A framework for managing runoff and pollution in the rural landscape using a Catchment Systems Engineering approach.
Intense farming plays a key role in increasing local scale runoff and erosion rates, resulting in water quality issues and flooding problems. There is potential for agricultural management to become a major part of improved strategies for controlling runoff. Here, a Catchment Systems Engineering (CSE) approach has been explored to solve the above problem. CSE is an interventionist approach to altering the catchment scale runoff regime through the manipulation of hydrological flow pathways throughout the catchment. By targeting hydrological flow pathways at source, such as overland flow, field drain and ditch function, a significant component of the runoff generation can be managed in turn reducing soil nutrient losses. The Belford catchment (5.7 km(2)) is a catchment scale study for which a CSE approach has been used to tackle a number of environmental issues. A variety of Runoff Attenuation Features (RAFs) have been implemented throughout the catchment to address diffuse pollution and flooding issues. The RAFs include bunds disconnecting flow pathways, diversion structures in ditches to spill and store high flows, large wood debris structure within the channel, and riparian zone management. Here a framework for applying a CSE approach to the catchment is shown in a step by step guide to implementing mitigation measures in the Belford Burn catchment. The framework is based around engagement with catchment stakeholders and uses evidence arising from field science. Using the framework, the flooding issue has been addressed at the catchment scale by altering the runoff regime. Initial findings suggest that RAFs have functioned as designed to reduce/attenuate runoff locally. However, evidence suggested that some RAFs needed modification and new RAFs be created to address diffuse pollution issues during storm events. Initial findings from these modified RAFs are showing improvements in sediment trapping capacities and reductions in phosphorus, nitrate and suspended sediment losses during storm events.


Halitosis and Helicobacter pylori: a possible relationship.
With the aim of investigating a possible relationship between "objective" halitosis (established by sulfide levels in the breath) and Helicobacter pylori, we performed a study in 58 dyspeptic patients reported to suffer from "bad breath." Furthermore, we evaluated the effects on halitosis of eradication therapy (only for H. pylori-positive patients) and chlorhexidine antiseptic mouth rinses (in all patients). Sulfide compound assay indicated objective halitosis in 52/58 patients, 30 of whom were positive and 22 negative for H. pylori. In 19/30 eradication by double therapy provoked a decrease to below the cutoff value of sulfide levels in 15. In the other 11 of the 30 subjects, in whom H. pylori positivity persisted, halitosis parameters did not change. Chlorexidine reduced sulfides to below the cutoff value in 16/22 H. pylori-negative patients, but did not provoke any change in the 11 unsuccessfully treated H. pylori-positive subjects. In these, objective halitosis disappeared only after a successful eradication by triple therapy (9/11). Our results show a possible association between halitosis and H. pylori since bacterial eradication may resolve the symptom. Antiseptic mouthwashes may be effective only in absence of H. pylori, when halitosis may be due to oral putrefactive microbial activity. In a small number of subjects the cause and treatment of halitosis need to be clarified.


Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis.
While increased concentrations of C-reactive protein (CRP) are associated with increased vascular risk, little information is available describing genetic determinants of this effect. In a large prospective cohort of apparently healthy men, we found plasma CRP concentrations to be significantly reduced among carriers of a 1059G/C polymorphism in the human CRP gene (GC or CC) as compared with non-carriers (GG). However, the polymorphism examined was not significantly associated with risk of arterial thrombosis despite the fact that CRP concentrations are a potent independent predictor of future vascular events in this cohort. These data suggest that genetic and environmental determinants each importantly contribute to the vascular risk associated with inflammation.


Pseudorabies virus envelope glycoprotein gI influences both neurotropism and virulence during infection of the rat visual system.
We previously demonstrated that intraocular injections of virulent and attenuated strains of pseudorabies virus (PRV) produce transneuronal infection of functionally distinct central visual circuits in the rat. The virulent Becker strain of PRV induces two temporally separated waves of infection that ultimately target all known retinorecipient neurons; the attenuated Bartha strain only infects a functionally distinct subset of these neurons. In this study, we demonstrate that deletion of a single viral gene encoding glycoprotein gI is sufficient to reproduce both the novel pattern of infectivity and the reduced neurovirulence of the Bartha strain of PRV. Glycoprotein gIII, a major viral membrane protein required for efficient adsorption of virus in cell culture, has no obvious role in determining the pattern of neuronal infectivity, but appears to function with gI to influence neurovirulence. These data suggest that neuroinvasiveness and virulence are the products of an interaction of viral envelope glycoproteins with as yet unidentified cellular receptors.


[Tpeak-Tend interval and risk of cardiac events in patients with Brugada syndrome].
To evaluate the possible association between Tpeak-Tend (Tp-e) interval in surface standard ECG and cardiac events in patients with Brugada syndrome (BrS). Tp-e interval in surface standard ECG was compared between BrS patients (n = 23, all males) and paroxysmal supraventricular tachycardia (PSVT) patients (n = 20, all males) as well as between BrS patients with (n = 16) or without (n = 7) cardiac events. There was significant difference in Tp-e interval between BrS patients and PSVT patients [(109.57 +/- 22.86) ms vs. (88.50 +/- 13.08) ms, P < 0.05]. Tp-e interval was also significantly longer in BrS patients with cardiac events (syncope, clinical ventricular fibrillation and induced VF during electrophysiological study) than BrS patients without cardiac events [(118.12 +/- 20.40) ms vs. (90.00 +/- 15.27) ms, P < 0.05] while Tp-e interval was similar between BrS patients without cardiac events and PSVT patients (P > 0.05). The prolongation of Tp-e (> or = 120 ms) was associated with higher cardiac events in BrS patients.


Trust, moral responsibility, the self, and well-ordered societies: the importance of basic philosophical concepts for clinical ethics.
Although the work of clinical ethics is intensely practical, it employs and presumes philosophical concepts from the central branches of philosophy, including metaphysics, epistemology, ethics, and political philosophy. This essay introduces this issue in the Journal on clinical ethics by considering how the papers and book reviews included in it illuminate four such concepts: trust, moral responsibility, the self and well-ordered societies.


Leptospira icterohaemorrhagiae infection presenting as acute renal failure.
The features of leptospiral infection should be sought in all cases of acute renal failure since management depends on the recognition of the clinical syndrome and serological confirmation is usually delayed. Hepatic and renal involvement is usual but renal failure without significant derangement of liver function is described.


A reappraisal of vector control strategies for babesiosis.
This review suggests that we are on the threshold of a new epoch in the control of ticks and the diseases transmitted by them. Ecological studies of parasitic and non-parasitic stages of the tick life cycle have shown how strategic dipping can lead to effective control of Boophilus ticks. However, this approach can lead to drastic reduction in tick populations which may favour the development of enzootic instability. On the other hand, mathematical models and field studies indicate that we can eradicate babesiosis without eradicating the tick vector. As no well-established vaccine exists for babesiosis or its vectors, it is important to anticipate the possible effects of low or fluctuating populations of ticks caused by strategic control programmes. Under these conditions, it is probable that babesiosis will disappear before the tick vector does. Prudent use of tick bionomic data from several centres of field research, as well as models to analyse these data, should accelerate the latter process. Epidemiological models should be included in the analysis of babesiosis in areas that run the risk of converting from stable zones to unstable zones due to strategic dipping. These observations and projections underscore the value of integration of traditional and modern techniques in the control of babesiosis and other vector-borne diseases.


Efficacy of the Technologically Processed Antibodies to the Brain-Specific S100 Protein in a Rat Model of Hemorrhagic Stroke.
We studied the ability of technologically processed antibodies to the brain-specific S100 protein (drug Prospekta) to reduce the brain lesion area, neurological disorders, and mortality in a rat model of hemorrhagic stroke. Technologically processed antibodies to S100 exerted a positive effect on all these parameters (brain lesion area, survival rate, neurological status according to the Menzies scale, and proportion of contralateral turns). This allows us to recommend further research into the spectrum of pharmacological activity and the mechanism of action of technologically processed antibodies to S100 in order to expand the indications for their use after the necessary clinical trials.


Birth weight was associated with maternal exposure to intimate partner violence during pregnancy in southern Ethiopia: A prospective cohort study.
Birth weight is defined as the first weight of the newborn, ideally measured soon after birth. A recent Ethiopian survey estimated that 48% of births took place in health facilities. Data for women exposed to intimate partner violence (IPV) may be lacking in official statistics because these women may prefer to deliver at home, where data from non-institutional births, including reporting of birth weights, are not routinely recorded. The aim of this study was to investigate the association between maternal exposure to IPV during pregnancy and birth weight in a community in the Wondo Genet district of southern Ethiopia. We carried out a community-based prospective cohort study from February to December 2017. We followed up with 505 pregnant women and their newborns until after delivery. An interview about partner violence was done during pregnancy at home when enrolled. Field assistants who visited the homes measured the birth weight of each baby in grams. Twins and late birth weight measurements were excluded. Factors associated with birth weight were assessed by multiple linear regression. Birth weight was assessed within 48 h for 477 (94.5%) newborns and between 48 and 72 h for an additional 28 (5.5%). There were 365 (72.3%) institutional deliveries. In an adjusted regression analysis (IPV adjusted for socio-economic status), birth weight was 203 g lower (B -203 95% CI -320 to -87) among newborns of women exposed to IPV than among the unexposed. Birth weight was also lower in girls than in boys, in newborns delivered at home rather than in a health facility, and in babies with a younger gestational age. Maternal exposure to IPV during pregnancy was associated with lower baby birth weights. Antenatal clinics should consider routinely identifying IPV-exposed women, and identifying babies with lower birth weights at home is an important indicator.


