensity of endurance. For people who are untrained or not used to train, the risk of sudden death is potentially higher. In athletes > 35 years of age, coronary artery disease (CAD) is the most common cause (85%) of sudden death. In the group < 35 years, CAD and acute myocarditis are the predominant causes of sudden death, but also hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), disorders of the conducting system, and Marfan's syndrome. Additional risk factors like acute infections and misuse of doping drugs require the care of a specialist in internal medicine and/or cardiology on top of the care by a specialist in orthopedics and accident/rehabilitation medicine. Physical examination as a precaution and prevention strategy should be available for leisure sports as well as for athlete sports.


Preparation of Gas-Responsive Imprinting Hydrogel and Their Gas-Driven Switchable Affinity for Target Protein Recognition.
Novel gas-responsive imprinting hydrogels were fabricated by combining N,N'-dimethylaminoethyl methacrylate gas-sensitive monomers, N,N'-methylenebis(acrylamide) cross-linkers, and human serum albumin (HSA) template proteins via a free radical polymerization. The hydrogel exhibited a reversible gas-responsive property upon N2/CO2 exchange. This result was supported by the evidences from hydrogen nuclear magnetic resonance spectroscopy and scanning electron microscopy. By applying this property to sensing application, a CO2-responsive imprinted biosensor was originally designed on the surface of a glassy carbon electrode. The biosensor exhibited unique self-clean and self-recognition properties toward HSA proteins based on reversible conformational changes driven by N2/CO2 stimuli. Moreover, the proposed imprinted biosensor favored HSA proteins by showing satisfactory sensitivity and selectivity and a wider detection range with a low detection limit. As a rare example in imprint sensing, the biosensor was successfully applied to the HSA extraction from complex serum samples. With gas stimuli, the whole process was efficient, controllable, and harmless to the proteins. Thus, the developed biosensor may provide a new prospect in molecularly imprinted sensing applications.


Multiplexed miRNA Quantitation Using Injectionless Microfluidic Thermal Gel Electrophoresis.
MicroRNAs (miRNAs) are a class of biomolecules that have high clinical and pharmaceutical significance because of their ability to regulate protein expression. Better methods are needed to quantify target miRNAs, but their similar sequence lengths and low concentrations in biomedical samples impede analysis. This report aimed to develop a simple, rapid method to directly quantify multiple miRNAs using microfluidic thermal gel electrophoresis (TGE). Fluorescent probes were designed complementarily in sequence to four target miRNAs that also contained variable DNA overhangs to alter their electrophoretic mobilities. Samples and probes were directly added into thermal gel and loaded throughout a microchannel. Applying voltage resulted in an inline preconcentration and separation of the miRNAs that did not require a sample injection nor user intervention to switch between modes. Baseline resolution was achieved between four double-stranded miRNA-probe hybrids and four excess single-stranded probes. Analytical performance was then improved by designing an innovative microfluidic device with a tapered channel geometry. This device exhibited superior detection limits and separation resolution compared to standard channel devices without increasing the complexity of microfabrication or device operation. A proof-of-concept demonstration was then performed, showing that target miRNAs could be detected from cell extracts. These results demonstrate that TGE provides a simple, inexpensive means of conducting multiplexed miRNA measurements, with the potential for automation to facilitate future clinical and pharmaceutical analyses.


Social and psychological effects of the COVID-19 pandemic on middle-school students: Attendance options and changes over time.
The purpose of this study was to determine whether restrictions put in place during the COVID-19 pandemic affected the social and psychological well-being of early adolescent schoolchildren. Participants were 309 youth (51% female, average age = 12.38 years) enrolled in the sixth, seventh, or eighth grades of a single middle school located in northeastern Pennsylvania, a state that took a moderately proactive approach to the pandemic. Employing a cross-sectional design, students in three instructional conditions (100% in-person, hybrid, 100% online) were compared on nine outcome measures (perceived parental support, perceived parental knowledge, peer deviance, neutralization, cognitive impulsivity, depression, delinquency, bullying victimization, and bullying perpetration). There were no significant between-groups differences, although there was a borderline significant effect for depression (100% online > 100% in-person, p = .06). A second set of analyses employed a longitudinal design and compared 174 children who completed the test battery in November 2019, 3 months before the start of the pandemic, and then again in November 2020, 9 months after the start of the pandemic. Three out of nine outcomes displayed significant change: A small reduction in parental support and modest increments in neutralization beliefs and cognitive impulsivity. Although there were no statistically significant differences between the three instructional conditions and only a handful of relatively small and predictable longitudinal changes between November 2019 and November 2020, there were a fair number of individual students who experienced moderate (≥ 50%) increases in depression (17.6%), cognitive impulsivity (15.8%), and bullying victimization (11.7%). (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The cost of diabetes in Canada over 10 years: applying attributable health care costs to a diabetes incidence prediction model.
Our objective was to estimate the future direct health care costs due to diabetes for a 10-year period in Canada using national survey data, a validated diabetes risk prediction tool and individual-level attributable cost estimates. We used the Diabetes Population Risk Tool to predict the number of new diabetes cases in those aged 20 years and above over a 10-year period (to 2022), using 2011 and 2012 Canadian Community Health Survey data. We derived attributable costs due to diabetes from a propensity-matched case control study using the Ontario Diabetes Database and other administrative data. We calculated total costs by applying the respective attributable costs to the incident cases, accounting for sex, year of diagnosis and annual disease-specific mortality rates. The predicted 10-year risk of developing diabetes for the Canadian population in 2011/12 was 9.98%, corresponding to 2.16 million new cases. Total health care costs attributable to diabetes during this period were $7.55 billion for females and $7.81 billion for males ($15.36 billion total). Acute hospitalizations accounted for the greatest proportion of costs (43.2%). A population intervention resulting in 5% body weight loss would save $2.03 billion in health care costs. A 30% risk-reduction intervention aimed at individuals with the highest diabetes risk (i.e. the top 10% of the highest-risk group) would save $1.48 billion. Diabetes represents a heavy health care cost burden in Canada through to the year 2022. Our future cost calculation method can provide decision makers and planners with an accessible and transparent tool to predict future expenditures attributable to the disease and the corresponding cost savings associated with interventions.


Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy.
In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core-shell nanoparticles are attached to the graphene oxide (GO) sheet via π-π stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug-loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine.


Associations between socioeconomic factors and depression in Sri Lanka: The role of gene-environment interplay.
Low socioeconomic status is a risk factor for depression. The nature and magnitude of associations can differ cross-culturally and is influenced by a range of contextual factors. We examined the aetiology of socioeconomic indicators and depression symptoms and investigated whether socioeconomic indicators moderate genetic and environmental influences on depression symptoms in a Sri Lankan population. Data were from a population-based sample of twins (N = 2934) and singletons (N = 1035) in Colombo, Sri Lanka. Standard of living, educational attainment, and financial strain were used to index socioeconomic status. Depression symptoms were assessed using the Revised Beck Depression Inventory. Structural equation modelling explored genetic and environmental influences on socioeconomic indicators and depression symptoms and moderation of aetiological influences on depression symptoms by socioeconomic status. Depression symptoms were associated with lower standard of living, lower educational attainment, and financial strain. Sex differences were evident in the aetiology of standard of living, with a small contribution of genetic influences in females. Educational attainment was moderately heritable in both males and females. Total variance in depression was greater among less socioeconomically advantaged individuals. Modest evidence of moderation of the aetiology of depression by standard of living and education was observed. While the sample is representative of individuals living in Colombo District, it may not be representative of different regions of Sri Lanka. The aetiology of depression varies across socioeconomic contexts, suggesting a potential mechanism through which socioeconomic disadvantage increases the risk for depression in Sri Lanka. Findings have implications for cross-cultural investigations of the role of socioeconomic factors in depression and for identifying targets for social interventions.


