Numerical simulation of the nonlinear ultrasonic pressure wave propagation in a cavitating bubbly liquid inside a sonochemical reactor.
We investigate the acoustic wave propagation in bubbly liquid inside a pilot sonochemical reactor which aims to produce antibacterial medical textile fabrics by coating the textile with ZnO or CuO nanoparticles. Computational models on acoustic propagation are developed in order to aid the design procedures. The acoustic pressure wave propagation in the sonoreactor is simulated by solving the Helmholtz equation using a meshless numerical method. The paper implements both the state-of-the-art linear model and a nonlinear wave propagation model recently introduced by Louisnard (2012), and presents a novel iterative solution procedure for the nonlinear propagation model which can be implemented using any numerical method and/or programming tool. Comparative results regarding both the linear and the nonlinear wave propagation are shown. Effects of bubble size distribution and bubble volume fraction on the acoustic wave propagation are discussed in detail. The simulations demonstrate that the nonlinear model successfully captures the realistic spatial distribution of the cavitation zones and the associated acoustic pressure amplitudes.


Complex surgical reconstruction for spinopelvic instability caused by a giant Tarlov cyst eroding the sacrum: A case report.
Tarlov cysts (TC), also known as perineural cysts are meningeal dilations of the posterior nerve root sheath that typically affect sacral nerve roots. TC are usually asymptomatic and found incidentally. We present the case of a patient with an enlarging sacral TC causing pain from spinopelvic instability secondary to extensive bone erosion. Such illustrative case is intended to increase awareness of the potential need for complex spinopelvic reconstruction in atypical instances of large TC. A 29-year-old female presented to clinic reporting progressive bilateral sacroiliac joint pain that was essentially mechanical in nature. The patient had a normal neurological exam except for a known left drop foot with numbness in the left sural nerve distribution, both attributed to a previously resected peripheral nerve sheath tumor. Magnetic resonance imaging revealed a large multilobulated lesion with imaging characteristics consistent with TC adjacent to the left side of the sacrum, extending outward from the left S1 and S2 neural foramina and measuring 6.7 × 3.7 cm in the axial plane and and 5.6 cm in the sagittal plane. Six weeks of conservative management consisting of physical therapy and pain management was unsuccessful, and the patient reported worsening pain. Surgical reconstruction consisting of L5-S1 transforaminal lumbar interbody fusion, L4 to pelvis navigation-guided instrumentation and posterolateral fusion, and bilateral sacroiliac joint fusion was successfully performed. At 12 weeks follow-up appointment after surgery, the patient reported resolution of sacroiliac mechanical pain. Sacral TC are asymptomatic in their vast majority of cases but may occasionally cause neurological deficits secondary to mass effect. Rarely, however, giant TC can also lead to significant bone erosion or the sacrum with secondary spinopelvic instability. In this brief report, we describe a giant TC generating significant spinopelvic instability, which was successfully treated with complex spinopelvic reconstruction, leading to complete resolution of the reported axial mechanical pain.


Roles of helicases in translation initiation: a mechanistic view.
The goal of this review is to summarize our current knowledge about the helicases involved in translation initiation and their roles in both general and mRNA-specific translation. The main topics covered are the mechanisms of helicase action, with emphasis on the roles of accessory domains and proteins; the functions performed by helicases in translation initiation; and the interplay between direct and indirect effects of helicases that also function in steps preceding translation initiation. Special attention is given to the dynamics of eIF4A binding and dissociation from eIF4F during mRNA unwinding. It is proposed that DHX29, as well as other helicases and translation initiation factors could also cycle on and off the translation initiation complexes, similar to eIF4A. The evidence in favor of this hypothesis and its possible implications for the mechanisms of translation initiation is discussed. This article is part of a Special Issue entitled: The biology of RNA helicases - Modulation for life.


Breast cancer, stem cells and prospects for therapy.
The mammary epithelium contains multipotent stem cells that give rise to all differentiated cell types present within the tissue. Mammary epithelial stem cells have been prospectively purified from dissociated mammary epithelium on the basis of cell surface antigen expression. It has become apparent in recent years that for breast cancer and other malignancies only a small proportion of tumour cells--'cancer stem cells'--have the capacity for extensive proliferation and transferral of the tumour. We review the evidence for breast cancer stem cells, we consider their relationship to mammary epithelial stem cells and we examine the implications for current and future therapeutic strategies.


TGFβ1 Leu10Pro polymorphism contributes to the development of prostate cancer: evidence from a meta-analysis.
Transforming growth factor-β1 (TGFβ1) plays a significant role in regulating cellular proliferation and apoptosis. A large number of studies related to the association between TGFβ1 Leu10Pro polymorphism and prostate cancer (PC) risk, but get conflicting results. We performed a meta-analysis based on six studies, assessing the strength of the association using odds ratios (OR) with 95% confidence intervals (CI). Overall, our evidence has indicated that TGFβ1 Leu10Pro polymorphism had significantly increased PC risk in the allele comparison model (OR = 1.081, 95% CI = 1.003-1.165, Pheterogeneity = 0.141, P = 0.041). In the stratified analysis by ethnicity, the same results were found among Caucasians (for heterozygote model, OR = 1.741, 95% CI = 1.004-3.020, Pheterogeneity = 0.000, P = 0.049; recessive model, OR = 1.339, 95% CI = 1.045-1.717, Pheterogeneity = 0.020, P = 0.021; allele comparison model, OR = 1.091, 95% CI = 1.005-1.184, Pheterogeneity = 0.048, P = 0.037). In conclusion, this meta-analysis suggested that TGFβ1 Leu10Pro polymorphism contributed to the development of PC. A well-designed and larger study is still required to evaluate this polymorphism and PC risk.