The Attitudes of Polish Women towards Breastfeeding Based on the Iowa Infant Feeding Attitude Scale (IIFAS).
The Iowa Infant Feeding Attitude Scale (IIFAS), which is used for the assessment of attitudes towards breastfeeding, has been found to be reliable and valid in a number of countries, but has not yet been psychometrically tested in Polish women. The purpose of the study was to report on the cultural adaptation of the IIFAS to Polish settings and on its validation, to evaluate the breastfeeding attitudes in Polish women who recently gave birth, and to identify the determinants of these attitudes. The study was performed in a group of 401 women in their first postpartum days. Cronbach's α for the scale was 0.725. Discriminative power coefficients of all questionnaire items were higher than 0.2. Subscales were strongly correlated with the total score, with a correlation coefficient of 0.803 for the "favorable toward breastfeeding" subscale (p < 0.001), and 0.803 for the "favorable toward formula feeding" subscale (p < 0.05). For the item "A mother who occasionally drinks alcohol should not breastfeed her baby", the factor loading did not reach the criterion value, and so the item was not included in further analyses. The mean IIFAS score was 63.12 (±7.34). The Polish version of the IIFAS is a reliable and appropriate measure of women's attitudes towards infant feeding in Polish settings, with acceptable psychometric properties and construct validity.


Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.


Human recombinant monoamine oxidase B as reliable and efficient enzyme source for inhibitor screening.
Interest in inhibitors of monoamine oxidase type B (MAO B) has grown in recent years, due to their therapeutic potential in aging-related neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. This study is devoted to the use of human recombinant MAO B obtained from a Baculovirus expression system (Supersomes MAO B, BD Gentest, MA, USA) as reliable and efficient enzyme source for MAO B inhibitor screening. Comparison of inhibition potencies (pIC50 values) determined with human cloned and human platelet MAO B for the two series of MAO B inhibitors, coumarin and 5H-indeno[1,2-c]pyridazin-5-one derivatives, showed that the difference between pIC50 values obtained with the two enzyme sources was not significant (P>0.05, Student's t-test). Hence, recombinant enzyme is validated as convenient enzyme source for MAO B inhibitor screening.


Intracranial tumors with risk of dissemination in neuroaxis.
The experience of the Radiotherapy Service, Clínica Puerta de Hierro, Madrid (Spain), in the treatment of intracranial tumors with risk of neural axis dissemination is analyzed. In 15 years (1964-1979) 415 primary central nervous system tumors were studied and treated; 67 corresponded to tumors with risk of meningeal dissemination. Clinical dissemination in cerebrospinal fluid was proven in 14 patients. The actuarial survival of 10 years for patients with neural axis dissemination, without prophylactic treatment to the neuroaxis, is 14% with an average survival of 10.5 months. In approximately 20% of meduloblastomas, ependymal and pineal region tumors, meningeal metastases at some distance from the primary tumor can take place. Patients at risk wtih these types of neoplasia must be identified, and an adequate radical therapeutic focus devised, not only for the primary tumor, but also for the risk of dissemination.


P-loop catalytically assisting the enzymatic cleavage of single-stranded DNA.
We demonstrated that a P-loop, a looped complex formed inside duplex DNA by adding peptide nucleic acids (PNA), acts catalytically as a template for enzymatic cleavage of single-stranded probe oligodeoxynucleotides (ODN). A PD-loop complex formed from P-loop and probe ODN was digested efficiently by a restriction enzyme, and the truncated probe ODN was released. The P-loop nicked by the enzyme can form PD-loop again with another probe ODN, and then assisted the enzymatic cleavage of an excess of probe ODN. In addition, by using dumbbell-formed ODN as a probe ODN, the efficiency of the P-loop-assisted ODN cleavage was enhanced considerably as compared with that of linear ODN. Thus, the method utilizing P-loop will make it possible to amplify the sequence information of duplex DNA via a catalytic cleavage of probe ODNs.


[Dynamics of the blood circulatory indices in the crew of the Saliut space station in a functional test under physical load].
On the 4th, 9th, 16th and 21st days of the "Salyut" mission the crewmembers performed exercises with a load of about 1100 kgm. The results were compared with those obtained on the Earth. Immediately after the tests the crewmembers showed an increased heart rate and greater changes in the diastolic and pulse pressure, cardiac output and left ventricular ejection time. The above parameters returned to the normal at a slower rate. A comparison of the values recorded on different flight days did not demonstrate a distinct correlation between the changes and time of the weightlessness exposure.


Periodontal considerations in restorative dentistry. Part 2: Prosthodontic considerations.
This is the second of two articles to examine the periodontal considerations necessary in restorative dentistry. In it, the authors look closely at the considerations specific to fixed and removable prosthodontics.


3T3-L1 preadipocyte differentiation and poly(ADP-ribose) synthetase.
Differentiation of 3T3-L1 preadipocytes, induced by methyl-isobutylxanthine (MIX), dexamethasone (DEX), and insulin, results in cells with the morphological and biochemical characteristics of adipocytes. Following incubation of 3T3-L1 cells with MIX, DEX, and insulin, poly(ADP-ribose) synthetase activity decreased abruptly, remained low for several hours and then increased; this rise was delayed by readdition of MIX, DEX, and insulin. The transient reduction in poly(ADP-ribose) synthetase activity in 3T3-L1 cells occurred prior to the appearance of the adipocyte phenotype induced by the above agents. It was not observed when preparations were assayed in the presence of DNase I, indicating that poly(ADP-ribose) synthetase activity was masked following treatment with MIX, DEX, and insulin. The change in synthetase activity represents the earliest alteration of a specific enzyme yet detected during the differentiation of 3T3-L1 cells. It appears to be differentiation specific since nondifferentiating 3T3-C2 control cells did not exhibit changes in poly(ADP-ribose) synthetase activity when treated with MIX, DEX, and insulin. The transient reduction in activity may be an early event in differentiation which reflects changes in chromatin structure.


Indian major basmati paddy seed varieties images dataset.
The dataset contains images of 10 out of 32 notified Indian basmati seeds varieties (by the Government of India). Indian basmati paddy varieties included in the dataset are 1121, 1509, 1637, 1718, 1728, BAS-370, CSR 30, Type-3/Dehraduni Basmati, PB-1 and PB-6. Moreover, several images of other seeds and related entities available in the household have also been included in the dataset. Thus, the dataset contains 11 classes such that ten classes contain images from ten different basmati paddy varieties. In contrast, the 11th class- named "Unknown" contains images from a mixture of two morphologically similar paddy varieties (1121 and 1509), different pulses, other grains and related food entities. The Unknown class is useful in discriminating the paddy seeds from other types of seeds and related food entities. All the images were captured (in standard conditions) manually using an apparatus developed in-house and a tablet with a five-megapixel camera (5MP). The camera was used to capture 3210 RGB coloured images in JPG format. The data pre-processing was performed to generate the ready-to-use images for training and testing machine learning-based models. AI-based paddy seed variety classification models have been developed using the dataset. The dataset can be used to generate different types of AI-based models for adulteration detection, automated classification models (along with independent devices) at the time of rice threshing, and to increase the classification potential (Supplementing images representing additional basmati varieties).


Listing on MEDLINE: A new milestone for the Australian Journal of Physiotherapy.
The Editorial Board is pleased to announce that, commencing with the first issue of Volume 47, the Australian Journal of Physiotherapy will now be listed in the prestigious MEDLINE database. It has long been a goal of past and current Editorial Boards to achieve listing with MEDLINE because of the international exposure that such listing brings. Of the estimated 13,000 to 14,000 biomedical titles currently published throughout the world, about 4,500 titles are indexed and included in the MEDLINE database. MEDLINE is the principal online bibliographic citation database of MEDLARS system of the National Library of Medicine (USA) and includes all the citations published in Index Medicus as well as the citations published in two other indices, the Index to Dental Literature (IDL) and the International Nursing Index (INI).


TKSA-MC: A web server for rational mutation through the optimization of protein charge interactions.
The TKSAMC is a web server which calculates protein charge-charge interactions via the Tanford-Kirkwood Surface Accessibility model with the Monte Carlo method for sampling different protein protonation states. The optimization of charge-charge interactions via directed mutations has successfully enhanced the thermal stability of different proteins and could be a key to protein engineering improvement. The server presents the electrostatic free energy contribution of each polar-charged residue to the protein native state stability. Specific residues are suggested to be mutated for improving thermal stability. The choice of a residue is based on its fraction of side chain exposed to solvent and its positive free energy contribution, which tends to destabilize the protein native state. Any residue energy contribution can be shown as a function of pH condition. The web server is freely available at UNESP (São Paulo State University - DF/IBILCE): http://tksamc.df.ibilce.unesp.br and also on GitHub https://github.com/contessoto/tksamc.


Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.
An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin. We recruited patients with lamotrigine-induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958 British birth cohort was used as a control (n = 1296). HLA-A*3101 was imputed from genome-wide association study data. We applied genome-wide association to study lamotrigine- and phenytoin-induced cADR, and total cADR cases combined. Neither HLA-A*3101 nor any other genetic marker significantly predicted lamotrigine- or phenytoin-induced cADRs. HLA-A*3101 does not appear to be a predictor for lamotrigine- and phenytoin-induced cADRs in Europeans. Our genome-wide association study results do not support the existence of a clinically relevant common variant for the development of lamotrigine- or phenytoin-induced cADRs. As a predictive marker, HLA-A*3101 appears to be specific for carbamazepine-induced cADRs.