Determination of acoustic nonlinearity parameter (β) using nonlinear resonance ultrasound spectroscopy: Theory and experiment.
The present article investigates the possibility of using nonlinear resonance ultrasound spectroscopy to determine the acoustic nonlinearity parameter (β) and third order elastic constant by developing an inverse problem. A theoretical framework was developed for nonlinear forced vibration of a cantilever beam using material nonlinearity (stress-strain nonlinearity). The resulting nonlinear equation was solved using method of multiple time scales to obtain the nonlinear frequency shifts. The present works focuses only on classical nonlinearity and, therefore, a diverse group of intact, classic nonlinear materials were chosen. The samples were tested using nonlinear resonance ultrasound spectroscopy, and the developed theory was used to invert the experimental frequency shifts to obtain the nonlinearity parameters. The third order elastic constants and β were calculated using their analytical relationship with the nonlinearity parameter. The experimentally determined C111 and β values for all various materials agree well with literature values. In addition to determining β, determination of the sign, or phase of β was also explored theoretically and experimentally.


Modern management of external genital warts.
External genital warts are a significant health problem particularly for young adults. This review summarizes the current literature on epidemiology, transmission, diagnosis, and treatment. Efficacy of all treatments is less than optimal, and multiple therapies may be necessary for complete resolution. Data on a new patient-applied therapy are presented. New vaccine therapy for prevention of infection should reduce the incidence of disease.


Structure determination of L-arabinitol by powder X-ray diffraction.
Powder X-ray diffraction patterns of the commercial phase of L-arabinitol were recorded with a laboratory diffractometer. The starting structural model was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with soft restraints on the interatomic bond lengths and bond angles. H atoms of hydroxyl groups were localized by minimization of the crystalline energy. The cell is triclinic with the space group P1 and contains two molecules. The crystalline cohesion is achieved by an important network of O-H···O hydrogen bonds.


Locality in amino-acid based imidazolium ionic liquids.
Several amino-acid based imidazolium ILs are investigated through the use of ab initio molecular dynamics (AIMD), which includes full polarization. The electric dipole moment distribution and polarization is used as a means of characterizing and understanding these complex systems. Various charge scheme methods were analyzed (Wannier function, Blöchl, Löwdin and Mulliken charge schemes and Voronoi tessellation) to determine their ability to predict dipole moments. These results and the following comparison of methods further deepen the knowledge of polarization by highlighting the importance of the anion and cation separately on polarizability contribution and the need to select a suitable method to predict these. The angular probability distribution is utilized to measure the degree of locality in monopole-dipole electrostatic interactions, which showed no preferential alignment over 700 pm. In addition, the IR and Raman spectra from Voronoi tessellation of [C2C1Im][ala] were analyzed. In these, the strongest signalling peaks showed consistency with experiment and the ability to differentiate between anion and cation components of the IL.


Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro.
It is still not entirely clear how α-galactosidase A (GAA) deficiency translates into clinical symptoms of Fabry disease (FD). The present communication investigates the effects of the mutation N215S in FD on the trafficking and processing of lysosomal GAA and their potential association with alterations in the membrane lipid composition. Abnormalities in lipid rafts (LRs) were observed in fibroblasts isolated from a male patient with FD bearing the mutation N215S. Interestingly, LR analysis revealed that the distribution of cholesterol and flotillin-2 are distinctly altered in the Fabry fibroblasts when compared with that of the wild-type cells. Furthermore, increased levels of glycolipid globotriaosylceramide 3 (Gb3) and sphingomyelin (SM) were observed in non-raft membrane fractions of Fabry cells. Substrate reduction with N-butyldeoxynojirimycin (NB-DNJ) in vitro was capable of reversing these abnormalities in this patient. These data led to the hypothesis that alterations of LRs may contribute to the pathophysiology of Morbus Fabry. Furthermore, it may be suggested that substrate reduction therapy with NB-DNJ might be a promising approach for the treatment of GAA deficiency at least for the selected patients.


Therapy Adjustments Based on Trend Arrows Using Continuous Glucose Monitoring Systems.
Continuous glucose monitoring (CGM) systems use trend arrows to accurately display the anticipated glucose curve for the user. These are used for both "real-time" glucose monitoring and for intermittent scanning glucose monitoring. Trend arrow data are used by people with diabetes to make corrections to their glucose control. It is essential that they are correctly interpreted when adjusting insulin doses and to ensure that appropriate treatment decisions are made. The aim of this article is to provide general treatment guidance for diabetes teams and for people with diabetes using CGM in the context of trend arrows. This is based on previous recommendations for interpreting trend arrows without losing sight of the need for individual therapy adjustment.


White matter abnormalities in paediatric obsessive-compulsive disorder: a systematic review of diffusion tensor imaging studies.
Microstructural alterations in white matter are evident in obsessive-compulsive disorder (OCD) both in adult and paediatric populations. Paediatric patients go through the process of maturation and thus may undergo different pathophysiology than adult OCD. Findings from studies in paediatric obsessive-compulsive disorder have been inconsistent, possibly due to their small sample size or heterogeneous populations. The aim of this review is to provide a comprehensive overview of white matter structures in paediatric obsessive-compulsive disorder and their correlation with clinical features. Based on PRISMA guidelines, we performed a systematic search on diffusion tensor imaging studies that reported fractional anisotropy, mean diffusivity, radial diffusivity, or axial diffusivity alterations between paediatric patients with obsessive-compulsive disorder and healthy controls using voxel-based analysis, or tract-based spatial statistics. We identified fifteen relevant studies. Most studies reported changes predominantly in the corpus callosum, cingulum, arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, forceps minor and major, and the cerebellum in paediatric obsessive-compulsive disorder. These alterations included increased and decreased fractional anisotropy and radial diffusivity, and increased mean and axial diffusivity in different white matter tracts. These changes were associated with obsessive-compulsive disorder symptoms. Moreover, specific genetic polymorphisms were linked with cerebellar white matter changes in paediatric obsessive-compulsive disorder. White matter changes are widespread in paediatric OCD patients. These changes are often associated with symptoms however there are controversies in the direction of changes in some tracts.


Acceptable results after self-expanding metallic stent treatment for dysphagia in non-resectable oesophageal cancer.
Dysphagia is the most common symptom of malignant obstruction in the oesophagus and at the gastro-oesophageal junction (GEJ) region, and the relief of dysphagia plays a major role in palliative treatment of this condition. The aim of the present study was to evaluate the need for and nature of re-intervention after self-expanding metallic stents (SEMS) insertion in patients who were palliated for cancer of the oesophagus or GEJ. At a third-level referral centre in Denmark, all SEMS procedures were prospectively registered for SEMS characteristics and procedural events and data regarding re-interventions and survival were retrieved retrospectively in a six-year inclusion period. A total of 108 stents were inserted into 87 patients (63 males and 23 females) with a median age of 71 years (range: 41-94 years). The primary SEMS used was Ultraflex in 77, Cook or Choo in seven and Wallstent in three cases. All but one SEMS were successfully placed, and no perforations occurred. Fifty patients had their dysphagia scores recorded. The average score before and after stent insertion was 2.4 and 0.8, respectively, (p < 0.01). Two-thirds of the patients needed late re-interventions. The most common problem was tissue/tumour ingrowth (n = 40). Seven patients (8%) experienced stent migration. The average re-intervention rate was 2.8 per patient. The median survival after SEMS was 116 days (range 2-866 days). The median time to first re-intervention was 44 days. SEMS treatment was a safe and effective palliation of malignant obstruction in the oesophagus and GEJ region, but the procedure was associated with a frequent need for re-interventions.


Psychopathic femicide: The influence of psychopathy on intimate partner homicide.
High scores in psychopathy were associated with acts of violence, and the prevalence of this condition is greater among the prison population than among the general population. In terms of its relation to femicide, two studies, one carried out in Sweden and another in Spain with a prison population, found that psychopathy is an uncommon condition among perpetrators of femicide. This study analyzes 97 cases of femicide in the whole of Spain, in which it was possible to evaluate the degree of psychopathy of the perpetrators using the Psychopathy Checklist-Revised (PCL-R). The scores are analyzed not only directly, but also in terms of Factors and Facets. The results show an average in the total score of the PCL-R of 14.4, with only 13 subjects (13.4%) presenting scores of 25 or more, and just 3 (3.1%) of these presenting scores of 30 or higher. It was found that, in general, high scores in psychopathy are associated with shorter relationships and less time between the first complaint, the breakup, and the femicide. What is more, characteristics of the victims, such as addiction to toxic substances or economic dependency, also demonstrated a relationship to the scores of the perpetrators of femicide in the PCL-R. Lastly, it was found that the scores in the different dimensions of psychopathy are associated with different types of violence, whereby there was a noteworthy difference between the most explicit violence and control exercised over the partner.