Feeding by seed bugs and weevils enhances germination of wild Gossypium species.
Seeds of Gossypium sturtianum and G. thurberi do not readily germinate under most conditions. Increased germination of G. sturtianum was associated in nature with the presence of a seed bug, Oxycarenus luctuosus. Experimental and descriptive studies were conducted in Australia and Arizona to test the hypothesis that more seeds of G. sturtianum and G. thurberi germinated during their first wet season from bolls that had been attacked by insects than from unattacked bools. In Australia, seeds from G. sturtianum bolls that had been caged with O. luctuosus were more likely to germinate than those caged without bugs. In Arizona USA, seeds of G. thurberi were attacked by boll weevils, Anthonomus grandis, and seed bugs, Sphyrocoris punctellus. Weevils destroyed 21%, scarified another 26%, and left undamaged the remaining 53% of the seeds in attacked bolls. Seeds of G. thurberi from bolls with weevils and seed bugs that were not destroyed by these insects were more likely to germinate during their first wet season than seeds from unattacked bolls. All three insects probably increase germination by breaking the impermeable seed coat. The ecological and evolutionary consequences of this interaction are not known.


Risk of late-onset adhesions and incisional hernia repairs after surgery.
Long-term adhesion-related complications and incisional hernias after abdominal surgery are common and costly. There are few data on the risk of these complications after different abdominal operations. We identified Medicare beneficiaries who underwent endovascular repair of an abdominal aortic aneurysm from 2001-2008 who presumably are not at risk for laparotomy-related complications. We identified all laparoscopic and open operations involving the abdomen, pelvis, or retroperitoneum and categorized them into 5 groups according to invasiveness. We then identified laparotomy-related complications for up to 5 years after the index operation and compared these with the baseline rate of complications in a control group of patients who did not undergo an abdominal operation. We studied 85,663 patients, 7,513 (8.8%) of which underwent a laparotomy, including 2,783 major abdominal operations, 709 minor abdominal operations, 963 ventral hernia repairs, 493 retroperitoneal/pelvic operations, and 2,565 laparoscopic operations. Mean age was 76.7 years and 82.0% were male. Major abdominal operations carried the highest risk for adhesion-related complications (14.3% and 25.0% at 2 and 5 years compared with 4.0% and 7.8% for the control group; p < 0.001) and incisional hernias (7.8% and 12.0% compared with 0.6% and 1.2% for the control group; p < 0.001). Laparoscopic operations (4.6% and 10.7% for adhesions, 1.9% and 3.2% for incisional hernias) carried the lowest risk. Late-onset laparotomy-related complications are frequent and their risk extends through 5 years beyond the perioperative period. With the advancement and expansion of laparoscopic techniques and its attendant lower risk for long-term complications, these results can alter the risk-to-benefit profile of various types of abdominal operations and can also strengthen the rationale for additional development of laparoscopic approaches to abdominal operations.


Mucosal immunization with recombinant MOMP genetically linked with modified cholera toxin confers protection against Chlamydia trachomatis infection.
Chlamydia trachomatis is a major human health pathogen due to its role in sexually transmitted diseases. Thus, there is a need to develop an effective vaccine at the mucosal surface against this pathogen. In an effort to develop a mucosal vaccine, a modified cholera toxin gene was genetically linked to the C. trachomatis MoPn NiggII MOMP gene to generate a recombinant protein with the mucosal adjuvant properties of the cholera toxin and immunological antigenicity of the chlamydial protein. The recombinant fusion protein (rMOMP) was expressed in E. coli, purified and analyzed by SDS-PAGE, immunoblot, and GM1-ELISA, and subsequently used to immunize BALB/c mice via intranasal (i.n.) and intravaginal (vag.) routes. The rMOMP protein administered via the i.n. route induced a higher concentration of anti-MOMP specific antibodies in both serum and vaginal washes as compared to mice immunized with Chlamydia or PBS. Antibody isotype analysis revealed that i.n. administration of rMOMP to mice induced higher concentrations of serum and vaginal wash IgA, IgG1, IgG2a, and IgG2b antibodies. Vaginal washes from all immunized mice following a chlamydial challenge infection were analyzed by indirect immunoflourescence to study the level of protection provided by various immunogens. Maximum protection against C. trachomatis as assessed by reduction in C. trachomatis inclusion forming units (IFU) was provided by i.n. immunization of mice with rMOMP. This is a first report using genetic fusion of cholera toxin and MOMP genes and provides a novel approach for the design and development of a mucosal vaccine against Chlamydia.


Usutu virus in cerebrospinal fluid: A 2-year survey in a Tertiary Care Hospital, Geneva, Switzerland.
In 2009, the Usutu virus (USUV) was first reported as a cause of human neuroinvasive disorders. In Switzerland, USUV has been detected in wild birds with a seroprevalence of up to 6.59% in captive specimens sampled from zoo enclosures. This study investigates the clinical prevalence of USUV in human acute neuroinvasive disorders in Switzerland. Two hundred and fifty-eight cerebrospinal fluid samples collected between 2015 and 2017 for routine clinical care in a tertiary level hospital (Geneva) were tested for USUV by rRT-PCR. No samples were found positive, suggesting the absence, or the extremely low circulation of USUV in Western Switzerland.