Does peer teaching improve academic results and competencies during medical school? A mixed methods study.
This study investigates the impact of Peer-Assisted Learning (PAL) in clinical skills on peer teachers' academic scores and competencies; however, controversy remains on this topic, and concrete evidence on its impact lacking. We performed a mixed methods study combining a retrospective cohort study with a modified Delphi survey. Peer teachers and Skills Lab faculty members participated in this study. A validated questionnaire, the CanMEDS Competency Based Inventory (CCBI), and group interviews were used to assess the outcomes of PAL. Our results were also triangulated with literature data. In 3 consecutive cohorts of medical students (n = 311), 78 participated in PAL. Peer teachers obtained higher scores from the start of the study, at different timepoints in medical school, and on their final scores compared to all other students. Interestingly their progress followed the same path and magnitude as other well-performing students. However, based on our findings from a modified Delphi survey (CCBI interviews) and a literature review, we found further supporting evidence for a positive impact of PAL on the competencies of physical skills (medical expert), teamwork and leadership (collaborator), lifelong learning (scholar), and for admitting uncertainty/limits (professional) within the CanMEDS roles. We conclude that higher achieving students are more likely to volunteer for a peer tutoring program; however this does not significantly augment their academic scores as compared to above well-performing non-teaching fellow students. Importantly, our modified Delphi survey indicated which CanMEDS roles were positively impacted by PAL: medical expert, collaborator, scholar and professional.


A comparative dosimetric analysis of virtual stereotactic body radiotherapy to high-dose-rate monotherapy for intermediate-risk prostate cancer.
Stereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDR's dosimetry can be achieved by virtual SBRT. Patients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5Gy×4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue- and PTV-prioritized plans were generated. From the normal tissue-prioritized plan, HDR and virtual SBRT achieved similar PTV V100 (93.8% vs. 93.1%, p=0.20) and V150 (40.3% vs. 42.9%, p=0.69) coverage. However, the PTV V200 was not attainable with SBRT (15.2% vs. 0.0%, p<0.001). The rectal Dmax was significantly lower with HDR (94.2% vs. 99.42%, p=0.05). The rectal D2 cc was also lower (60.8% vs. 71.1%, p=0.07). Difference in D1 cc urethral dose was not significantly different (87.7% vs. 75.2%, p=0.33). Comparing the PTV-prioritized plans, the rectal Dmax (94.2% vs. 111.1%, p=0.05) and mean dose (27.1% vs. 33.3%, p=0.03) were significantly higher using SBRT, and the rectal D2 cc was higher using SBRT (60.8% vs. 81.8%, p=0.07). HDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities.


Infantile Sandhoff's disease: multivoxel magnetic resonance spectrosecopy findings.
Sandhoff's disease is a rare, genetic lysosomal storage disease leading to delayed myelination or demyelination. Although neuroimaging findings in this disease have been reported previously, magnetic resonance spectroscopy findings have not been reported. In this report, we present magnetic resonance imaging and magnetic resonance spectrscopy features of two cases with Sandhoff's disease. Magnetic resonance spectroscopy revealed findings indicating widespread demyelination in both cases and neuroaxonal loss and anaerobic metabolism in the second case. Magnetic resonance spectroscopy could provide useful information in the explanation of the clinical picture of cases with Sandhoff's disease.


The effects of external diaphragmatic pacing on diaphragm function and weaning outcomes of critically ill patients with mechanical ventilation: a prospective randomized study.
Diaphragmatic pacing can improve diaphragm function, which is beneficial for the prognosis of patients treated with prolonged mechanical ventilation (MV). While most previous studies have focused on the role of implanted diaphragm pacing (IDP), our study is the first to examine the effects of external diaphragmatic pacing (EDP) in mechanically ventilated patients. Specifically, the effect of EDP on diaphragm function, the success rate of weaning, the duration of MV (DMV), and the intensive care unit (ICU) length of stay (ILOS) were assessed. From September 2019 to December 2020, a total of 51 mechanically ventilated patients in the ICU of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University were enrolled and randomly divided into an EDP group of 27 patients and a control group of 24 patients. The control group received routine treatment, and the EDP group received EDP treatment in addition to routine treatment. The diaphragm excursion (DE), diaphragm thickening fraction (DTF), DMV, ILOS, and average survival time were recorded to evaluate efficacy. Patients treated with EDP had increased DE [exp(B) =1.86, 95% CI: 1.39 to 2.50, P<0.001] and DTF [exp(B) =1.35, 95% CI: 1.05 to 1.76, P=0.022], shortened weaning time (P=0.026) and prolonged average survival time (P<0.001) compared to patients who did not receive EDP therapy. Especially in cases with difficult weaning, the improvement of DE and DTF in the EDP treatment group was more obvious than that in the control group (P=0.013 and P=0.032). Moreover, the DTF upon attempted spontaneous breathing trial (SBT) was negatively correlated with the fraction of inspired oxygen (FiO2) [r=-0.54; 95% confidence interval (CI): -0.77 to -0.19; P=0.004], the arterial partial pressure of oxygen (PaO2) (r=-0.58; 95% CI: -0.79 to -0.25; P=0.001), the PaO2/FiO2 ratio (r=-0.52; 95% CI: -0.75 to -0.16; P=0.006), and the serum lactate concentration (Lac) (r=-0.39; 95% CI: -0.68 to 0.003; P=0.046). EDP treatment can effectively reduce the DMV and prolong the average survival time of mechanically ventilated patients. Chinese Clinical Trial Registry ChiCTR1900024096.


Autologous transplantation of bone marrow/blood-derived cells for chronic ischemic heart disease: a systematic review and meta-analysis.
Studies focused on cell therapy for chronic ischemic heart disease (CIHD) have been published with conflicting results. In this meta-analysis, we aimed to assess the effectiveness and safety of autologous bone marrow/blood-derived cell transplantation in patients with CIHD. Randomized controlled trials (RCTs) were identified in PubMed, OVID, EMBASE, and Cochrane Library reviews and reference lists of relevant articles. Weighted mean difference was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) using a random-effects model. Nineteen trials with a total of 886 patients were included. Compared with controls, patients who received transplantation of bone marrow/blood-derived cells had significantly improved LVEF (3.54%; 95% confidence interval [CI], 1.92%-5.17%; P < 0.001) and LVESV (-8.96 mL; 95% CI, -13.64 to -4.28 mL; P < 0.001). No significant improvement in LVEDV (-0.75 mL; 95% CI, -9.80-8.30 mL; P = 0.22) was detected. Subgroup analysis revealed that significant improvement in LVEDV was observed in patients with lower baseline LVEF. Moreover, there were trends in favor of a benefit for LV function and remodelling when intramyocardial cells were injected during coronary bypass surgery and the bone marrow mononuclear cell number was ≤ 1 × 10(8). Furthermore, cell therapy was associated with a significant decrease in all-cause death (relative risk: 0.49; 95% CI, 0.29-0.84; P = 0.01). Current evidence showed that cell therapy moderately improved left ventricle function and significantly decreased all-cause death in patients with CIHD and supports further RCTs with larger sample size and longer follow-up.


Portal response related to shunt occlusion by balloon-occluded retrograde transvenous obliteration may determine the prognosis of cirrhosis.
To determine the prognostic effect of portal hemodynamic responses after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) in cirrhosis patients. This retrospective study consisted of 37 cirrhosis patients (aged 62.5 ± 9.7 years) with medium- or large-grade GV treated with B-RTO. Portal hemodynamic response was assessed by the changes in flow volume in the portal trunk (PFV, mL/min) before and after the treatment. Group I showed increased PFV and group II showed no increase in PFV. The median observation period was 49.8 months (range, 4.7-150.3 months). All patients showed complete embolization of GV without any recurrence. There were 30 patients in group I and 7 patients in group II (decreased PFV in 6 and unchanged PFV in 1). The PFV at baseline was significantly lower in the former (583.5 ± 232.0 mL/min) than in the latter (880.7 ± 345.9 mL/min; P = 0.009). The survival rate was significantly lower in group II (83.3% at 1 year and 66.7% at 3 years) than in group I (96.7% at 1 year, 81.5% at 3 years, and 61.8% at 5 years; P = 0.012). The incidence of deterioration of the esophageal varices was 18/30 (60%) in group I and 5/7 (71.4%; P = 0.687) in group II. Multivariate analysis identified only no increase in portal response (hazard ratio, 8.086; P = 0.005) as an independent factor for poor prognosis. Balloon-occluded retrograde transvenous obliteration for GV may result in a poor prognosis when portal hemodynamics shows no increase in portal response.


Sheets obtained by radiation polymerization for enzyme immunoassay.
Immobilized anti-alpha-fetoprotein sheets, which were attached to sticks, for enzyme immunoassay of alpha-fetoprotein were prepared by radiation polymerization of hydrophilic monomers. The relationship between the preparation conditions and the activity of the sheets was studied. The activity varied with monomer concentration, hydrophilicity of polymer matrix, the amount of coating solution, and antibody concentration. The sheets obtained at relatively low monomer and antibody concentrations appeared to give a high activity. It was found that the sheets are applicable for the enzyme immunoassay of alpha-fetoprotein with high sensitivity.


The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study.
Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686-6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487-6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.


CFTR targeting in epithelial cells.
We used polarized and nonpolarized colonic cell lines (HT-29) to correlate CFTR function and expression with epithelial cell morphogenesis. Unpolarized cells express levels of CFTR mRNA and protein that are equivalent to those observed in polarized cells, and the extent of CFTR glycosylation is also similar. Despite these similarities in CFTR expression, the polarized cells secreted Cl in response to cAMP, but there was no cAMP-stimulated Cl conductance response in the unpolarized cells. In the polarized cells, CFTR is localized in the apical membrane domain, but in unpolarized cells the protein is retained at a perinuclear location. These findings indicate that a peripheral targeting mechanism, distal to the Golgi cisternae, controls the progression of N-linked glycoproteins like CFTR to the apical membrane. This targeting process does not become active until epithelial cells polarize. It may determine whether mutant forms of CFTR are targeted to the apical membrane.