Susceptibility of the developing brain to acute hypoglycemia involving A1 adenosine receptor activation.
It has been suggested that the developing brain is less vulnerable to the adverse effects of hypoglycemia than the mature brain; however, this issue remains controversial. We also do not know the magnitude or duration of hypoglycemia needed to trigger hypoglycemic brain injury during development. To address this issue a series of in vivo and in vitro studies were performed. First, we established an acute model of insulin-induced hypoglycemia in mice by administering 3 U/kg of neutral-protamine Hagadorn insulin subcutaneously. When we examined degenerating neurons in hippocampus and striatum by TUNEL labeling, injury was observed after 4 h of hypoglycemia in postnatal day (P)7 mice, and we observed more cell injury in animals rendered hypoglycemic at P7 than at P21. Studies of hippocampal slice cultures revealed that reduction in glucose concentration induced more neuronal injury in slices prepared from P3 and P7 than from P14 and P21 mice. Treatment of slices with an adenosine A(1) receptor (A(1)AR) antagonist reduced the hypoglycemic damage, whereas agonists increased damage, particularly in slices prepared from very young pups. This suggests a critically important role for A(1)ARs, which was further demonstrated by the reduction of hypoglycemic damage in hippocampal slices prepared from A(1)AR(-/-) mice. Furthermore, insulin-induced hypoglycemia in P7 A(1)AR(-/-) mice did not increase TUNEL-positive cells, but a major increase was seen in A(1)AR(+/-) mice. These observations show that the developing nervous system is indeed sensitive to acute hypoglycemic injury and that A(1)AR activation contributes to damage induced by hypoglycemia, particularly in immature mouse brain.


Clinical application of a silk fibroin protein biologic scaffold for abdominal wall fascial reinforcement.
Preclinical studies have demonstrated that macroporous silk fibroin protein scaffolds are capable of promoting physiologically durable supportive tissue, which favors application of these engineered tissues for clinical implantation. The safety and effectiveness of a long-lasting, transitory, 510(k)-cleared purified silk fibroin biologic scaffold (SBS) are investigated for soft-tissue support and repair of the abdominal wall. We conducted a multicenter retrospective review of all consecutive patients who underwent abdominal wall soft-tissue reinforcement with an SBS device between 2011 and 2013. Indications, comorbid conditions, surgical technique, complications, and outcomes were evaluated. We reviewed the records of 172 consecutive patients who received an SBS for soft-tissue support. Of those, 77 patients underwent abdominal wall fascial repair, with a mean follow-up of 18.4 ± 7.5 months. Procedures using an SBS included reinforcement of an abdominal-based flap donor site (31.2%), ventral hernia repair (53.2%), and abdominoplasty (15.6%). The overall complication rate was 6.5%, consisting of 2 wound dehiscences, 1 with device exposure, 1 seroma, 1 infection with explantation, and a perioperative bulge requiring reoperation. There were no reports of hernia. Postoperative complication rates after 18 months were low, and most surgical complications were managed nonoperatively on an outpatient basis without mesh removal. To our knowledge, this is the only series to report on a long-lasting, transitory SBS for abdominal wall repair and reinforcement. Procedure-specific outcome studies are warranted to delineate optimal patient selection and define potential device characteristic advantages.


Decoding the different states of visual attention using functional and effective connectivity features in fMRI data.
The present paper concentrates on the impact of visual attention task on structure of the brain functional and effective connectivity networks using coherence and Granger causality methods. Since most studies used correlation method and resting-state functional connectivity, the task-based approach was selected for this experiment to boost our knowledge of spatial and feature-based attention. In the present study, the whole brain was divided into 82 sub-regions based on Brodmann areas. The coherence and Granger causality were applied to construct functional and effective connectivity matrices. These matrices were converted into graphs using a threshold, and the graph theory measures were calculated from it including degree and characteristic path length. Visual attention was found to reveal more information during the spatial-based task. The degree was higher while performing a spatial-based task, whereas characteristic path length was lower in the spatial-based task in both functional and effective connectivity. Primary and secondary visual cortex (17 and 18 Brodmann areas) were highly connected to parietal and prefrontal cortex while doing visual attention task. Whole brain connectivity was also calculated in both functional and effective connectivity. Our results reveal that Brodmann areas of 17, 18, 19, 46, 3 and 4 had a significant role proving that somatosensory, parietal and prefrontal regions along with visual cortex were highly connected to other parts of the cortex during the visual attention task. Characteristic path length results indicated an increase in functional connectivity and more functional integration in spatial-based attention compared with feature-based attention. The results of this work can provide useful information about the mechanism of visual attention at the network level.


Mucin degradation in human colon ecosystems. Evidence for the existence and role of bacterial subpopulations producing glycosidases as extracellular enzymes.
Recent work indicates that subpopulations of human fecal bacteria, averaging approximately 1% of the total viable fecal flora, degrade the oligosaccharide side chains of hog gastric mucin, which structurally resembles human epithelial mucins. Here we report studies to determine whether degradation of mucin oligosaccharides is related to glycosidase production by bacteria growing in anaerobic fecal cultures. Triplicate cultures containing hog gastric mucin were inoculated with serially diluted feces from each of seven healthy subjects. When the stationary growth phase was attained, mucin oligosaccharide degradation and both cell-bound and extracellular activities of four glycosidases were measured in each culture. Cell-bound beta-d-galactosidase, beta-N-acetylglucosaminidase, and sialidase were present in bacteria growing at all levels of fecal inocula, including 10(-11) g. In contrast, extracellular activities were present in every culture inoculated with 10(-4)-10(-7) g feces, but were diminished or absent in cultures inoculated with 10(-8)-10(-11) g feces. Bacterial autolysis was an unlikely cause of extracellular glycosidase activity, since p-nitrophenyl-alpha-l-fucosidase remained cell bound in cultures at every level of fecal inoculum. Degradation of mucin oligosaccharides was associated with extracellular, but not with cell-bound beta-d-galactosidase, beta-N-acetylglucosaminidase, and sialidase. Among the seven subjects, the estimated most probable numbers (MPN) of fecal bacteria producing extracellular beta-d-galactosidase, beta-N-acetylglucosaminidase, and sialidase ranged from 10(6)-10(10)/g dry fecal wt, were comparable to the MPN of mucin-degrading bacteria, and were significantly smaller than the MPN of total fecal bacteria. We interpret these findings as evidence for the existence of bacterial subpopulations in the normal fecal flora that produce extracellular glycosidases, and that these subpopulations have a major role in degrading the complex oligosaccharides of mucin in the gut lumen.


A deficiency in arabinogalactan biosynthesis affects Corynebacterium glutamicum mycolate outer membrane stability.
Corynebacterineae is a specific suborder of Gram-positive bacteria that includes Mycobacterium tuberculosis and Corynebacterium glutamicum. The ultrastructure of the cell envelope is very atypical. It is composed of a heteropolymer of peptidoglycan and arabinogalactan (AG) covalently associated to an outer membrane. Five arabinosyltransferases are involved in the biosynthesis of AG in C. glutamicum. AftB catalyzes the transfer of Araf (arabinofuranosyl) onto the arabinan domain of the arabinogalactan to form terminal beta(1 --> 2)-linked Araf residues. Here we show that Delta aftB cells lack half of the arabinogalactan mycoloylation sites but are still able to assemble an outer membrane. In addition, we show that a Delta aftB mutant grown on a rich medium has a perturbed cell envelope and sheds a significant amount of membrane fragments in the external culture medium. These fragments contain mono- and dimycolate of trehalose and PorA/H, the major porin of C. glutamicum, but lack conventional phospholipids that typify the plasma membrane, suggesting that they are derived from the atypical mycolate outer membrane of the cell envelope. This is the first report of outer membrane destabilization in the Corynebacterineae, and it suggests that a strong interaction between the mycolate outer membrane and the underlying polymer is essential for cell envelope integrity. The presence of outer membrane-derived fragments (OMFs) in the external medium of the Delta aftB mutant is also a very promising tool for outer membrane characterization. Indeed, fingerprint analysis of major OMF-associated proteins has already led to the identification of 3 associated mycoloyltransferases and an unknown protein with a C-terminal hydrophobic anchoring domain reminiscent of that found for the S-layer protein PS2 of C. glutamicum.