Hypoxic preconditioning protects cardiomyocytes against hypoxia/reoxygenation-induced cell apoptosis via sphingosine kinase 2 and FAK/AKT pathway.
Previous studies have demonstrated that hypoxic preconditioning (HPC) alleviates hypoxia/reoxygenation (H/R) injury. However, the impact and mechanism involved were not fully understood. This study aimed to evaluate the effect of HPC on H/R injury in cardiomyocytes and investigate the molecular mechanisms involved. In our study, primary neonatal rat cardiomyocytes were isolated and characterized by immunofluorescence staining. We established H/R models in vitro to mimic ischemia/reperfusion (I/R) injury in vivo. Primary cardiomyocytes were exposed to HPC and then subjected to H/R. SphK2 expression was determined by quantitative real-time PCR and Western blotting. Cell apoptosis was measured by Hoechst staining. H9c2 cells were transfected with SphK2 siRNA or pcDNA3.1-SphK2 plasmid. The transfection efficiency was evaluated 48h post-transfection. After H/R, cell apoptosis rate was determined by Annexin V-FITC/PI and caspase-3/-9 activity was measured. The activation of FAK/AKT pathway was evaluated by Western blotting. Our results showed that HPC significantly increased SphK2 expression in primary cardiomyocytes under normal or H/R condition and protected against H/R-induced cell apoptosis, whereas SphK2 inhibitor K145 abolished the cardioprotective effect of HPC. HPC markedly reduced the cell apoptosis rate of H9c2, decreased the activities of caspase-3 and -9 and increased p-FAK and p-AKT levels, which were reversed by SphK2 knockdown. Additionally, SphK2 overexpression exerted a similar effect with HPC on cell apoptosis and FAK/AKT. Inhibition of H9c2 cell apoptosis induced by HPC and SphK2 overexpression was abolished by PI3K/AKT inhibitor LY294002. These results indicate that HPC may protect cardiomyocytes against H/R injury via SphK2 and the downstream FAK/AKT signaling pathway. Our findings provided important evidences for the protective role of HPC in ameliorating myocardial H/R injury.


Broad diversity in monoterpene-sesquiterpene balance across wild sunflowers: Implications of leaf and floral volatiles for biotic interactions.
As plant lineages diversify across environmental gradients, species are predicted to encounter divergent biotic pressures. This study investigated the evolution of volatile secondary metabolism across species of Helianthus. Leaves and petals of 40 species of wild Helianthus were analyzed via gas chromatography-mass spectrometry to determine volatile secondary metabolite profiles. Across all species, 500 compounds were identified; 40% were sesquiterpenes, 18% monoterpenes, 3% diterpenes, 4% fatty acid derivatives, and 35% other compounds such as phenolics and small organic molecules. Qualitatively, annuals and species from more arid western climates had leaf compositions with a higher proportion of total monoterpenes, while erect perennials and species from more mesic eastern habitats contained a higher proportion of total sesquiterpenes. Among species, mass-based leaf monoterpene and sesquiterpene abundance were identified as largely orthogonal axes of variation by principal component analysis. Profiles for leaves were not strongly correlated with those of petals. Volatile metabolites were highly diverse among wild Helianthus, indicating the value of this genus as a model system and rich genetic resource. The independence of leaf and petal volatile profiles indicates a low level of phenotypic integration between vegetative and reproductive structures, implying vegetative defense and reproductive defense or pollinator attraction functions mediated by terpene profiles in these two organs can evolve without major trade-offs. The major biosynthetic pathways for the major terpenes in wild Helianthus are already well described, providing a road map to deeper inquiry into the drivers of this diversity.


A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder.
To perform a systematic review of the health-related quality of life (HRQoL) and economic burdens of anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). A systematic literature search of English-language studies was performed in Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier, and Cochrane Library. Cost data were converted to 2014 Euro. Sixty-nine studies were included. Data on HRQoL were reported in 41 studies (18 for AN, 17 for BN, and 18 for BED), on healthcare utilization in 20 studies (14 for AN, 12 for BN, and 8 for BED), and on healthcare costs in 17 studies (9 for AN, 11 for BN, and only 2 for BED). Patients' HRQoL was significantly worse with AN, BN, and BED compared with healthy populations. AN, BN, and BED were associated with a high rate of hospitalization, outpatient care, and emergency department visits. However, patients rarely received specific treatment for their eating disorder. The annual healthcare costs for AN, BN, and BED were €2993 to €55,270, €888 to €18,823, and €1762 to €2902, respectively. AN, BN, and BED have a serious impact on patient's HRQoL and are also associated with increased healthcare utilization and healthcare costs. The burden of BED should be examined separately from that of BN. The limited evidence suggests that further research is warranted to better understand the differences in long-term HRQoL and economic burdens of AN, BN, and BED.


Bilateral nephroblastoma in a horseshoe kidney.
A case of bilateral nephroblastoma in a horseshoe kidney is presented. It is the second to be reported in the international literature.