Can You Believe Your Patients If They Say They Have Quit Smoking?
To determine the reliability of self-reported smoking status in the orthopaedic trauma population and determine if certain patient factors might predispose inaccurate self-reported smoking cessation. Prospective. Level I trauma center. Two hundred forty-seven orthopaedic trauma patients were included in the study. In-office measurement of exhaled carbon monoxide (CO). Self-reported smoking cessation with exhaled CO measurements. A total of 906 self-reported surveys were completed over 4 follow-up visits. Of the responses indicating smoking cessation (n = 174), 12.6% [95% confidence interval (CI), 0.081-0.185] reported smoking cessation with positive CO readings, suggesting inaccurate self-reporting of smoking status. Over 20% of those patients inaccurately reporting abstinence did so more than once. The odds of inaccurate self-reporting was 3 times higher in patients with no insurance or government insurance [odds ratio (OR), 3.5; 95% CI, 1.1-11.0; P = 0.043] and in the unemployed (OR, 3.3; 95% CI, 0.97-8.57; P = 0.049). Self-reported smoking status in the orthopaedic population is fairly reliable, with 13% of patient's inaccurately self-reporting smoking cessation despite knowing their smoking status was being measured. Clinicians should be aware of the potential for inaccuracy in self-reported smoking cessation, particularly in patients with the identified socioeconomic factors. Point-of-care testing before elective trauma procedures to confirm smoking status might have a role if the procedure outcome is highly dependent on smoking status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


[Temperament and alcoholic behavior in medical students].
The Tunisian medical student population is very heterogeneous. This heterogeneity is based among other things on temperamental differences between different students and their behavior and strategies to cope with the requirements and constraints of medical studies. We conducted this study aiming: to determine the prevalence of alcohol use in a student population at Sfax Medical School and to evaluate the factors associated with this use; to study the relationship between affective temperament and alcohol consumption among medical students. We conducted a descriptive and analytical cross-sectional study in the form of a survey between July 2018 and January 2019 among students (aged between 19 and 30) recruited from the University of Medicine of Sfax during their internship in the psychiatric department "A" at CHU HédiChaker of Sfax. We used a pre-established survey sheet based on data from the substance use and affective temperament literature in medical students that was completed by the participants after obtaining their consent and having explained the anonymity and confidentiality of the questionnaire. This sheet included a section on student sociodemographic characteristics, a second part describing the history and characteristics of alcohol consumption and the evaluation of alcohol consumption through the Alcohol Use Disorders Identification Test (AUDIT), and a third part for temperament evaluation by TIME-A, and Temperament Evaluation of Memphis Pisa Paris and San Diego Auto-questionnaire. We recruited 136 students with an average age of 21.63 years (SD 2 years) and a sex ratio (H/F) of 0.66. Alcohol consumption was observed among 19.8 % of students surveyed, 19.1 % of whom were occasional consumers. The mean age of onset of alcohol consumption was 18.48 years (SD 1.76 years). All consumer students had started using alcohol with their friends. The desired effect was euphoric in 74 % of cases, sleeping for 14.8 % of them. Among consumers, the average score at AUDIT was 6.44 (SD 5.3). Among them 70.4 % had a risk-free consumption (score of 8 or less); 14.8% were at risk (score 9-12) and 11.1 % were likely alcohol dependent (score>12). The evaluation of affective temperament according to TIME-A showed that the cyclothymic and hyperthymic temperament scores were the highest among the students (respectively 5.5 and 4). The analytical study showed that alcohol dependence was significantly more common among male students (p=0.048). Alcohol use was significantly more common among students who smoke (p<0.001) and those who consume cannabis (p<0.001). The bivariate correlation showed that more students had a high score of depressive temperaments (r=0.18, p=0.032), irritable (r=0.2, P=0.018) and hyperthymic (r=0.27, p=0.001). The higher their scores on the AUDIT scale, the more alcohol-dependent they were. The implementation of preventive measures is an obvious emergency. In the same way, taking into account the difference in affective temperaments in this very particular population could have a grandiose importance and an interesting impact both in the screening and in the care of these students.


Risk factors associated with suicide attempt in young French people.
Demographic data, personal and familial characteristics, as well as DSM-III-R-based psychiatric diagnoses were collected in 369 adolescents and young adults aged between 15 and 29 years, referred to an Emergency Department for psychological problems. In total, 60% of them were suicide attempters. Separations before the age of 12 years and depression in the family emerged as the main features distinguishing the suicidal group from the psychiatric control group. Fifty per cent of suicide attempters were repeaters. Fostering during childhood, suicide attempts and depression in the family were found to be risk factors for repeated self-attempts. These results support the view that significant levels of dysfunction, together with increased psychiatric morbidity, especially suicidal behaviour, characterize the families of young self-attempters.


Rifampicin prevents virosome localization of L65, an essential vaccinia virus polypeptide.
In contrast to its irreversible effect on the Escherichia coliRNA polymerase beta-subunit, the antibiotic rifampicin reversibly inhibits vaccinia virus morphogenesis at a step during the formation of immature viral particles. The protein affected by the presence of rifampicin is L65, a major late vaccinia polypeptide to which mutations that confer rifampicin resistance have been mapped. We now provide evidence using a monospecific anti-L65 serum in concert with immunofluorescence and sucrose gradient analysis that the mechanism of action of rifampicin on vaccinia virus replication involves the inhibition of localization of L65 to the viral factories (virosomes) thereby blocking further development. Studies on the expression and distribution of L65 during the infection cycle reveal that L65 is a stable, nonglycosylated late protein associated with virions. These results are discussed in relationship to the possible in vivo functions of the L65 protein.


Time to recovery and determinants of severe acute malnutrition among 6-59 months children treated at outpatient therapeutic programme in North Gondar zone, Northwest Ethiopia: a prospective follow up study.
Despite the available interventions to tackle nutritional problems, there is scarce information on time to recovery and its determinants among children with SAM in Ethiopia. This study was aimed at finding the time to recovery and determinants among 6-59 months children with severe acute malnutrition treated at an outpatient therapeutic programme in North Gondar zone, northwest Ethiopia. Facility based prospective follow up study was conducted from March 24 to May 24, 2017. A total of 408 children with the age of 6-59 months were included in the study. Structured interviewer administered questionnaire was used. Anthropometric measurements were conducted every week. The median time of recovery, Kaplan Meier (KM) curve, and log rank test were computed. Both bi-variable and multivariable Cox regression model was fitted. To establish an association between time to recovery and its determinants 95% confidence interval (CI) and p-value < 0.05 were used. Proportional hazard assumption was checked graphically and using Schoenfeld residual test. Out of 389 children, 254 (65.3%) recovered. The median time to recovery was 38.5 ± IQR of 14 days. Children with diarrhoea AHR = 0.81 with 95% CI (0.73, 0.99), children taken amoxicillin AHR = 2.304 with 95% CI (1.68-3.161), and had vomiting at admission AHR = 0.430 with 95% CI (0.205, 0.904) were significant predictors of time to recovery. The overall time to recovery has not met the minimum sphere international standard which was lower than 75%. It is advisable to give emphasis to patients with diarrhoea and vomiting.


Antenatal diagnosis of renal anomalies with ultrasound. III. Bilateral renal agenesis.
Bilateral renal agenesis is a lethal congenital anomaly. A reliable prenatal diagnosis is extremely important, since it may offer options for pregnancy termination or may change obstetric management in the third trimester. This study examined the accuracy of ultrasound in making an antenatal diagnosis of bilateral renal agenesis in three different populations: (1) patients with a family history of bilateral renal agenesis, (2) patients diagnosed during the course of a routine scan, and (3) patients referred because of a previous suspicious ultrasound examination in a level I ultrasound facility. In group A there were three true positive, 13 true negative, no false negative, and no false positive diagnoses. In group B there were three true positive and no false positive diagnoses. In group C there were 12 true positive, 17 true negative, one false negative, and no false positive diagnoses. The value and potential pitfall of the different diagnostic criteria are discussed. We conclude that ultrasound is a valuable tool in the detection of intrauterine renal failure, although there are limitations to a specific diagnosis of bilateral renal agenesis.


Spatial separation of Golgi and ER during mitosis protects SREBP from unregulated activation.
Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that reside as inactive precursors in the endoplasmic reticulum (ER) membrane. After sterol depletion, the proteins are transported to the Golgi apparatus, where they are cleaved by site-1 protease (S1P). Cleavage releases the active transcription factors, which then enter the nucleus to induce genes that regulate cellular levels of cholesterol and phospholipids. This regulation depends on the spatial separation of the Golgi and the ER, as mixing of the compartments induces unregulated activation of SREBPs. Here, we show that S1P is localized to the Golgi, but cycles continuously through the ER and becomes trapped when ER exit is inhibited. During mitosis, S1P is associated with mitotic Golgi clusters, which remain distinct from the ER. In mitotic cells, S1P is active, but SREBP is not cleaved as S1P and SREBP reside in different compartments. Together, these results indicate that the spatial separation of the Golgi and the ER is maintained during mitosis, which is essential to protect the S1P substrate SREBP from unregulated activation during mitosis.


[COPD: bronchial and systemic inflammation].
Chronic obstructive pulmonary disease (COPD) is considered to be an inflammatory disease of the airways, in which there can be low-grade systemic inflammation. The etiology of this disease is multifactorial but is mainly due to an anomalous and amplified inflammatory response to tobacco smoke. This inflammatory response involves innate and acquired immunity. The latter is characterized by a Th1-type (CD8) response and its presence seems to be associated with progression to advanced stages of the disease. Currently, it is unknown whether bronchial and systemic inflammation are related or whether they act as independent compartments. Most of the available data on COPD are drawn from cross-sectional studies and consequently a causal relation between the possible inflammatory mediators and the genetic factors involved in pulmonary and extrapulmonary involvement in this disease cannot be established. Further studies are required that would allow the inflammatory response to be correlated with the distinct COPD phenotypes.