The use of heparin, bFGF, and VEGF 145 grafted acellular vascular scaffold in small diameter vascular graft.
We aim to test the application of heparin, bFGF, and VEGF 145 grafted acellular vascular scaffold in small diameter vascular graft. The amount of bFGF and VEGF 145 were determined by ELISA. Femoral artery transplantation was performed. Mechanical strength of acellular vascular scaffolds was determined. Angiography was performed for blood vessel patency. Factor VIII and α2-actin expression was detected by immunohistochemistry. bFGF and VEGF 145 had stable release at 60 and 70 days in vitro, and the release rate of VEGF 145 was slightly slower than that of bFGF. After transplantation, 9 months of the vascular patency rate was 100% at 1, 3, and 9 months, and, was up to 90% at 18 months, while the patency rate in group with grafted heparin only at 1-month was 60%, at 3-month was 40%, at 9-month was 15%, and at 18-month was 10%. The blood vessels taken after 18 months had no significant difference in the mechanical properties between the transplanted and the natural vessels. Positive expression of factor VIII and α2-actin was observed. The heparinized and bFGF and VEGF 145 grafted allogeneic vascular acellular scaffolds are preliminarily obtained, which show good biocompatibility and patency and are of great importance for small diameter vascular graft. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 672-679, 2019.


Family therapy with deaf persons: the systemic utilization of an interpreter.
This paper discusses the theory and practice of providing family therapy to families in which there are hearing parents and at least one Deaf child, particularly regarding the optimal utilization of an interpreter. The therapist must be knowledgeable about the psychosocial effects of deafness, the cultural aspects of deafness, and preferably be able to use American Sign Language and Signed English. The therapeutic benefit of utilizing an interpreter extends far beyond simply facilitating communication between each family member whose primary-language is either spoken English or Sign Language. The presence of an interpreter helps the therapist to modify family rules that deny the implications of deafness and prohibit the use of Sign Language, to modify the balance of power in the family, and to encourage participants to exhibit the ego defense mechanisms of projection and transference. The family therapist can utilize those subtle yet profound influences to therapeutic advantage.


A systems-based framework for understanding complex metabolic and cardiovascular disorders.
Common forms of metabolic and cardiovascular diseases involve the interplay of numerous genes as well as important environmental factors. Traditional biochemical and genetic approaches generally attempt to dissect these diseases one gene at a time, for example, by analysis of Mendelian forms or genetically engineered experimental organisms. But, it is also important to understand how the genes interact with each other and the environment, and how these interactions change in disease states. Technological advances, such as the development of expression arrays that allow quantification of all transcript levels in a cell or tissue, have made it feasible to globally monitor molecular phenotypes that underlie disease states. By applying statistical methods, relationships between DNA variation, gene expression patterns, and diseases can be modeled.


Subject, sexuality and biopower: legal defence of soldiers living with HIV and sexual rights in Mexico.
The appeals that 11 service men filed against the Mexican Army in 2007 for unfair dismissal, on the grounds that they were living with HIV, opened an unprecedented chapter in the relationship between sexuality and the judicial system in Mexico, and in the links between biopower and the processes of democratisation and citizenship in the country. In this article, we analyse this process by looking at claimants' discourses as well as those of the Supreme Court judges. We follow three analytic axes: the relationship between biopower and human rights; the paradoxical place of sexuality in this legal process as an element that is both present and absent in legal debates; and the spectre of homosexuality as the implicit undercurrent of this tense discursive event.


FERTILITY SELECTION ON A DISCRETE FLORAL POLYMORPHISM IN CLARKIA (ONAGRACEAE).
This study investigated fertility selection on a flower petal pigmentation polymorphism in Clarkia gracilis ssp. sonomensis. Natural populations are typically composed of nearly 100% spotted-petal plants, although rare populations contain a majority of unspotted plants. I compared fitness values for the two morphs using a simple fertility model to estimate selection for experimental arrays of plants placed into existing populations of different phenotypic frequencies. Both male and female reproductive success were estimated as well as the pattern of mating among phenotypes. Although the separate fitness components varied from no differences to a strong advantage for spotted plants, for every situation the selection calculations predicted an increase in the frequency of the spotted allele. Pollinator behavior and postpollination mechanisms may be responsible for the fitness differences. The apparent inability of the unspotted allele to spread though most natural populations is consistent with its selective disadvantage in this study.


Low-Percentage Ln3+ Doping in a Tetranuclear Lanthanum Polyoxometalate Assembled from [Mo7O24]6- Polyanions Yielding Visible and Near-Infrared Luminescence.
A rare case of low-percentage trivalent lanthanide doping in multinuclear lanthanide polyoxometalates (LnPOMs) was investigated. The [La4(MoO4)(H2O)16(Mo7O24)4]14- polyanion was chosen as the host material for this study. In this polyanion the central [La4(MoO4)]10+ core is coordinated by four heptamolybdate groups as well as 16 water molecules. The tetranuclear lanthanum POM was doped with 5% of Eu3+, Tb3+, Sm3+, Dy3+, Nd3+, Er3+, and Yb3+ (according to synthesis), and the structures and luminescence properties of the x%Ln:LaPOMs were investigated. Additionally a series of tetranuclear lanthanide POMs built from [Mo7O24]6- heptamolybdate polyanions with Eu3+, Tb3+, Sm3+, Dy3+, and Nd3+ instead of La3+ were synthesized, and a detailed analysis revealed that the tetranuclear clusters formed monomers or dimers linked through oxygen bridges. The smaller lanthanide ions, namely, Er3+ and Yb3+, did not form tetranuclear clusters, but instead mononuclear sandwich-type POMs were obtained. The obtained structures were shown to be lanthanide-specific, and not a result of different synthetic/crystallization conditions. The luminescence properties of the x%Ln:LaPOMs were compared with the luminescence properties of the LnPOMs.


Phosphorus and other aspects of CKD-MBD in the conservative management of chronic kidney disease.
As the prevalence of chronic kidney disease (CKD) increases and the population ages, there is an imperative to offer cost effective and patient specific therapeutic options for the management of advanced CKD. In cases where there is a desire to avoid or delay renal replacement therapy, conservative options need to be defined and strategies for delaying the need for renal replacement therapy should be offered. CKD-mineral bone disorders (MBD) refers to the constellation of disturbances in abnormal bone and soft tissue calcification along with abnormalities, in phosphorus, calcium, parathyroid hormone, vitamin D, and FGF-23. CKD-MBD is associated with morbidity and mortality in dialysis patients. Addressing CKD-MBD necessitated understanding phosphorus handling in the intestine and kidney and the ordered process of vascular calcification and uremic osteodystrophy. Decreasing dietary phosphorus intake and absorption is the mainstay of conservative management of CKD-MBD; pharmacologic therapy with binders, vitamin D analogues, and niacin may also be indicated. FGF-23 levels, parathyroid hormone levels, tubular reabsorption of phosphorus, and 24 hour urinary phosphorus can be tracked to trigger and evaluate these interventions. Further research is required to generate an ordered multifaceted approach to CKD-MBD.