Light-induced modifications of DNA by gilvocarcin V and its aglycone.
Gilvocarcins are antitumor agents that have been reported to damage DNA upon activation by visible light. This activation is dependent on interaction with DNA. Here it is shown that gilvocarcin V and its synthetic aglycone analogue can both introduce single-strand scission into plasmid DNA. Light irradiation is required for the reaction. The binding of gilvocarcin V to plasmid DNA in the absence of light decreased the DNA linking number in a fashion similar to known intercalating agents such as ethidium bromide. The use of oligonucleotides as substrates for gilvocarcin V demonstrated that one of the steps of the reaction following binding of gilvocarcin V to DNA involves covalent modification at thymidine and to a lesser extent, cytosine residues.


An infrequent relapse of multiple myeloma predominantly manifesting as light chain escape: clinical experience from two Chinese centers.
Patients with intact immunoglobulin (Ig) multiple myeloma (MM) usually show parallel fluctuations of their intact Ig and light chain (LC) concentrations. Herein we report 11 patients with relapsed, intact Ig MM with a marked increase in urinary LCs in the absence of a parallel rise in serum intact Ig, known as light chain escape (LCE). A major feature accompanying the presentation of LCE was conversion of plasma cell morphology. An important feature preceding the onset of LCE was the use of biological therapies. These patients were not associated with a highly aggressive course. Median overall survival times after the diagnosis of MM and after LCE were 48 months and 24 months, respectively. These cases represent a documented series of a rare but clinically important mode. More attention should be directed toward patients with intact Ig MM when the clinical course deteriorates despite a reduction of intact monoclonal immunoglobins.


Behavioral actions of baclofen in the rat ventromedial thalamic nucleus: antagonism by delta-aminovalerate.
Baclofen, an agonist at GABAB receptors injected locally into the rat ventromedial thalamic nucleus (VM) induced catalepsy in a dose-dependent, stereospecific and site-specific way. Baclofen-induced catalepsy was accompanied by tonic activity in the electromyogram (EMG) recorded from the gastrocnemius muscle, which is considered to be a measure of limb rigidity. delta-Aminovalerate (delta-AVA) coadministered with baclofen into the VM prevented the development of both catalepsy and limb rigidity. delta-AVA injected alone into the VM was devoid of depressant or stimulating behavioral effects. In contrast to delta-AVA, bicuculline, a GABAA antagonist, failed to antagonize baclofen-induced catalepsy. On the other hand, catalepsy due to local injection of a GABAA agonist, muscimol into the VM was antagonized by bicuculline, but not by delta-AVA. The present results suggest that delta-AVA may be useful as an antagonist of central pharmacological actions of baclofen.


Assessment of Aloe vera (L.) genotoxic potential on Escherichia coli and plasmid DNA.
Aloe vera is a tropical plant, known in Brazil as babosa and several reputable suppliers produce a stabilized aloe gel for topic use. Since people use Aloe vera topically, they could be exposed to solar ultraviolet light in addition and it might cause a cross damage effect between these agents. The aim of this work was to investigate the biological effects of Aloe vera pulp extract, associated or not to UVA radiation, on Escherichia coli-deficient repair mutants and plasmid DNA, in order to test its genotoxic potential. Data obtained from analysis of survival fractions, bacterial transformation and agarose gel electrophoresis suggest that Aloe vera has genotoxic properties, but it seems not to be able to damage the cell membrane.


Functional imaging evidence of the relationship between recurrent psychotic episodes and neurodegenerative course in schizophrenia.
It remains controversial as to what determines the neurodegenerative course in schizophrenia. This study administered a modified version of the Stroop task and investigated the relationship between functional magnetic resonance imaging (fMRI) signal changes in dysfunctioned task-related regions and clinical course variables. Functional MRI data during task performance were acquired from 10 right-handed schizophrenic patients (mean+/-SD age=29.2+/-10.3 years, range of illness duration=0.8-14 years, number of episodes=1-5) and 10 healthy controls (mean+/-SD age=30.3+/-6.4). Imaging data were investigated on a voxel-by-voxel basis for single group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM 99b). Correlation analysis with age as a covariate identified those brain regions whose fMRI signal changes were significantly related to clinical course variables in schizophrenia. The number of psychotic episodes was negatively correlated with the fMRI signal change in the right inferior frontal and the right frontal precentral gyri among the activated regions during the Stroop task in schizophrenia, whereas the length of illness was not so correlated. The number of psychotic episodes was also negatively correlated with the fMRI signal change in the left paracingulate in which functional activity was diminished in the patients relative to the controls. Our results indicate that recurrent psychotic episodes are related to the neurodegenerative course in some dysfunctional brain regions in schizophrenia.


Plant-based high internal phase emulsions stabilized by dual protein nanostructures with heat and freeze-thaw tolerance.
The formation of coherent, three-dimensional (3D) networks by particles either at the interface or in the bulk phase is vital for the stability of emulsions. In this study, nanoparticles of walnut proteins (WPs) were associated by unfolded fibrillar rice proteins (RPs), forming dual protein nanostructures (DPNs) characteristic of coherent 3D networks. The DPNs emulsified walnut oil and formed high internal phase emulsions (HIPEs), which were stable against 2-month storage and 30-min heating at 95 °C. Furthermore, the interfacial structures can be further reinforced by sodium chloride (50 mM and above), and became invulnerable to repeated freeze-thaw treatments. Based on the above results, a plant-based walnut sauce was developed with superior freeze-thaw stability to three arbitrary commercial mayonnaises. The HIPEs with tunable rheological properties in response to salt concentration and excellent stabilities against long-term storage, heating, and freeze-thaw may be potential surrogates of futuristic plant-based textural and sensory materials in foods.