Time-resolved fluorescence studies on protoporphyrin IX-apohorseradish peroxidase.
The hemin moiety of horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 22.214.171.124) was removed and the apoprotein reconstituted with the fluorescent protoporphyrin IX. Steady-state and time-resolved fluorescence properties of the HRP(desFe) adduct were examined; the multifrequency phase and modulation method was utilized for lifetime and dynamic polarization studies. The emission spectrum of HRP(desFe) had maxima at 633 and 696 nm. The lifetime of this emission was characterized by a single exponential decay of 16.87 ns at 22 degrees C. Debye rotational relaxation times for HRP(desFe) were determined using both static (Perrin plot) and dynamic (differential phase and modulation fluorometry) methods; these two approaches gave values of 96 and 86 ns, respectively. A spherical protein of HRP's molecular weight and partial specific volume would be expected to have a Debye rotational relaxation time, at 22 degrees C, in the range of 50 to 60 ns, depending upon the extent of hydration. Hence our results indicate that HRP(desFe) is asymmetric; the global rotational relaxation times observed are consistent with those of a prolate ellipsoid with an axial ratio of 3:1.


Bimetallic nanoparticles decorated hollow nanoporous carbon framework as nanozyme biosensor for highly sensitive electrochemical sensing of uric acid.
An ultrasensitive electrochemical biosensor was developed to identify the low levels of uric acid (UA) in human serum. The gold/cobalt (Au/Co) bimetallic nanoparticles (NPs) decorated hollow nanoporous carbon framework (Au/Co@HNCF) was synthesized as a nanozyme by pyrolysis of the Au (III)-etching zeolitic imidazolate framework-67 (ZIF-67). The external Au NPs combined with internal Co NPs on the hollow carbon framework exhibited enhanced activity for UA oxidation, thereby generating superior signals. Accordingly, the Au/Co@HNCF biosensor presented ranking performances with a low detection limit of 0.023 μM (S/N = 3), an ultrahigh sensitivity of 48.4 μA μM-1 cm-2, and an extensive response in the linear region of 0.1-25 μM and the logarithmic region of 25-2500 μM. Owing to the ordered nanoporous framework and carbon interfacial features, the Au/Co@HNCF biosensor displayed adequate selectivity for UA sensing over a series of biomolecules. In addition, the Au/Co@HNCF biosensor was employed to quantify UA in human serum samples. The test results were basically consistent with those of a commercial apparatus, and thus demonstrated that the proposed Au/Co@HNCF biosensor was reliable for UA determination in clinical research.


Short- and long-term effect of high versus low-to-moderate intensity exercise to optimise health-related quality of life after oncological treatment-results from the Phys-Can project.
This study aimed to evaluate the effect of high intensity (HI) vs low-to-moderate intensity (LMI) exercise on health-related quality of life (HRQoL) up to 18 months after commencement of oncological treatment in patients with breast, colorectal or prostate cancer. In addition, we conducted a comparison with usual care (UC). Patients scheduled for (neo)adjuvant oncological treatment (n = 577) were randomly assigned to 6 months of combined resistance and endurance training of HI or LMI. A longitudinal descriptive study (UC) included participants (n = 89) immediately before the RCT started. HRQoL was assessed by EORTC QLQ-C30 at baseline, 3, 6 and 18 months (1 year after completed exercise intervention) follow-up. Linear mixed models were used to study the groups over time. Directly after the intervention, HI scored significant (P = 0.02), but not clinically relevant, higher pain compared with LMI. No other significant difference in HRQoL was found between the exercise intensities over time. Clinically meaningful improvements in HRQoL over time were detected within both exercise intensities. We found favourable significant differences in HRQoL in both exercise intensities compared with UC over time. This study adds to the strong evidence of positive effect of exercise and shows that exercise, regardless of intensity, can have beneficial effects on HRQoL during oncological treatment and also for a substantial time after completion of an exercise intervention. In this study, for one year after. Patients can be advised to exercise at either intensity level according to their personal preferences, and still benefit from both short-term and long-term improvements in HRQoL.


[Polymorphisms of four STRs and their associations with IDDM in Chinese Han population].
To obtain the polymorphic data of short tandem repeat(STR) loci of D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the association of these four STR loci with insulin-dependent diabetes mellitus(IDDM). The polymorphisms of the four STRs were studied by polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients with IDDM. Seven alleles at D15S657 locus, 5 alleles at D11S1369 locus, 7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and allele A(4) at D6S2420 locus were increased significantly in patients with IDDM, compared to those in the control group. The four STRs, used as genetic markers, were suitable for case-control study, forensic medicine identification and population genetic study. There is an association between the polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.


Synthesis and conformational analysis of a simplified inositol-model of the Streptococcus pneumoniae 19F capsular polysaccharide repeating unit.
Carbohydrate mimics have been studied for a long time as useful sugar substitutes, both in the investigation of biological events and in the treatment of sugar-related diseases. Here we report further evaluation of the capabilities of inositols as carbohydrate substitutes. The conformational features of an inositol-model of a simplified repeating unit corresponding to the capsular polysaccharide of Streptococcus pneumoniae 19F has been evaluated by computational analysis, and compared to the native repeating unit. The inositol mimic was synthesized, and its experimental spectroscopic data allowed for verification of the theoretical results.


Mid-term clinical outcomes and complications of primary total knee arthroplasty in hemodialysis patients: a retrospective comparative cohort study.
Numerous patients who receive hemodialysis (HD) undergo total knee arthroplasty (TKA) due to advanced knee joint arthritis. However, there are few studies that describe the clinical outcomes and complications of TKA in HD patients. This study investigated the mid-term results of TKA in patients undergoing HD. This single-center retrospective study compared clinical and surgical outcomes following TKA in patients who were receiving HD with those who were not. We used propensity scores to match 21 knees of 18 patients who received HD to 706 knees of 569 patients who had not received HD, from a total of 727 knees (587 patients) that underwent primary unilateral TKA. The clinical outcomes were evaluated using the American Knee Society Score-knee (AKSS-knee) and AKSS-function scores. The primary surgical outcome measure was the number of knees with postoperative complications. In both the HD and non-HD groups, postoperative AKSS-knee and function scores significantly improved when compared to preoperative values. Postoperative AKSS-knee and function scores were not significantly different between the groups. The number of knees with postoperative complications was larger in the HD group than the non-HD group within the first postoperative month, 0-12 months, 12-24 months, 0-24 months, and two years after surgery. Additionally, in the HD group, more complications occurred in the first month than any subsequent month in the two years after surgery. TKA improves AKSS-knee and function scores equivalently for HD patients and non-HD patients. However, HD patients develop more complications after TKA, especially within the first month. Therefore, surgeons who perform TKA for HD patients should obtain informed consent after explaining the possible complications, and HD patients should be carefully observed following TKA.


Carry-over of deoxynivalenol into eggs of laying hens - Preliminary results.
Carry-over of deoxynivalenol (DON) into eggs was investigated within the scope of a 16-week experiment with laying hens, in which the birds were fed a maize-based diet containing DON at 11.9 mg/kg dry matter. Eggs were collected during weeks 2, 4, 8, and 16. DON and its metabolite deepoxy-DON were analysed separately in freeze-dried yolk and albumen. Yolk was extracted with water and the extract was purified using an immunoaffinity column (IAC). Albumen was extracted with acetonitrile-water and the extract was pre-cleaned before applying an IAC. All albumen and some yolk samples were incubated with β-glucuronidase prior to extraction. DON and de-epoxy-DON were determined by high performance liquid chromatography (HPLC) with diode array detection (DAD). The detection limits of both toxins were 20 ng/g and 15 ng/g in freezedried yolk and albumen, respectively, corresponding to approximately 10 ng/g and 2 ng/g in fresh samples. The recovery of DON/de-epoxy-DON in spiked samples (50-200 ng/g) was 87/83% (yolk) and 87/77% (albumen) with coefficients of variation of 4-15%. Neither DON nor de-epoxy-DON were detected in any of the samples. In order to achieve lower detection limits, the methods are currently optimized. However, these preliminary results indicate that eggs do not contribute significantly to the dietary DON intake of the consumer.


Twin-to-twin transfusion syndrome at 11 weeks of gestation.
Second-trimester twin-to-twin transfusion is well known, but first-trimester cases rarely have been described. We present the case of a monochorionic twin at 11+0 weeks of gestation with single increased nuchal translucency and normal karyotypes. At 12+5 weeks of gestation, double intrauterine death was diagnosed, followed by delivery of a strikingly red and white fetus.


Temperature-dependent 3-D CuI coordination polymers of calix[4]-bis-dithiacrown: crystal-to-crystal transformation and photoluminescence change on coordinated solvent removal.
The temperature-dependent assembly of two 3-D CuI coordination polymers containing calix[4]-bis-thiacrown with different networking motifs are reported. Upon removal of the coordinated solvent molecules the initial solvent-coordinated polymer undergoes a unique single-crystal-to-single-crystal transformation to the desolvated polymer. Structural characteristics observed in the solvent-coordinated and the desolvated polymers also reveal related solvato-photolunimescence "off-on" behavior.