The exchange of unesterified cholesterol between human low-density lipoproteins and rat erythrocyte 'ghosts'.
1. The exchange of unesterified cholesterol molecules between rat erythrocyte ;ghosts' and human low-density lipoproteins has been studied under a number of different experimental conditions. 2. The process is pH-dependent, the rate being minimal at about pH5. 3. Cholesterol exchange does not vary greatly with temperature, the rate at 50 degrees being less than twice that at 2 degrees . 4. Large variations in the ionic strength or Ca(2+) concentration of the medium have little effect, but the exchange rate is greatly increased in the presence of a wide range of chemical compounds, e.g. urea, alcohols, acetone, dimethyl sulphoxide and tetra-alkyl-ammonium salts. 5. Acetone and dimethyl sulphoxide have a much greater effect at 37 degrees than at 8-10 degrees . 6. It is proposed that hydrophobic bonding is of great importance in maintaining the structure of ;ghosts' and lipoproteins. 7. The results are discussed in relation to current theories of membrane and lipoprotein structure.


Modified step-cut medial malleolar osteotomy for osteochondral grafting of the talus.
Osteochondral grafting for the treatment of osteochondral lesions of the talus (OLT) usually requires a medial malleolar osteotomy (MMO) to achieve adequate intraarticular exposure. This study describes the technique used and the results obtained using a modified step-cut MMO for osteochondral grafting of talar dome lesions. Eleven feet in ten patients underwent modified step-cut MMO prior to osteochondral grafting for OLT. The patients included three women and seven men with a mean age of 40 (range, 20 to 51) years. Modified step-cut MMO consisted of an oblique osteotomy, which was made at approximately 45 degrees to the transverse plane of the proposed traditional step-cut osteotomy, and a vertical osteotomy to the axilla on the medial tibial plafond. In all patients, modified step-cut MMO provided better perpendicular access to lesions than traditional step-cut osteotomy. In all cases, the osteochondral graft plug was accurately set perpendicular to the defect area, and all ten patients experienced uncomplicated osteotomy healing at a mean 8 weeks postoperatively without loss of reduction or malreduction. Modified step-cut MMO is an excellent, reproducible method for perpendicular access to a talar dome lesion.


Shape assisted fabrication of fluorescent cages of squarate based metal-organic coordination frameworks.
Micronic cage structures of squarate based metal-organic coordination frameworks (MOCFs) have been fabricated for the first time by specific anion selective etching of metal squarate cubes. Time and stoichiometry dependent synthesis and the corresponding microscopic studies have provided mechanistic insight into the cage formation. Furthermore, a non-covalent post-synthetic strategy has been adopted to functionalize the micronic cubes or cages with chromophores rendering the resulting hybrids green fluorescent.


[Cerebrospinal fluid hypotension after brain surgery].
A severe complication, c. s. f. hypotension ( CSFH ), developed in 9 patients after intracranial manipulations for meningioma (4), intracranial aneurysm (3), and subdural hematoma (2). It occurred on the second or third postoperative day and was characterized by rapid development of general cerebral disorders (even to deep loss of consciousness) and aggravation of focal disorders. An important role in the differential diagnosis of the hypotensive and the hypertensive syndromes is attached to lumbar puncture which in cases of CSFH reveals very low c. s. f. pressure or none at all. Effective therapy for the disease includes subarachnoid infusion of up to 50-80 ml of physiological solution through a lumbar puncture and daily intravenous infusions of fluio (2 500-3 000 ml).


Magnetic resonance imaging in sports medicine--an overview.
As more Britons become health conscious and are involved in a variety of sporting events, sports-related injuries are a daily occurrence. Although evaluation of bony abnormalities resulting from acute and chronic sports injury by conventional radiography and bone scintigraphy has been satisfactory, the assessment of soft tissue and tendinous injury is more difficult and imprecise. Due to its superior contrast sensitivity and multiplanar imaging capability, magnetic resonance imaging has already shown great promise in delineating soft-tissue and tendinous abnormalities. In addition, marrow pathology is exquisitely displayed.


Delays in diagnosis and treatment of venous thromboembolism in a developing country setting.
Rapid diagnosis and treatment of deep vein thrombosis and pulmonary thromboembolism reduce mortality and morbidity. The aim of this study is to investigate delays in treatment of deep vein thrombosis and pulmonary thromboembolism and related factor in a developing country. We prospectively investigated 353 patients with diagnosis deep vein thrombosis and/or pulmonary thromboembolism in Urmia, Iran. We recorded dates of symptom onset, initial visit by a clinician, initiation of treatment, and confirmation of diagnosis. We also analyzed relation with some factors. The mean interval from symptoms onset to initiation of treatment was 4.70 days, 89% of this interval was between onset of symptoms to first medical evaluation (mean= 4.19 days). Mean time from onset of symptoms to confirmation of diagnosis was 6.29 days. Of 353 patients with venous thromboembolism 185 (52.4%) visited by a physician within two days of onset of symptoms and 168 (47.6%) patients after two days. Factors that was associated with earlier seeking with p value < 0.05 were pulmonary thromboembolism patients earlier than deep vein thrombosis, higher education, recent surgery, presence of cast, entire leg swelling. There was no association between age, gender, number of symptoms, and presence familial history of venous thromboembolism (all p value > 0.05). The delays time from first visit to final diagnosis was significantly shorter in patients with high probability score. Most patients with venous thromboembolism received anti-coagulation and diagnosis with delay. The main cause of delay is related to patient's delays. There is a need to improve people awareness about venous thromboembolism and to develop strategies to reduce delays.


Exanthema and enanthema in graft versus host disease (GVHD).
Two cases of graft versus host disease (GVHD) were reported. Case 1: A 74-year-old man noticed erythematous rash with high fever in fourteen days after blood transfusion. Skin rash spread gradually and resulted in toxic epidermal necrolysis (TEN) in accompany with diarrhea, liver dysfunction and pancytopenia. Case 2: A 24-year-old man with acute lymphocytic leukemia treated with allogeneic bone marrow transplantation, developed macular erythema diffusely and he had received transfusion of peripheral buffy coat cells from his brother. Histological findings revealed eosinophilic necrotic keratinocytes and infiltrating cells which consisted of CD4 and CD8(+) T cells. The both cases were diagnosed as GVHD caused by blood transfusion, though in case 1, differentiation from toxic eruption was needed. We described clinical and histopathological findings of the cutaneous manifestations of GVHD and distinction from some cutaneous lesions caused by drug toxicity and collagen disease.


A malignant retroperitoneal mass--a rare presentation of recurrent thymoma.
A 60-year-old man presented with a suspected retroperitoneal mass, after primarily resected thymoma (type B1/B2, Masaoke stage 1). A germ cell tumour was excluded and a diagnostic biopsy was performed. The mass appeared to be a local recurrence of the primary thymoma, for example, a droplet metastasis, progressed to type B3.


Ownership and usage of mosquito nets after four years of large-scale free distribution in Papua New Guinea.
Papua New Guinea (PNG) is a highly malaria endemic country in the South-West Pacific with a population of approximately 6.6 million (2009). In 2004, the country intensified its malaria control activities with support from the Global Fund. With the aim of achieving 80% ownership and usage, a country-wide campaign distributed two million free long-lasting insecticide-treated nets (LLINs). In order to evaluate outcomes of the campaign against programme targets, a country-wide household survey based on stratified multi-stage random sampling was carried out in 17 of the 20 provinces after the campaign in 2008/09. In addition, a before-after assessment was carried out in six purposively selected sentinel sites. A structured questionnaire was administered to the heads of sampled households to elicit net ownership and usage information. After the campaign, 64.6% of households owned a LLIN, 80.1% any type of mosquito net. Overall usage by household members amounted to 32.5% for LLINs and 44.3% for nets in general. Amongst children under five years, 39.5% used a LLIN and 51.8% any type of net, whereas 41.3% of pregnant women used a LLIN and 56.1% any net. Accessibility of villages was the key determinant of net ownership, while usage was mainly determined by ownership. Most (99.5%) of the household members who did not sleep under a net did not have access to a (unused) net in their household. In the sentinel sites, LLIN ownership increased from 9.4% to 88.7%, ownership of any net from 52.7% to 94.1%. Usage of LLINs increased from 5.5% to 55.1%, usage of any net from 37.3% to 66.7%. Among children under five years, usage of LLINs and of nets in general increased from 8.2% to 67.0% and from 44.6% to 76.1%, respectively (all p ≤ 0.001). While a single round of free distribution of LLINs significantly increased net ownership, an insufficient number of nets coupled with a heterogeneous distribution led to overall low usage rates. Programme targets were missed mainly as a result of the distribution mechanism itself and operational constraints in this very challenging setting.


Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System.
Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.


Protocol for a national cohort study to explore the long-term clinical and patient-reported outcomes and cost-effectiveness of implant-based and autologous breast reconstruction after mastectomy for breast cancer: the brighter study.
Breast reconstruction (BR) is offered to improve quality of life for women with breast cancer undergoing mastectomy. As most women will be long-term breast cancer survivors, high-quality information regarding the long-term outcomes of different BR procedures is essential to support informed decision-making. As different techniques vary considerably in cost, policymakers also require high-quality cost-effectiveness evidence to inform care. The Brighter study aims to explore the long-term clinical and patient-reported outcomes (PROs) of implant-based and autologous BR and use health economic modelling to compare the long-term cost-effectiveness of different reconstructive techniques. Women undergoing mastectomy and/or BR following a diagnosis of breast cancer between 1 January 2008 and 31 March 2009 will be identified from hospital episode statistics (HES). Surviving women will be contacted and invited to complete validated PRO measures including the BREAST-Q, EQ-5D-5L and ICECAP-A, or opt out of having their data included in the HES analysis. Long-term clinical outcomes will be explored using HES data. The primary outcome will be rates of revisional surgery between implant-based and autologous procedures. Secondary outcomes will include rates of secondary reconstruction and reconstruction failure. The long-term PROs of implant-based and autologous reconstruction will be compared using BREAST-Q, EQ-5D-5L and ICECAP-A scores. Multivariable regression will be used to examine the relationship between long-term outcomes, patient comorbidities, sociodemographic and treatment factors. A Markov model will be developed using HES and PRO data and published literature to compare the relative long-term cost-effectiveness of implant-based and autologous BR. The Brighter study has been approved by the South-West -Central Bristol Research Ethics Committee (20/SW/0020), and the Confidentiality Advisory Group (20/CAG/0021). Results will be published in peer-reviewed journals and presented at national meetings. We will work with the professional associations, charities and patient groups to disseminate the results.


Use of serum creatine kinase MM isoforms for predicting the progression of left ventricular dilation in patients with hypertrophic cardiomyopathy.
Serum creatine kinase (CK) isoforms were examined to detect the progression of left ventricular (LV) enlargement with reduced motion, resembling dilated cardiomyopathy (DCM), in hypertrophic cardiomyopathy (HCM). Changes in LV indices were determined annually by echocardiography in 51 patients until serum measurements (first follow-up period, 6.5 +/- 2.2 years). Serum creatine isoforms (CKMM1, CKMM2 and CKMM3) were measured with high-voltage electrophoresis in 35 of these patients from 1991 to 1992, and the data for these latter patients are reported here. Serum total CK, CKMB, lactate dehydrogenase and its isoenzyme LDH1 were also measured. The changes in LV indices were further monitored until January, 1995 (second follow-up). During the 2 follow-up periods, the patients in the on-going group showed a reduction in the LV ejection fraction (LVEF) to < 55% with LV end-diastolic dimension (LVDd) < 55 mm, and those in the DCM-like group showed a reduction in LVEF to < 55% and an increase in LVDd to > 55 mm. During the first follow-up period, LVEF and LVDd remained at > or = 55% and < 55 mm, respectively, in 26 patients (nonprogressive-disease group), while 3 patients entered the on-going group and 6 entered the DCM-like group. The CKMM3/CKMM1 ratios in the on-going and DCM-like groups were significantly higher than those in the control and nonprogressive-disease groups. The CKMM3/CKMM1 ratio was significantly correlated with the annual rate of change for the LV end-systolic dimension (LVDs), LVDd, and LVEF, with the closest correlation observed for the annual change in LVDs. Moreover, 5 patients in the nonprogressive-disease group with elevation of the CKMM3/CKMM1 ratio to > + 2SD above the mean for the controls had an elevated annual change in LVDs within +/- 1SD of the mean in the DCM-like group. These results indicate that the ratio of CKMM3 to CKMM1 can be used to predict the progression of LV enlargement in HCM.


Synchronous primary adenocarcinoma and ancient schwannoma in the colon: an unusual case report.
Gastrointestinal schwannomas are uncommon stromal tumors of the intestinal tract and colon schwannomas are extremely rare. We report a rare case of ascending colon schwannoma with associated synchronous adenocarcinoma of the sigmoid colon. A 68-year-old man presented with a 20-day history of bleeding per rectum. Colonoscopy revealed a mass of 4.2 cm in diameter with endoluminal protrusion in the sigmoid colon and a second submucosal tumor in the ascending colon. Surgical intervention was suggested and ileo-hemicolectomy was done. Microscopically, the submucosal tumor of 4 cm in diameter showed features of schwannoma with degenerative change (ancient schwannoma). Lesional cells were positive for S100p and negative for actin, desmin, CD34, CD117, and pankeratin. The mass showed features of an invasive moderately differentiated adenocarcinoma. Colon schwannoma is a rare submucosal tumor, and the incidental occurrence with adenocarcinoma has not been well described in the literature.


Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys.
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys (n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.


Predicting long-term nursing home transfer from MI choice waiver program.
This study aimed to identify characteristics of elderly participants in the Michigan Home and Community-Based Waiver Program that are associated with high risk of long-term nursing home (LT-NH) placement. We identified 8172 waiver clients aged 65 and older during 10/1/2010-9/30/2014. A proportional cause-specific hazards regression model was used to analyze risk factors of waiver elderly for LT-NH placement. Waiver elderly participants who were white (HR (white vs. black): 2.76, with 95% CI (1.91, 4.00); HR (white vs. other races): 1.77, with 95% CI (1.05, 2.97)), had a history of long-term care use (HR: 1.42, 95% CI (1.14, 1.76)), mental disorders (HR: 1.51, 95% CI (1.23, 1.86)), bathing dependency (HR: 1.43, 95% CI (1.07, 1.89)), and finance management dependency (HR: 1.73, 95% CI (1.15, 2.60)) had greater hazards of LT-NH placement. Our study can be useful for policy makers to develop relevant support to reduce LT-NH placement.


Indications for and results with the Swanson distal ulnar prosthesis.
Classically, wrist synovectomy, when the distal radioulnar joint is involved, includes excision of the distal ulna (the classical Darrach procedure). Orthopedists and rheumatologists are well aware of the propensity for extensor tendon rupture, particularly of the ring and little finger, in this area. Dr. Alfred Swanson has presented his results with a silastic interposition to substitute for the excision of the distal ulna. This paper presents a surgical technic, indications, and results in five cases of rheumatoid arthritis in which wrist synovectomy and repair of extensor tendon ruptures were done as appropriate. This distal ulnar prosthesis is recommended for routine use in wrist synovectomy when excision of the distal ulna is performed.


Morphological Analysis of Bronchial Arteries and Variants with Computed Tomography Angiography.
The aim of our study was to determine the prevalence of anatomical variants of bronchial arteries using computed tomographic angiography in a population of northeastern Mexico. An observational, transversal, descriptive, comparative, retrospective study was performed using 139 imaging studies of Mexican patients in which we evaluated the following parameters from the left and right bronchial arteries: artery origin, branching pattern, arterial ostium, vertebral level of origin, diameter, and mediastinal trajectory. The anatomies of the bronchial arteries were similar in both genders, except distribution for vertebral origin level (p 0.006) and the diameter (p 0.013). Left and right arteries were similar, except for the mediastinal trajectory in reference to the esophagus (p < 0.001) as well as the arterial diameter (p < 0.001) and lumen diameter.