Metal-Based Anticancer Complexes and p53: How Much Do We Know?
P53 plays a key role in protecting the human genome from DNA-related mutations; however, it is one of the most frequently mutated genes in cancer. The P53 family members p63 and p73 were also shown to play important roles in cancer development and progression. Currently, there are various organic molecules from different structural classes of compounds that could reactivate the function of wild-type p53, degrade or inhibit mutant p53, etc. It was shown that: (1) the function of the wild-type p53 protein was dependent on the presence of Zn atoms, and (2) Zn supplementation restored the altered conformation of the mutant p53 protein. This prompted us to question whether the dependence of p53 on Zn and other metals might be used as a cancer vulnerability. This review article focuses on the role of different metals in the structure and function of p53, as well as discusses the effects of metal complexes based on Zn, Cu, Fe, Ru, Au, Ag, Pd, Pt, Ir, V, Mo, Bi and Sn on the p53 protein and p53-associated signaling.


Global research output in 'pharmacovigilance' during 2010-2020.
The rapid spread of Covid-19 pandemic globally has thrust drugs safety into the spotlight and the public is now more aware of the role of healthcare professionals and health regulators. The present study aimed to measure the global research landscape on pharmacovigilance (PV) indexed in Scopus database for eleven years period spanning from 2010-2020. The study has sought to use quantitative and visualization technologies for data analysis and interpretation. The search strategy accumulated a total of 2052 global publications data on PV. The findings disclose that the global research productivity on PV registered 8.74% average growth rate (AGR) and 7.38% compound average growth rate (CAGR). The mean relative growth rate (RGR) and doubling time (DT) of PV global publications for the 11 years is 0.27 and 3.03, respectively. The average number of authors per paper (AAPP) is 1.52 and average productivity per author (PPA) is 0.68. The authorship patterns in PV research shows collaborative trend as most of the publications have been published by multiple authors (80.75%). The mean values of degree of collaboration (DC), collaboration index (CI), collaboration coefficient (CC) and modified collaboration coefficient (MCC) during the selected period of study are 0.79, 2.74, 0.72, and 0.73, respectively which highly significant and indicates the better authorship collaborations. France is the bellwether in PV related scientific research as produced the highest number of publications.


Back to the bedside. Teaching on nursing rounds.
1. Teaching at the bedside provides the means for nursing students to begin their professional contacts with patients. 2. Teaching at the bedside should begin with selecting patients who illustrate specific problems and obtaining their consent. 3. Connoisseurship in clinical teaching means knowing and appreciating what is clinically significant at the bedside. 4. After teaching at the bedside, it is important to debrief students.


The first case of genetically confirmed sparganosis (Spirometra erinaceieuropaei) in European reptiles.
Sparganosis is a zoonosis caused by the spargana (larvae) of Spirometra sp. (Diphyllobothriidae). Reptiles are particularly important vectors for the transmission of this parasite in Asia; however, their role in sparganosis spread in European wildlife is unrecognized. We investigated the infection of reptiles with Spirometra sp. in NE Poland, where several mammalian hosts have been identified recently and in the past. Of the 59 dead reptiles, plerocercoids were found in two grass snakes (Natrix natrix) from the Białowieża Primeval Forest (BPF). The Spirometra erinaceieuropaei species was genetically confirmed using the evolutionary conserved nuclear 18S rRNA gene, and then compared to GenBank deposits. The sequences were identical to previously investigated Spirometra sp. found in Eurasian badger and wild boar from BPF. Our finding is the first genetically confirmed record of Spirometra sp. in reptiles in Europe. Since reptiles are often a component of mammalian diet, they can be a source of Spirometra tapeworm infection in European wildlife; however, further studies are needed to investigate the prevalence of infection in reptiles and other non-mammalian hosts.


Driving automation state-of-mind: Using training to instigate rapid mental model development.
The automotive industry is chugging along towards full autonomy, with a yet unknown time of arrival. The next call, however, is partial driving automation. At this interim station lurks many dangers, there-among them issues surrounding the partial performance of the driving task. Despite their potential for increased safety, these systems come with many inherent limitations and caveats, and their safe use depend on drivers correctly understanding their new role. Training is proposed as a potentially effective method of introducing drivers to the central aspects in this human-automation interaction. A proof-of-concept training program designed to introduce drivers to a partial automation system was developed. The effects of training were then evaluated through a between-group mixed-methods simulator experiment. Results indicate that trained drivers both self-report and exhibit an improved understanding of the automation system. They also report a significantly higher inclination to retake control in critical situation, than do their untrained counterparts.


Kirner's deformity: progressiveness and classification.
In a 30-year-old man, bilateral Kirner's deformity has been diagnosed. In the fully extended finger, the long axes of the middle and terminal phalanges formed an angle of 10 degrees in the volar and 5 degrees in the radial direction. Owing to the altered morphology of the distal phalanx, its palmar surface was at an angle of 25 degrees to the long axis of the middle phalanx. The deformity has existed since birth and has not changed except in size. His mother had the same bilateral deformity. Other closer relatives showed a unilateral appearance of Kirner's deformity: his maternal grandmother and an uncle had in their right little finger and an aunt had in her left little finger. Although some authors reported that Kirner's deformity was progressive, the description only referred to a change in the deformity. Kirner's deformity may be classified according to its period of onset, i.e., a more frequently occurring early type and a late type of onset (with lower incidence) exists. Moreover, it can be further classified by typical morphologic changes as well as the family history of the affected person.