Responsiveness of IGF-I and IGFBP-3 to therapeutic intervention in children and adolescents with Crohn's disease.
Abnormal linear growth is common in childhood and adolescent Crohn's disease. We have studied the concentrations of the inflammatory marker CRP and of serum IGF-I and IGFBP-3 in patients with active Crohn's disease and have assessed the changes in these parameters during therapeutic intervention with enteral nutrition or intestinal resection. Children and adolescents attending the inflammatory bowel disease clinic at our hospital underwent treatment either with enteral nutrition (Study A) or intestinal resection (Study B). These are two separate studies and the results cannot be compared. Serum concentrations of CRP, IGF-I and IGFBP-3 were determined at 0, 2, 8 and 16 weeks after start of enteral nutrition and in addition to height velocity, at 0 and 6 months after intestinal resection. Study A: 14 patients, 9 male, 5 female, median age 12.5 years (range 7.0-17.2), puberty stage 1 (n = 13), stage 3 (n = 1). All had active Crohn's disease. Study B: 9 patients, 7 male, 2 female, median age 13.5 years (range 7.8-16.5), puberty stage 1 (n = 5), stages 2-4 (n = 4). All had Crohn's disease resistant to medical therapy. Crohn's disease was confirmed radiologically, endoscopically and histologically. Disease activity was scored using the Lloyd Still index (LSI). Study A: nutritional support was with a polymeric, casein-based formula feed AL 110. Study B: surgical procedures were small bowel resection (n = 2), right hemicolectomy (n = 5), subtotal colectomy (n = 2). Study A: weight SDS, CRP, IGF-1 and IGFBP-3 were measured at 0, 2, 8, 16 weeks after start of enteral feeding. Study B: height velocity, CRP, IGF-I and IGFBP-3 were measured 0, 6 months after intestinal resection. Medians and ranges were used. Significance of changes was calculated using the Wilcoxon rank test for the analysis of paired data. Study A: median LSI before treatment was 39 and increased after 8 weeks of enteral nutrition to 60 (P < 0.05). Weight SDS increased at 8 and 16 weeks (P < 0.05) compared to pretreatment. CRP was elevated at 0 weeks, falling during treatment. Median (range) values (normal < 5 mg/l) at 0 at 2, 8, 16 weeks were 53 mg/l (15-150), 8 mg/l (5-25), 7 mg/l (5-83) and 14 mg/l (5-39), all P < 0.001 compared with pretreatment. Median IGF-I-values increased during treatment. Median (range) values at 0, 2, 8, 16 weeks (all P < 0.005) compared to pretreatment, median (range) values at 0, 2, 8, 16 weeks were 78 micrograms/l (50-204), 131 micrograms/l (73-251), 119 micrograms/l (77-291) and 133 micrograms/l (67-497), all P < 0.005 compared to pre-treatment. IGFBP-3 levels increased during treatment. Median (range) values at 0, 2, 8, 16 weeks were 2.4 mg/l (1.4-3.1), 2.9 mg/l (1.8-4.6), 3.0 mg/l, 3.2 mg/l (1.8-4.5), all P < 0.01 compared to pretreatment. Study B: height velocity increased during 6 months after surgery. Median (range) values; 3.3 cm/year (0-8.3) before surgery, 8.4 cm/year (2-12.6) 6 months post-surgery, P < 0.01. Median (range) CRP values fell from 45 mg/l (5-150) to 8 mg/l (5-31) and IGF-I-values increased from 163 micrograms/l (64-286) to 226 micrograms/l (71-391). These changes were not statistically significant. IGFBP-3 values did not change. The IGF system, as shown by serum IGF-I and IGFBP-3, is responsive to therapeutic intervention in active Crohn's disease. It is likely that a combination of decreased inflammatory activity and improved nutrition contributes to these changes.


Denitrification of wastewater containing high nitrate and calcium concentrations.
The removal of nitrate from rinse wastewater generated in the stainless steel manufacturing process by denitrification in a sequential batch reactor (SBR) was studied. Two different inocula from wastewater treatment plants were tested. The use of an inoculum previously acclimated to high nitrate concentrations led to complete denitrification in 6h (denitrification rate: 22.8mg NO3- -N/gVSSh), using methanol as carbon source for a COD/N ratio of 4 and for a content of calcium in the wastewater of 150mg/L. Higher calcium concentrations led to a decrease in the biomass growth rate and in the denitrification rate. The optimum COD/N ratio was found to be 3.4, achieving 98% nitrate removal in 7h at a maximum rate of 30.4mg NO3- -N/gVSSh and very low residual COD in the effluent.


Altered metabolism of phospholipids in the lung of rats with peritonitis.
Pulmonary alterations after shock and sepsis, described clinically as shock lung or adult respiratory distress syndrome, are of great importance in intensive care. Pathogenetically an alteration of the surfactant system of the lung is often discussed. Since phospholipids are constituents of lung surfactants, phospholipid metabolism is investigated in experimental peritonitis in rats in our laboratory. 15 hours after inducing a peritonitis, the lung incorporates more oleic acid than that in animals of the reference group. 33 hours after inducing peritonitis, the capacity of the lung to incorporate choline and fatty acids is markedly reduced, histologically the lungs represent morphological equivalents of the so-called shock lung at this time. Therefore we conclude, that an alteration of phospholipid metabolism with a diminished and/or altered synthesis of lung surfactant plays, at least in part, an important role in the pathogenesis of respiratory distress in sepsis and peritonitis.


Orbital fracture evaluation by coronal computed tomography.
Coronal computed tomography produces orbital scans in a plane that is analogous to Caldwell-view x-ray films. Coronal computed tomography permits simultaneous visualization of the orbital walls and the orbital soft tissues, including all extraocular muscles. Using coronal computed tomography, we studied a series of patients with radiographically proven orbital floor fractures. We studied in detail three of these patients, one with a linear orbital floor fracture, one with a depressed orbital floor fracture, and one with a severely comminuted orbital floor. In two patients, coronal computed tomography showed inferior rectus muscle entrapment, which was confirmed at the time of surgery. In each patient, some bone fragments could be seen more discreetly on coronal computed tomography than on conventional polytomes. Coronal computed tomography may be used to help confirm extraocular muscle entrapment in patients with orbital floor fractures. Coronal computed tomography can also be used to examine patients with possible intraorbital foreign bodies, unexplained reduction of vision, or severely displaced bone fragments.


Respiratory medical societies and the threat of bioterrorism.
Respiratory medical societies throughout the world have an important role in helping governments to develop public policy to counter the threat of bioterrorism.


Sodium nitroprusside ameliorates lead toxicity in rice (Oryza sativa L.) by modulating the antioxidant scavenging system, nitrogen metabolism, lead sequestration mechanism, and proline metabolism.
As a toxic anthropogenic pollutant, lead (Pb) can be harmful to both plants and animals. Here, the effects of the application of nitric oxide (NO) donor, sodium nitroprusside (SNP, 0, 50, and 100 μM), on the morphological, biochemical, and molecular responses of rice plants under Pb (0, 150, and 300 μM) toxicity in hydroponic conditions were investigated. Pb stress decreased biomass, photosynthetic pigments, Fv/Fm value, and nitrogen (N) and increased the accumulation of hydrogen peroxide (H2O2), methylglyoxal (MG), malondialdehyde (MDA), and electrolyte leakage (EL) in rice seedlings. However, by improving the metabolism of chlorophyll and proline, SNP increased the content of chlorophyll and proline, restored the performance of the photosynthetic apparatus, and stimulated the growth of Pb-stressed rice seedlings. SNP by reducing the expression of HMA2 and increasing the expression of HMA3 and HMA4 caused the immobilization of Pb in the roots and reduced its transfer to the leaves. Adding SNP increased the activity of antioxidant enzymes and glyoxalase cycle and decreased H2O2, MG, MDA, and EL in the leaves of Pb-stressed rice seedlings. By upregulating the expression of genes GSH1, PCS, and ABCC1, SNP increased the accumulation of GSH and PCs in the roots and leaves and increased the plant's tolerance to Pb stress. By modulating the activity of enzymes involved in N metabolism, SNP increased the concentration of N and nitrate and decreased the concentration of ammonium in the leaves of Pb-stressed seedlings. Our study provides evidence that NO may become a promising tool for increasing the tolerance of rice plants to Pb toxicity.


[What type of curriculum in phthisiology should there be for medical students?].
Reconstruction in public health requires further improvement of medical personnel training by using more perfect curricula and methods of teaching. Different curricula on phthisiology are discussed in regard to disease pathomorphism and organization of personnel activity. It is advisable that the main attention should be paid to mastering differential diagnosis by medical students during their individual work.


The effect of calcium antagonists on the proteolytic degradation of low-density lipoprotein in HeLa cells.
The degradation of 125I-labelled low-density lipoproteins (LDL) in HeLa cells was significantly inhibited when the cells were incubated either with the calcium channel blocking agents D600 and verapamil, or with the lysosomotropic agent chloroquine. However, nifedipine, another blocker of Ca2+ channels, did not affect the degradation of 125I-labelled LDL. The association of 125I-labelled LDL with HeLa cells was increased in proportion to the concentration of D600, and 125I-labelled LDL was accumulated in lysosomal fractions as assessed by Percoll density gradient analysis. Some 80% of 125I-labelled LDL in lysosomes of HeLa cells treated with D600 was acid-insoluble. The rate of incorporation of [3H]acetate into digitonin-precipitable material was increased 4-fold in the cells treated with 40 micrograms/ml D600 compared with untreated cells, but that of [3H]mevalonate was not enhanced. About 8 h of preincubation of the cells with D600 or verapamil was required to inhibit the LDL degradation by 50% of the control activity. It was also found that the inhibitory action of D600 could be reversed by removal of D600 from the medium. The activities of lysosomal enzymes, cathepsin B, beta-hexosaminidase, and acid phosphatase, were significantly decreased when the cells were treated with D600 and chloroquine, but not with nifedipine. Blockers of Ca2+ channels which effect the activity of lysosomal enzymes, should be useful for the study of the lysosomal function.


Novel concept for posterior crossbite correction : Preliminary results.
The efficiency of dentoalveolar compensation involving both jaws for posterior crossbite correction using computer-aided design/computer-aided manufacturing (CAD/CAM) expansion and compression archwires was evaluated. Treatment outcome was tested against the null hypothesis that the transverse correction achieved would be significantly smaller than planned. This retrospective study included 64 patients (mean age 23.5 years, median 17.0, minimum/maximum: 9.0/63.0, standard deviation 13.7) with uni- or bilateral posterior crossbite. In all consecutively debonded patients, expansion and/or compression archwires were used for dentoalveolar correction involving both jaws. Plaster casts prior to (T1) and following treatment (T2) with completely customized lingual appliances (CCLA) were compared with the treatment plan represented by an individual target set-up. The statistical analysis was carried out using the Schuirmann TOST (two one-sided t‑tests) equivalence test on the basis of a one-sample t‑test with α = 0.025 to one side. The non-inferiority margin was set at δ = 0.5 mm. All posterior crossbites could be corrected by dentoalveolar compensation involving both jaws. The mean total correction achieved was 6.9 mm (mean maxillary expansion: 4.3 mm/mean mandibular compression: 2.6 mm) with a maximum of 12.8 mm. The transverse corrections achieved in both arches at T2 were equivalent to the planned corrections in the set-up (p < 0.001). The results of this study indicate that CAD/CAM expansion and compression archwires can be an efficient tool to achieve the desired correction in patients with a posterior crossbite even in more severe cases.