Adjuvant therapy in different risk-groups of patients with superficial bladder cancer.
We assessed and compared the outcomes of two different courses of adjuvant therapy to patients with superficial bladder TCC. The study included 142 patients (28 women and 114 men with a median age of 58.5 years) with newly diagnosed bladder transitional cell carcinoma (TCC), who underwent transurethral resection of bladder tumor (TURBT) between October 2002 and October 2003. Before surgery patients underwent routine examination, including measurement of tPSA level and transrectal ultrasound sonography (TRUS). In 26 (18.3%) patients with considerably enlarged prostate and LUTS we simultaneously performed TURBT and transurethral resection of the prostate (TURP). Pathological findings showed pTa stage in 20 (14.1%), pT1G1-2 in 99 (69.7%), pT1G3 in 15 (10.6%) and pTis in 3 (2.1%) cases; we additionally examined prostate specimens after TURP. The main criteria for adjuvant treatment were: grade, number and location of the tumor in the bladder The group of patients (group A) with G3 and multicentric lesions, localized at the lower third of the bladder, underwent BCG-therapy according the conventional schedule (60 patients, 42.3%). In group B (82 patients, 57.7%) patients underwent local chemotherapy (Thiotepa 80 mg p/week or Doxorubicin 50 mg p/week), started within 24 hours after operation. A second-look TURBT was performed within 6 weeks of treatment course in both groups. The morphological records of surgery were reviewed, compared with the initial findings and analysed statistically. Recurrence rate in groups A and B was 18.3% (11 patients) and 25.6% (21 patients), respectively (with common level 22.5%) (p=0.04). Three (5.0%) patients of group A and five (6.1%) of group B withdrew consent. We observed recurrent low-grade pTa tumours in 4 patients (36.4%) and 8 patients (38.1%) respectively in group A and B (p<0.03) and pT1 G1-2 tumours in 5 patients (45.5%) and 8 patients (38.1%) respectively in group A and B (p<0.005). We observed pT1G3 in two (18.2%) cases of group A, and in two (9.5%) cases of group B. In addition, two (9.5%) patients of B group had T2G2 lesions. Adjuvant therapy was continued in all patients, except four patients with G3 and two patients with T2 stage who underwent more aggressive treatment (4 cystectomies and 2 external beam radiotherapy). We switched 16 patients in group B with recurrent cancer to BCG treatment. Nobody of TURP-operated patients had recurrence in the distal part of urethra, and toxicity level of TURP-operated patients was not worse than in the whole patients cohort (not more than grade II). BCG adjuvant therapy demonstrated good results in the treatment of the recurrence of superficial TCC. However, in patients with low recurrence risk we used chemotherapy successfully. A second-look TURBT within 6 weeks after the initial surgery provided important prognostic information. Patients with T1G3 tumors, being at high risk of residual, or even invasive, cancer, could be offered definitive therapy within a 1-year period. Patients who underwent simultaneous TURP for relief of LUTS did not show cancer recurrences in the operated area or an higher toxicity of adjuvant treatment.


Non-Amyloid-β Component of Human α-Synuclein Oligomers Induces Formation of New Aβ Oligomers: Insight into the Mechanisms That Link Parkinson's and Alzheimer's Diseases.
Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), of which their major component is the non-amyloid-β component (NAC) of α-synuclein (AS). Clinical studies have identified a link between PD and Alzheimer's disease (AD), but the question of why PD patients are at risk to develop various types of dementia, such as AD, is still elusive. In vivo studies have shown that Aβ can act as a seed for NAC/AS aggregation, promoting NAC/AS aggregation and thus contributing to the etiology of PD. However, the mechanisms by which NAC/AS oligomers interact with Aβ oligomers are still elusive. This work presents the interactions between NAC oligomers and Aβ oligomers at atomic resolution by applying extensive molecular dynamics simulations for an ensemble of cross-seeded NAC-Aβ(1-42) oligomers. The main conclusions of this study are as follows: first, the cross-seeded NAC-Aβ(1-42) oligomers represent polymorphic states, yet NAC oligomers prefer to interact with Aβ(1-42) oligomers to form double-layer over single-layer conformations due to electrostatic/hydrophobic interactions; second, among the single-layer conformations, the NAC oligomers induce formation of new β-strands in Aβ(1-42) oligomers, thus leading to new Aβ oligomer structures; and third, NAC oligomers stabilize the cross-β structure of Aβ oligomers, i.e., yielding compact Aβ fibril-like structures.


The right to be treated against her will.
... My sister's inconsistent and intermittent treatment over the past eight years is largely a result of her own indecision and the inconsistencies of her abnormal mental state. The professionals who might have taken control of the situation as her health and functioning deteriorated have not done so and I must presume that they believe they cannot do so. I do not think her case is unique. There are many more people living in the community who are severely ill and are being deprived of treatment they need.


The current training for non‑echocardiographers in University Hospital Hradec Králové.
Emergency echocardiography is a reproducible method providing clinically significant information during the process of primary assessment of the acute cardiovascular diseases. The main aim of the course is implementation of the emergency echocardiography by non-cardiologist is the standardization of the procedure, structured training system and agreement on the competences. The article summaries the current training for non-echocardiographers in University Hospital Hradec Králové.


Changes in neuronal activity of the inferior colliculus in rat after temporal inactivation of the auditory cortex.
The role of cortico-tectal pathways in auditory signal processing was studied in anesthetized rats by comparing the extracellular single unit activity in the inferior colliculus (IC) before and after functional ablation of the auditory cortex (AC) by tetrodotoxin (TTX). The responses of several IC neurons to sound stimuli were simultaneously recorded with a 16-channel electrode probe introduced into the IC. Click-evoked middle latency responses (MLR) recorded from the AC were suppressed for several hours after TTX injection. During AC inactivation the firing rate of IC neurons increased (40 % of neurons), decreased (44 %) or did not change (16 %) in comparison with control conditions. In several IC neurons, TTX injection resulted in alterations in the shape of the rate-level functions. Response thresholds, tuning properties and the type of discharge pattern of IC neurons were not altered during AC inactivation. However, in one-third of the neurons, the initial part of the response was less altered than the later, sustained part. In two-thirds of neuronal pairs, functional decortication resulted in a change in the cross-correlation coefficient. The results reveal the complex changes that appear in IC neuronal activity after functional ablation of the ipsilateral auditory cortex.


Impacts of rapeseed dregs on Cd availability in contaminated acid soil and Cd translocation and accumulation in rice plants.
The objective of the present study was to investigate the effects of rapeseed dregs (RSD, a commonly organic fertilizer in rural China) at application rates of 0, 0.75, 1.5, and 3.0 % on Cd availability in soil and its accumulation in rice plants (Oryza sativa L., Xiangwanxian 12#, and Weiyou 46#) by means of a pot experiment. The results showed that application of RSD resulted in a sharp decrease in the soil TCLP-extractable Cd content. However, the soil TCLP-extractable Cd content in amended soil gradually increased during the rice growing period. Application of RSD significantly increased Cd transport from root to shoot and the amount of Cd accumulated in the aerial part. RSD was an effective organic additive for increasing rice grain yield, but total Cd content in rice grain was also increased. At an application rate of 1.5-3.0 % RSD, the total Cd content in Weiyou 46# brown rice was 0.27-0.31 mg kg-1, which exceeded the standard safe limit (0.2 mg kg-1) and was also higher than that of Xiangwanxian 12# (0.04-0.14 mg kg-1). Therefore, Weiyou 46# had a higher dietary risk than Xiangwanxian 12# with RSD application. We do not recommend planting Weiyou 46# and applying more than 0.75 % RSD in Cd-contaminated paddy fields.


Genotoxicity studies on the removal of a direct textile dye by a fungal strain, in vivo, using micronucleus and RAPD-PCR techniques on male rats.
The genotoxicity of the azo dye 'Direct Violet' and the removal of this dye by Aspergillus niger strain at different conditions have been investigated in male rats. Two genotoxicity techniques, namely bone marrow micronucleus assay and RAPD fingerprinting pattern, were used in this study for the direct dye and its removal by the fungal strain. Sixty male rats were divided into six treatment groups including a control group and other groups which were exposed for 2 or 8 weeks to Direct Violet dye, Direct Violet dye treated with A. niger at pH 2 or pH 9 or without agitation and acrylamide (30 mg/kg b.w.). A potent dose-dependent response was observed following oral gavage of the dye up to 1000 mg kg(-1), after which significant toxicity to the erythroid compartment was observed. Acrylamide and Direct Violet treatments increased the number of micronucleated polychromatic erythrocytes (MnPCEs) with respect to the controls. This increase was statistically significant in the two time intervals (2 and 8 weeks treatment, P < 0.0001). Fungi treatments at pH 2 and without agitation were able to reduce the number of MnPCEs induced by Direct Violet administration in all duration groups. Fungi treatment at pH 9 was only able to inhibit the genotoxicity of Direct Violet after 8 weeks treatment. The RAPD fingerprinting pattern indicated that most DNA of the samples treated with dye alone or acrylamide revealed polymorphic bands including the appearance and disappearance of the bands, which did not appear in the DNA samples of normal or fungi protected rats. The implications of these findings for the health and safety of occupationally exposed workers are discussed.