A micromethod for absorption of specific antibody using an enzyme-linked immunosorbent assay (ELISA).
A procedure for absorbing specific antibodies using an enzyme-linked immunosorbent assay system (ELISA) has been developed. This is accomplished by serial absorption of the serum using less than 20 micrograms antigen. The sera can then be used in an ELISA system to test reactivity with other antigens. The system was tested by absorbing anti-myelin or anti-cerebroside antibodies and comparing these results with bulk absorption.


Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula.
Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey's method, a modified method based on derivatization with Mosher's reagents and analysis using LC-MS, and the use of (3)J(H-H) coupling constant values, were utilized for the determination of its absolute configuration. Compound 1 is related to the aurilide-class of molecules and it differs mainly in the macrocyclic structure by having a 27 membered ring system due to additional methylene carbon in the polyketide moiety. Lagunamide C displayed potent cytotoxic activity against a panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC(50) values ranging from 2.1 nM to 24.4 nM. Compound 1 also displayed significant antimalarial activity with IC(50) value of 0.29 μM when tested against Plasmodium falciparum. In addition, lagunamide C exhibited weak anti-swarming activity when tested at 100 ppm against the Gram-negative bacterial strain, Pseudomonas aeruginosa PA01.


Comparison of A-block polydispersity effects on BAB triblock and AB diblock copolymer melts.
Recent experiments on triblock copolymer melts suggest that polydispersity effects are dramatically enhanced when polydisperse blocks are constrained by both ends to the internal interfaces of an ordered morphology. To quantify the relevance of architecture, we compare BAB triblock and AB diblock copolymer melts with polydisperse A blocks and monodisperse B blocks, using self-consistent field theory (SCFT). We do, in fact, find an enhanced shift in the order-order transitions (OOTs) of the triblock copolymer system in good agreement with the experiments, which we attribute to a reduction of entropy in the A-rich domains due to the absence of chain ends. There is also a slightly enhanced dilation of the domains, but not nearly to the same degree as reported by the experiments. Unlike in the experiments, our calculations indicate that the polydispersity-induced shifts in the order-disorder transition (ODT) should be quantitatively similar for both diblocks and triblocks. It is possible that some of the pronounced effects observed in the experiments have more to do with the detailed shape of the molecular-weight distribution than the triblock architecture.


[Transcanalicular Laser Dacryocystorhinostomy: One-Year-Experience in the Treatment of Acquired Nasolacrimal Duct Obstructions].
External dacryocystorhinostomy (DCR) is at present the gold standard for the surgical treatment of acquired nasolacrimal duct obstructions, but tremendous progress has been made in recent years in improving minimally invasive techniques, sparing not only the skin, but also the medial lid structures, which contribute to the physiological palpebral-canalicular pump mechanism. The purpose of this study is to report our 1-year experience with the surgical technique, complications and results of transcanalicular laser assisted DCR. 48 consecutive transcanalicular laser-assisted DCRs combined with bicanalicular silicone intubation were performed for acquired nasolacrimal duct obstruction, and evaluated for intra- and postoperative complications, as well as subjective and objective success rates. Transcanalicular laser-assisted DCR combined with bicanalicular silicone intubation was surgically feasible in 45 cases (94 %). In 3 patients (6 %) it was impossible to position the aiming beam correctly at the anteroinferior rim of the middle turbinate using the superior canalicular approach, due to superior orbital rim prominence. Therefore 2 patients received no silicone intubation, despite a patent osteotomy at the back of the middle turbinate, and 1 patient underwent intraoperative conversion to external DCR due to anatomical narrowness of the nasal cavity. Perioperatively, 1 patient developed canalicular infection, 1 patient exhibited thermal injury to the canaliculus, and 4 patients exhibited premature prolapse of the silicone tube. At 6-months follow-up, functional success--defined as resolution of preoperative symptoms--was achieved in 35 of 45 surgically successful transcanalicular laser-assisted DCRs (78 %). Of the 10 postoperative failures (22 %), all patients reported epiphora, 6 patients were unable to irrigate the lacrimal drainage system, and 6 patients required surgical revision using external DCR. Transcanalicular laser assisted DCR is a promising minimally invasive approach for the surgical treatment of acquired nasolacrimal duct obstruction, in order to fill the gap between recanalising first step procedures and external DCR.


Gender differences in farmers' responses to climate change adaptation in Yongqiao District, China.
This study examines the gender differences in farmers' responses to climate change adaption in Yongqiao District, China. A random sampling technique was used to select 220 household heads, while descriptive statistics and binary logit models were used to analyze the data obtained from the households. We determine that male and female respondents are not significantly different in their knowledge and perceptions of climate change, but there is a gender difference in adopting climate change adaptation measures. Male-headed households are more likely to adopt new technology for water conservation and to increase investment in irrigation infrastructure. The research also indicates that the adaptation decisions of male and female heads are influenced by different sets of factors. The findings of this research help to elucidate the determinants of climate change adaptation decisions for male and female-headed households and the strategic interventions necessary for effective adaptation.