Myeloperoxidase as serum marker for detection of CMV infections and rejections in patients after liver or heart transplantation.
Rejection episodes and infections are common problems after organ transplantations (TX). Rejection can be diagnosed in liver-transplant (LTX) patients when liver-specific enzymes in the serum are elevated. As endomyocardial biopsy (EMB) is the gold standard for detecting heart transplant (HTX) rejection, serum parameters would permit more selective use of this invasive procedure. Cytomegalovirus (CMV) infections can have serious consequences for TX patients and so should be diagnosed and treated timely. At present, there are no suitable diagnostic methods other than CMV antigen pp65 and CMV polymerase chain reaction (PCR). Our study aimed to test the sensitivity of myeloperoxidase (MPO), an enzyme of neutrophilic granulocytes, as a new serum parameter in addition to established serum parameters and EMB for diagnosis of infection and rejection episodes after LTX and HTX. MPO in plasma from 246 blood samples (103 used for statistical analysis) from 27 patients (18 LTX and 9 HTX) was determined using ELISA; C-reactive protein (CRP), gamma-glutamyl-transpeptidase (GGT), white blood count and CMV pp65 antigen were monitored routinely. EMBs were performed at defined intervals after HTX. Results were analyzed with descriptive statistics, T-test, Wilcoxon test and Cox regression analysis, whereby a p<0.05 was viewed as significant. MPO values in TX patients with an infection (7 LTX, 2 HTX) were significantly higher than in TX patients without complications (control group) (253.9 microg/l vs. 116.6 microg/l, p=0.0194). In TX patients with rejections (6 LTX, 6 HTX), there is also a significant increase in comparison to controls (429.7 microg/l vs. 116.6 microg/l, p=0.0001). Data from individual TX patients, however, indicate that MPO levels rise distinctly earlier with infection (CMV) than with rejection, enabling earlier detection of the complication and initiation of suitable treatment. Our findings suggest that a larger and prospective study should be designed to evaluate the usefulness of MPO levels in assessing organ transplant recipients.


A comparison of metals in sediments and water in the River Nahr-Ibrahim, Lebanon: 1996 and 1999.
Rivers whose basins are underlain by carbonate rocks exhibit high pH, lower desorption of metals and possess high buffering capacity against acidic inputs to the river. The catchment of River Nahr-Ibrahim, Lebanon, is largely underlain by limestone. Compared to neighbouring countries, Lebanon is relatively fortunate since precipitation is high. However, recently a warming in temperature and a drop in precipitation has occurred, thus causing low water levels in rivers. The objective of this study is to investigate the variation of the total metal content (Fe, Mn, Zn, Cu, Pb and Cd) in bed sediments and water of River Nahr-Ibrahim between 1996 and 1999 (two years); and relate these variations to the effect of changes in human activities and/or due to the variations of precipitation rate, temperature and pH of water. Bed load sediments and stream water were collected simultaneously from five sampling sites. Water pH and temperature were determined in situ. Sediment samples were dried at room temperature and sieved; the sediment size < 75 microns size was retained. Water was analysed for major constituents and trace metals. Metals were extracted from sediments with aqua regia. Metal concentration in water and sediments were determined using ICP-MS technique. Data revealed a drop in metal concentrations (Zn, Cu, Pb, Cd) in sediments at quarry site after its closure. The decrease in precipitation rate, lowering the level of water and the dilution of industrial discharges and decrease in water pH led most probably to the desorption of metals from sediments into the water.


The Wedding Bells Sound Really Good! iGlarLixi Fixed-Ratio Combination in the Treatment of Type 2 Diabetes: A Narrative Review.
iGlarLixi is a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide used in the treatment of type 2 diabetes. iGlarLixi has proven clinical benefits in terms of glycemia, weight control, and safety, defined by the risk of hypoglycemia. It simultaneously targets many pathophysiologic abnormalities which are at the root of type 2 diabetes and thus presents a complementary mode of action. Finally, it may also address diabetes treatment burden, and, by decreasing the complexity of treatment, it may improve patient adherence and persistence and fight against clinical inertia. This article reviews the results of major randomized controlled trials in people with type 2 diabetes that compared iGlarLixi to other therapeutic regimens, representing different intensification strategies, such as basal supported oral therapy, oral antidiabetic drugs, and a combination of the latter with glucagon-like peptide 1 receptor agonists. Moreover, as a supplement to randomized trials, data from real-world evidence have also been included.


Elucidating interactive effects of sulfidated nanoscale zero-valent iron and ammonia on anaerobic digestion of food waste.
In our previous study, anaerobic digestion of food waste could be effectively enhanced by adding sulfidated nanoscale zero-valent iron (S-nZVI) under high-strength ammonia concentrations. In this study, in order to further elucidate the specific interactive effects of S-nZVI and ammonia on anaerobic digestion of nitrogen-rich food waste, the methanogenic performance of anaerobic digestion systems respectively added with nanoscale zero-valent iron (nZVI) and S-nZVI were compared and monitored under different ammonia stress conditions. Both nZVI and S-nZVI could effectively stimulate the methanogenesis process among ammonia concentrations ranging from 0 to 3500 mg/L. However, the enhancing effects of S-nZVI and nZVI on anaerobic digestion of food waste were different, in which anaerobic digestion systems added with S-nZVI and nZVI performed best under 2500 mg/L of ammonia and 1500 mg/L of ammonia, respectively. Furthermore, the analysis of microbial communities suggested that ammonia stress enriched acetoclastic methanogens, while adding nZVI and S-nZVI into anaerobic digestions stimulated the process of hydrogenotrophic methanogenesis. Moreover, S-nZVI performed better in promoting the evolution of DIET-related microorganisms than nZVI, resulting in enhanced methane production under high ammonia-stressed conditions. This work provided fundamental knowledge about the interactive effects of S-nZVI and ammonia on the anaerobic digestion of food waste.


Nontyphoid salmonella infection: microbiology, clinical features, and antimicrobial therapy.
Nontyphoid Salmonella is the most common bacterial pathogen causing gastrointestinal infection worldwide. Most nontyphoid Salmonella infection is limited to uncomplicated gastroenteritis that seldom requires antimicrobial treatment. Nevertheless, invasive infections, such as bacteremia, osteomyelitis, and meningitis, may occur and require antimicrobial therapy. Continuous genetic and genomic evolution in Salmonella leading to increased virulence and resistance to multiple drugs are of significant public health concern. Two major changes in the epidemiology of nontyphoid salmonellosis in Europe and in the USA occurred in the second half of the 20(th) century: the emergence of foodborne human infections caused by Salmonella enterica serotype Enteriditis and by multidrug-resistant strains of Salmonella enterica serotype Typhimurium. In the 21(st) century, a worsening situation is the increasing resistance to fluoroquinolones and third-generation cephalosporins in nontyphoid Salmonella. Clinical isolates showing carbapenem resistance also have been identified. Although antimicrobial therapy is usually not indicated for uncomplicated Salmonella gastroenteritis, recent studies indicated that a short-course ceftriaxone therapy (3-5 days) for patients with severe gastroenteritis would lead to a faster clinical recovery. Continuous surveillance of Salmonella in both humans and animals is mandatory. A better understanding of the mechanisms that lead to the emergence of antimicrobial resistance in Salmonella may help in the devising of better interventional strategies to reduce the spread of resistant Salmonella between humans and reservoirs along the food chain.


Immunological identification of four different polypeptides in 'subunit VII' of mammalian cytochrome c oxidase.
Rat liver cytochrome c oxidase was separated by SDS-gel electrophoresis into 13 polypeptide bands. Monospecific antisera against the isolated polypeptides VIIa, VIIb and VIIc were raised in rabbits. Cytochrome c oxidase was blotted on nitrocellulose and incubated with the antisera. The antisera reacted only with their corresponding polypeptides, indicating no immunological relationship between polypeptides VIIa, VIIb and VIIc. The data also exclude that these polypeptides are proteolytic breakdown products of larger subunits.


The nurse-patient relationship and victims of violence.
Vicarious traumatization is a phenomenon that recognizes that the exposure of persons, other than the victim, to the specifics of trauma material or the reenactment of traumatic experiences transmits the emotionally laden aspects of the original violence and thus is a source of emotional arousal and distress for the nurse working with victims of violence. This source of emotional arousal shapes the underlying approach--avoidance dynamic of countertransference responses that strain the empathic connection necessary for a safe and constructive nurse-patient relationship. Case consultation and supervision are necessary to protect the integrity of the nurse-patient relationship. The current isolating changes in the work setting cut the nurse off from needed support and guidance in working with victims of violence. The emotional risks inherent in working with victims of violence require that the nurse seek professional support for the interpersonal aspects of practice.