Facile synthesis of 3D hierarchical micro-/nanostructures in capillaries for efficient capture of circulating tumor cells.
The efficient capture of rare circulating tumor cells (CTCs) with high viability is of great importance in cancer diagnosis. The integration of three-dimensional (3D) nanobiointerfaces with capillary flow channel platforms can efficiently improve CTC capture performance by providing abundant binding sites and increasing the likelihood of contact as samples flow through the microchannels. However, due to the complex preparation processes, facile synthesis of nanostructures for use as substrates in flow channels for biomedical applications is still challenging. To reduce the encapsulation steps in the fabricating of nanostructured flow channel devices, we chose the enclosed glass capillaries as flow channels and accomplished all the experiments in the microchannels, including 3D nanostructure synthesis, surface modification and capture/release of CTCs. In this work, we constructed a novel 3D Zn(OH)F/ZnO nanoforest array in capillaries for CTC isolation via a facile microfluidic wet chemistry method. Because of the abundant binding sites of the 3D Zn(OH)F/ZnO nanoforest array, the capture efficiency was remarkably enhanced compared with that of vertical nanowires (90.3% vs 69.1%). In addition, a high release efficiency and cell viability of released cells were achieved by grafting poly(N-isopropylacrylamide) (PNIPPAm). These results may provide evidence for a novel method to fabricate hierarchical 3D substrates with a combination of biomolecule recognition and topographical interaction for biomedical applications.


Characterization of RNA strand displacement synthesis by Moloney murine leukemia virus reverse transcriptase.
The RNase H activity of reverse transcriptase (RT) is presumably required to cleave the RNA genome following minus strand synthesis to free the DNA for use as a template during plus strand synthesis. However, since RNA degradation by RNase H appears to generate RNA fragments too large to spontaneously dissociate from the minus strand, we have investigated the possibility that RNA displacement by RT during plus strand synthesis contributes to the removal of RNA fragments. By using an RNase H- mutant of Moloney murine leukemia virus (M-MuLV) RT, we demonstrate that the polymerase can displace long regions of RNA in hybrid duplex with DNA but that this activity is approximately 5-fold slower than DNA displacement and 20-fold slower than non-displacement synthesis. Furthermore, we find that although certain hybrid sequences seem nearly refractory to the initiation of RNA displacement, the same sequences may not significantly impede synthesis when preceded by a single-stranded gap. We find that the rate of RNA displacement synthesis by wild-type M-MuLV RT is significantly greater than that of the RNase H- RT but remains less than the rate of non-displacement synthesis. M-MuLV nucleocapsid protein increases the rates of RNA and DNA displacement synthesis approximately 2-fold, and this activity appears to require the zinc finger domain.


SRPIN340 protects heart muscle from oxidative damage via SRPK1/2 inhibition-mediated AKT activation.
SRPIN340, a selective serine-arginine protein kinase 1/2 (SRPK1/2) inhibitor, has been shown to have antiviral and anti-angiogenesis effects. However, its role in the heart is unknown. The present study explored the role of SRPIN340 in myocardial protection and the related mechanisms. During challenge with H2O2, cardiomyocytes (CMs) pretreated with SRPIN340 showed strikingly more injury tolerance, which was manifested as reduced lactate dehydrogenase (LDH) release and lower apoptotic index. Further research showed that SRPIN340 activated AKT under basal conditions, and AKT inhibition abolished the protective effects of SRPIN340 treatment during H2O2 stress. The protective effect of SRPIN340 was also demonstrated in perfused rat hearts subjected to ischemia/reperfusion (I/R). Collectively, our results reveal the beneficial effects of SRPIN340 against H2O2-induced oxidative damage in CMs and I/R-induced injury in a Langendorff heart model, supporting a potential application of SRPIN340 in the clinically relevant context of reperfusion. The effectiveness of SRPIN340 may be attributed to AKT signal activation.


Pneumonia in the elderly: a review.
Elderly persons are at increased risk of acquiring pneumonia. Morbidity and mortality rates from pneumonia are also higher. Clinical manifestations of pneumonia in the elderly are frequently very subtle; however, a high index of suspicion will induce the physician to obtain a chest roentgenogram. A new lung infiltrate will confirm the diagnosis. Although the Gram's stain of a sputum smear is most helpful in the initial selection of a specific antibiotic, a good quality sputum is not usually available in the elderly, and empiric therapy reduces the morbidity and mortality from pneumonia.


Early Postoperative Results in Robotic-Arm-Assisted Total Knee Replacement versus Conventional Technique: First Latin American Experience.
Early results with robotic-arm-assisted total knee arthroplasty (TKA) are encouraging; nevertheless, literature might be unrepresentative, as it comes mostly from American, European, and Asian countries. There is limited experience and no comparative clinical reports in Latin America, a region of mainly low- and middle-income countries with limited access to these promising technologies. This study aims to compare the early postoperative results of the first Latin American experience with robotic-arm-assisted TKA versus conventional TKA. A cohort study was performed, including 181 consecutive patients (195 knees) with advanced symptomatic knee osteoarthritis (OA) undergoing primary TKA between March 2016 and October 2019. The cohort included 111 consecutive patients (123 knees) undergoing conventional TKA, followed by 70 consecutive patients (72 knees) undergoing robotic-arm-assisted TKA. The same surgical team (surgeon 1 and surgeon 2) performed all procedures. Patients with previous osteotomy, posttraumatic OA, and revision components were not considered. The same anesthetic and rehabilitation protocol was followed. The investigated clinical outcomes (for the first 60 postoperative days) were: surgical tourniquet time, time to home discharge, time to ambulation, postoperative daily pain (Visual Analog Scale), opioid use, range of motion, blood loss, complications, and postoperative mechanical axis. The early clinical postoperative results of this first Latin American comparative experience of robotic-arm-assisted TKA versus conventional technique showed lower opioids requirements and faster functional recovery of ambulation in those patients operated with the robotic system; nevertheless, surgical times were higher, without differences in total postoperative complications and other clinical outcomes.


Spread of Quadratus Lumborum Block to the Paravertebral Space Via Intramuscular Injection: A Volunteer Study.
Several types of quadratus lumborum block (QLB) are used for postoperative analgesia and are believed to be effective against both somatic and visceral pain via a local anesthetic (LA) effect in the paravertebral space (PVS). However, it remains unclear whether all QLB techniques result in LA spread into the PVS. We hypothesized that LA administered via intramuscular QLB would spread into the paravertebral space and investigated the spread and sensory block area of LA in intramuscular QLB. This volunteer study included 5 healthy men and 1 woman, with no previous medical history. Intramuscular QLB and lateral transversus abdominis plane block were performed under real-time ultrasound guidance for comparison of sensory deprivation range. Two days later, the same procedure was performed on the contralateral side of the body. The spread of LA via intramuscular QLB spread to the PVS was assessed 1 hour after the first injections using magnetic resonance imaging. Sensory perception was also evaluated by the pinprick test at 90 minutes after injection. In total, we performed 11 intramuscular QLBs and 11 lateral transversus abdominis plane blocks. Magnetic resonance imaging showed that LA did not spread into the PVS after ultrasound-guided intramuscular QLB. The analgesic area corresponded to the side of the body that was ipsilateral to the block. Ultrasound-guided intramuscular QLBs are not clinically useful for procedures requiring LA spread into the PVS but do result in an ipsilateral analgesic effect in healthy volunteers. This study was registered at University Hospital Medical Information Network Clinical Trials Registry, UMIN 000019149.