Molecular mimicry between Larrea divaricata Cav. plant and a reference strain of Pseudomonas aeruginosa.
Currently, the world health sector faces a big problem due to the increase of bacterial strains resistant to antibiotics. In 2017, the World Health Organization reported a list of resistant bacteria, among which Pseudomonas aeruginosa was present. This opportunistic pathogen is associated to nosocomial infections, and no effective vaccines against this bacterium have been found. Larrea divaricata Cav. (jarilla) is a shrub highly distributed in America and widely used in folk medicine. In our laboratory, cross-reactivity of antibodies obtained from the recognition of jarilla proteins against proteins from gram-negative bacteria has been demonstrated. The objective of this study was to study the cross-reactivity of anti-L. divaricata antibodies with P. aeruginosa extracellular proteins in order to find an innocuous prophylactic therapy against this nosocomial pathogen. We observed that antibodies generated by proteins from jarilla crude extract recognized antigenic determinants present in extracellular proteins of P. aeruginosa. However, further studies are needed to investigate the neutralizing capacity of these antibodies on the specific enzymatic proteins involved in the pathogenicity of this bacterium.


Cerebral microbleeds and vascular cognitive impairment.
MRI manifestations of small vessel diseases including white matter hyperintensities and lacunes have been recognized as potential substrates of vascular cognitive impairment for many years. Cerebral microbleeds (CMBs)--small, perviascular haemorrhages seen as small, well-demarcated, hypointense, rounded lesions on MRI sequences sensitive to magnetic susceptibility effects--are also now recognized as an imaging marker for small vessel pathology, but their clinical impact on cognition remains uncertain. CMBs are present in about a third of patients with ischaemic stroke, and in a high proportion of patients with Alzheimer's disease, cerebral amyloid angiopathy, and vascular dementia. They have also been increasingly found in normal elderly populations, particularly using sequences optimized for their detection. Some recent studies have suggested an effect of CMBs on cognition, which could relate directly to focal damage to or dysfunction of adjacent brain tissues; alternatively, CMBs may be a more general marker for the severity of small vessel pathology related to hypertension or cerebral amyloid angiopathy. CMBs may therefore play a role in understanding the underlying mechanisms of vascular cognitive impairment, in diagnosis, and in assessing its severity and prognosis; this review considers recent evidence on this topic.


Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study.
Our aims were to investigate the treatment and clinicopathological variables in relation to prognosis in small cell neuroendocrine cervical carcinoma (SCNECC). Clinical data of SCNECC patients with International Federation of Gynaecology and Obstetrics (FIGO) stages I-IV treated between 1987 and 2009 at member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. Of the 179 eligible patients, 104 were of FIGO stage I, 19 stage IIA, 23 stage IIB, 9 stage III, and 24 stage IV. The median failure-free survival (FFS) was 16.0 months, and the median cancer-specific survival (CSS) was 24.8 months. In multivariate analysis, FIGO stage and lymph node metastasis were selected as independent variables in stages I-IV. In stages IIB-IVB, primary treatment containing etoposide and platinum for at least 5 cycles (EP5+) (n=16) was associated with significantly better 5-year FFS (42.9% versus 11.8%, p=0.041) and CSS (45.6% versus 17.1%, p=0.035) compared to other treatments (n=40). Furthermore, concurrent chemoradiation with EP5+ (CCRT-EP5+) was associated with even better 5-year FFS (62.5% versus 13.1%, p=0.025) and CSS (75.0% versus 16.9%, p=0.016). FIGO stage and lymph node metastasis are significant prognostic factors in SCNECC. In stages IIB-IVB, CCRT-EP5+ might be the treatment of choice, which could be also true for earlier stages. Despite limitations of a retrospective study spanning a long time period and heterogeneous managements, the results provide an important basis for designing future prospective studies.


Potentiation of the respiratory burst of human neutrophils by cycloheximide: regulation of reactive oxidant production by a protein(s) with rapid turnover?
Incubation of human neutrophils with the protein biosynthesis inhibitor cycloheximide for > or = 90 min results in a decreased ability to generate reactive oxidants during the respiratory burst. This implies that active protein biosynthesis is required to sustain the ability of these cells to generate reactive oxidants. However, short term incubation of neutrophils (40-60 min) with either cycloheximide or puromycin results in a significant increase in oxidase activity stimulated by either fMet-Leu-Phe (> 60%) or by leukotriene B4 (> 30%). However, after incubation for 40-60 min with these inhibitors of protein biosynthesis, the respiratory burst stimulated by PMA was unaffected whilst that stimulated by the particulate stimuli opsonised zymosan or latex beads was significantly inhibited. The enhanced oxidase activity stimulated by the soluble agonists was not explained by changes in receptor expression, alterations in intracellular Ca2+ levels or by enhanced degranulation. These results suggest that oxidase activity stimulated by soluble agonists in neutrophils is normally regulated by a short-lived, actively-synthesised protein(s).