Flexible genosensors based on polypyrrole and graphene quantum dots for PML/RARα fusion gene detection: A study of acute promyelocytic leukemia in children.
Acute promyelocytic leukemia (APL) in children is associated with a favorable initial prognosis. However, minimal residual disease (MRD) follow-up remains poorly defined, and relapse cases are concerning due to their recurrent nature. Thus, we report two electrochemical flexible genosensors based on polypyrrole (PPy) and graphene quantum dots (GQDs) for label-free PML-RARα oncogene detection. Atomic force microscopy (AFM), scanning electron microscope (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were used to characterize the technological biosensor development. M7 and APLB oligonucleotide sequences were used as bioreceptors to detect oncogenic segments on chromosomes 15 and 17, respectively. AFM characterization revealed heterogeneous topographical surfaces with maximum height peaks for sensor layers when tested with positive patient samples. APLB/Genosensor exhibited a percentage change in anode peak current (ΔI) of 423 %. M7/Genosensor exhibited a ΔI of 61.44 % for more concentrated cDNA samples. The described behavior is associated with the biospecific recognition of the proposed biosensors. Limits of detection (LOD) of 0.214 pM and 0.677 pM were obtained for APLB/Genosensor and M7/Genosensor, respectively. The limits of quantification (LOQ) of 0.648 pM and 2.05 pM were estimated for APLB/Genosensor and M7/Genosensor, respectively. The genosensors showed reproducibility with a relative standard deviation of 7.12 % for APLB and 1.18 % for M7 and high repeatability (9.89 % for APLB and 1.51 % for M7). In addition, genetic tools could identify the PML-RARα oncogene in purified samples, plasmids, and clinical specimens from pediatric patients diagnosed with APL with high bioanalytical performance. Therefore, biosensors represent a valuable alternative for the clinical diagnosis of APL and monitoring of MRD with an impact on public health.


Postnatal exposure to trimethyltin chloride induces retinal developmental neurotoxicity in mice via glutamate and its transporter related changes.
Exposure to toxic substances during postnatal period is one of the major factors causing retinal developmental defects. The developmental toxicity of trimethyltin chloride (TMT), a byproduct of an organotin compound widely used in agriculture and industrial fields, has been reported; however, the effect on the mammalian retina during postnatal development and the mechanism have not been elucidated to date. We exposed 0.75 and 1.5 mg/kg of TMT to neonatal ICR mice (1:1 ratio of male and female) up to postnatal day 14 and performed analysis of the retina: histopathology, apoptosis, electrophysiological function, glutamate concentration, gene expression, and fluorescence immunostaining. Exposure to TMT caused delayed eye opening, eye growth defect and thinning of retinal layer. In addition, apoptosis occurred in the retina along with b-wave and spiking activity changes in the micro-electroretinogram. These changes were accompanied by an increase in the concentration of glutamate, upregulation of astrocyte-related genes, and increased expression of glial excitatory amino acid transporter (EAAT) 1 and 2. Conversely, EAAT 3, 4, and 5, mainly located in the neurons, were decreased. Our results are the first to prove postnatal retinal developmental neurotoxicity of TMT at the mammalian model and analyze the molecular, functional as well as morphological aspects to elucidate possible mechanisms: glutamate toxicity with EAAT expression changes. These mechanisms may suggest not only a strategy to treat but also a clue to prevent postnatal retina developmental toxicity of toxic substances.


Relationship of the lipopolysaccharide structure of Yersinia pestis to resistance to antimicrobial factors.
Disruption of lipopolysaccharide (LPS) biosynthesis genes in an epidemiologically significant Yersinia pestis strain showed that the ability to synthesize the full inner core of the LPS is crucial for resistances to the bactericidal action of antimicrobial peptides and to complement-mediated serum killing. Resistance to polymyxin B also requires a high content of the cationic sugar, 4-amino-4-deoxy-L-arabinose, in lipid A.


Liver-directed gene therapy using the sleeping beauty transposon system.
Sleeping Beauty (SB) is a transposon system genetically reconstructed from teleost fish that mediates chromosomal integration of DNA sequences by a cut-and-paste mechanism. SB has been shown to mediate transposition in a variety of cells and tissues, has been used for the generation of transgenic animals and has been tested as a vector for gene therapy in several animal models of human disease. Here, we describe methods that we have developed for testing SB-mediated transposition, first in cultured mammalian cells, and then in vivo using a combination of rapid, high-volume tail vein injection for DNA delivery to the liver along with in vivo bioluminescence imaging to monitor sustained luciferase gene expression in individual animals.


Method validation and clinical utility of chromogenic factor VIII assay compared to one-stage assay.
The chromogenic FVIII assay is currently considered the gold standard for quantitation of factor VIII levels in both haemophilia A patients and as part of screening for thrombophilia. A method validation and evaluation of clinical utility within a routine diagnostic laboratory was undertaken by comparing the currently used one-stage assay to a commercially available chromogenic assay (Siemens, Johannesburg, South Africa). In total, 60 samples were included in this study to encompass the whole diagnostic range of the assay. Both low and high values showed very good correlation on linear regression analysis with correlation coeffients of 0.949 and 0.888 respectively. However, the lower detection limit of the Siemens Chromogenic assay was 1.5 IU/dL rendering it impossible to utilize in the setting of classifying a haemophilia A patient in terms of disease severity. Although the Siemens FVIII chromogenic assay shows excellent correlation to the currently used one-stage assay, the relatively high detection limit restrict implementation as a stand-alone assay in a routine diagnostic laboratory.


Plasma endothelin-1 as a marker for doxorubicin cardiotoxicity.
The use of doxorubicin is often limited by cardiotoxicity that can lead to congestive heart failure (CHF). Although various techniques have been used to predict its cardiotoxicity, none has proven useful. We reported 2 patients in whom the level of plasma endothelin (ET)-1 rose progressively during doxorubicin treatment of breast cancer, and who subsequently developed CHF. Accordingly, we conducted a prospective study of 30 consecutive patients, 23 with breast cancer and 7 with small-cell lung cancer, who were treated with doxorubicin. Serial changes in plasma ET-1 during doxorubicin treatment were measured by a specific radioimmunoassay, and plasma levels of atrial natriuretic peptide (ANP) were determined by a sensitive immunoradiometric assay. M-mode echocardiography was performed serially to monitor the fractional shortening (FS) and the left ventricular ejection fraction (LVEF). The plasma concentrations of ET-1 rose progressively in 5 of the 30 patients during doxorubicin treatment. Two of the 5 patients developed clinically overt CHF after developing cumulative doses of doxorubicin of 500 and 480 mg/m2. Serial measurement of plasma levels of ANP, FS and LVEF showed no abnormalities until the development of CHF. Another 25 patients who had received doxorubicin (cumulative doses ranging from 400 to 660 mg/m2) and had not developed CHF showed no appreciable change in plasma ET-1 or other markers. This prospective study suggests that plasma ET-1 may be useful for predicting the risk of doxorubicin-induced cardiotoxicity.


Diverging patterns of host use by phytophagous insects in relation to leaf pubescence in Arbutus xalapensis (Ericaceae).
Foliar pubescence in the mexican madrone (Arbutus xalapensis H.B.K.) is an extremely variable character. Leaf specimens of pilose and glabrous madrones showed a similar composition of major secondary compounds. On the other hand, sympatric pilose and glabrous individuals were found to support significantly different insect guilds. Insect preference was strongly associated to mouthpart anatomy. Chewing and gall-forming insects were significantly more abundant on glabrous trees while sucking insects were more common on pilose trees. Additionally, parasitation of sucking insects was lower on pilose trees, possibly because the plant trichomes provide protection against parasitoids.


On-going nitrification in chloraminated drinking water distribution system (DWDS) is conditioned by hydraulics and disinfection strategies.
Within the drinking water distribution system (DWDS) using chloramine as disinfectant, nitrification caused by nitrifying bacteria is increasingly becoming a concern as it poses a great challenge for maintaining water quality. To investigate efficient control strategies, operational conditions including hydraulic regimes and disinfectant scenarios were controlled within a flow cell experimental facility. Two test phases were conducted to investigate the effects on the extent of nitrification of three flow rates (Q = 2, 6, and 10 L/min) and four disinfection scenarios (total Cl2=1 mg/L, Cl2/NH3-N=3:1; total Cl2=1 mg/L, Cl2/NH3-N=5:1; total Cl2=5 mg/L, Cl2/NH3-N=3:1; and total Cl2=5 mg/L, Cl2/NH3-N=5:1). Physico-chemical parameters and nitrification indicators were monitored during the tests. The characteristics of biofilm extracellular polymetric substance (EPS) were evaluated after the experiment. The main results from the study indicate that nitrification is affected by hydraulic conditions and the process tends to be severe when the fluid flow transforms from laminar to turbulent (2300<Re<4000). Increasing disinfectant concentration and optimizing Cl2/NH3-N mass ratio were found to inhibit nitrification to some extend when the system was running at turbulent condition (Q = 10 L/min, Re = 5535). EPS extracted from biofilm that was established at the flow rate of 6 L/min had greater carbohydrate/protein ratio. Furthermore, several nitrification indicators were evaluated for their prediction efficiency and the results suggest that the change of nitrite, together with total organic carbon (TOC) and turbidity can indicate nitrification potential efficiently.


Stable quasi-solid-state lithium-organic battery based on composite gel polymer electrolyte and compatible organic cathode material.
High-performance organic small-molecule electrode materials are troubled with their high solubility in liquid electrolytes. The construction of quasi-solid-state lithium organic batteries (LOBs) using gel polymer electrolytes with high mechanical properties, compromised ionic conductivity, high safety, and eco-friendly is an effective way to inhibit the dissolution of active materials. Herein, two hexaazatriphenylene (HATN)-based organic cathode materials (HATNA-6OCH3 and HATNA-6OH) are synthesized and then matched with polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP)-based gel polymer electrolytes to construct quasi-solid-state LOBs. Thanks to the enhanced interfacial compatibility between organic cathode material and gel polymer electrolyte, HATNA-6OH with compatible hydroxyl group shows the enhanced electrochemical properties compared with HATNA-6OCH3. Further, the electrochemical performance is improved when HATNA-6OH is combined with a gel polymer electrolyte modified with a succinonitrile (SN) plasticizer (GPE-0.4SN), including a high specific capacity of 153.3 mAh g-1 at 50 mA g-1 and a good reversible capacity of 88 mAh g-1 after 100 cycles at 200 mA g-1. In addition, the good electrochemical properties and lithium-ion storage mechanism of HATNA-6OH have been elucidated using density functional theory (DFT) and spectral characterizations.