A multiparametric clinic-ultrasomics nomogram for predicting extremity soft-tissue tumor malignancy: a combined retrospective and prospective bicentric study.
We aimed at building and testing a multiparametric clinic-ultrasomics nomogram for prediction of malignant extremity soft-tissue tumors (ESTTs). This combined retrospective and prospective bicentric study assessed the performance of the multiparametric clinic-ultrasomics nomogram to predict the malignancy of ESTTs, when compared with a conventional clinic-radiologic nomogram. A dataset of grayscale ultrasound (US), color Doppler flow imaging (CDFI), and elastography images for 209 ESTTs were retrospectively enrolled from one hospital, and divided into the training and validation cohorts. A multiparametric ultrasomics signature was built based on multimodal ultrasomic features extracted from the grayscale US, CDFI, and elastography images of ESTTs in the training cohort. Another conventional radiologic score was built based on multimodal US features as interpreted by two experienced radiologists. Two nomograms that integrated clinical risk factors and the multiparameter ultrasomics signature or conventional radiologic score were respectively developed. Performance of the two nomograms was validated in the retrospective validation cohort, and tested in a prospective dataset of 51 ESTTs from the second hospital. The multiparametric ultrasomics signature was built based on seven grayscale ultrasomic features, three CDFI ultrasomic features, and one elastography ultrasomic feature. The conventional radiologic score was built based on five multimodal US characteristics. Predictive performance of the multiparametric clinic-ultrasomics nomogram was superior to that of the conventional clinic-radiologic nomogram in the training (area under the receiver operating characteristic curve [AUC] 0.970 vs. 0.890, p = 0.006), validation (AUC: 0.946 vs. 0.828, p = 0.047) and test (AUC: 0.934 vs. 0.842, p = 0.040) cohorts, respectively. Decision curve analysis of combined training, validation and test cohorts revealed that the multiparametric clinic-ultrasomics nomogram had a higher overall net benefit than the conventional clinic-radiologic model. The multiparametric clinic-ultrasomics nomogram can accurately predict the malignancy of ESTTs.


Addressing huge spatial heterogeneity induced by virus infections in lentil breeding trials.
Spatial heterogeneity can have serious effects on the precision of field experimentation in plant breeding. In the present study the capacity of the honeycomb design (HD) to sample huge spatial heterogeneity was appraised. For this purpose, four trials were conducted each comprising a lentil landrace being screened for response to viruses. Huge spatial heterogeneity was reflected by the abnormally high values for coefficient of variation (CV) of single-plant yields, ranging 123-162 %. At a given field area, increasing the number of simulated entries was followed by declined effectiveness of the method, on account of the larger circular block implying greater intra-block heterogeneity; a hyperbolic increasing pattern of the top to bottom entry mean gap (TBG) indicated that a number of more than 100 replicates (number of plants per entry) is the crucial threshold to avoid significant deterioration of the sampling degree. Nevertheless, the honeycomb model kept dealing with variation better than the randomized complete block (RCB) pattern, thanks to the circular shape and standardized type of block that ensure the less possible extra heterogeneity with expanding the area of the block. Owing to the even and systematic entry allocation, breeders do not need to be concerned with the extra spatial heterogeneity that might induce the extra surface needed to expand the size of the block when many entries are considered. Instead, they could improve accuracy of comparisons with increasing the number of replicates (circular blocks) despite the concomitant greater overall spatial heterogeneity.


Parasellar Schwannomas: Extradural vs Extra-Intradural Surgical Approach.
Schwannomas of the parasellar region may arise from the trigeminal, oculomotor, trochlear, and abducens nerves. To define the tumor origin, location, and dural relationship (extradural vs extra-intradural vs cisternal) on preoperative magnetic resonance imaging (MRI), in order to plan the best surgical approach (purely extradural vs extra-intradural). Twenty-four patients with parasellar schwannomas who underwent surgery were retrospectively analyzed. Twenty arose from the trigeminal nerve (7 intracavernous and 13 within the Meckel's cave), 3 from the oculomotor nerve, and 1 from the abducens nerve. The preoperative identification of the tumor location (extradural vs extra-intradural vs cisternal) and the nerve of origin was defined on MR sequences. All patients were operated on through a pterional approach (extradural or extra-intradural route). The tumor location was correctly defined on MRI in 22 out of 24 cases (92%) and the nerve of origin in 22 (92%). An extradural approach without intradural exploration was performed in all 5 intracavernous trigeminal schwannomas, in 11 out of 13 of the Meckel's cave, and in 2 schwannomas of the oculomotor nerve. Two schwannomas of the Meckel's cave with transgression of the medial dural wall, 1 of the oculomotor nerve, and the abducens nerve schwannoma required an extra-intradural approach. Complete tumor resection was obtained in 19 out of 24 cases (80%). The pterional extradural approach is sufficient for Dolenc type I and II trigeminal schwannomas, excepting for those transgressing the inner dural layer. Schwannomas of the oculomotor and abducens nerves with cisternal location require an extradural-intradural approach.


New Evidence for Hypnozoite-Independent Plasmodium vivax Malarial Recurrences.
Information provided in recent, related papers has wide-ranging implications concerning, inter alia, the transmission of malaria, drug treatment, and eradication of the disease. Additionally, the research results represent support for the idea that recurrences of Plasmodium vivax malaria can arise from both liver hypnozoites and extravascular merozoites in bone marrow.


Interruptions and miscommunications in surgery: an observational study.
In surgery, as much as 30% of procedure-specific information may be lost as a result of miscommunication. We assessed the relationship between interruptions, team familiarity, and miscommunications across a purposive sample of 160 surgical procedures in 10 specialties during a six-month period. Descriptive analysis was used to quantify interruptions in respect to the source (ie, conversational, procedural) and type of miscommunication (ie, audience, purpose, occasion, content, experience). Results revealed an inverse correlation between the length of time that teams had worked together and the number of miscommunications in surgery (τ = -.33, P < .01). There was a positive correlation between the number of intraoperative interruptions and the number of miscommunications (τ = .30, P < .01). These results may help to inform the development of evidence-based interventions designed to mitigate the effects of miscommunications in surgery.


Association between dietary patterns and hypertension among Han and multi-ethnic population in southwest China.
Different dietary patterns and the risks of hypertension in various diet exposures among multi-ethnic population in southwest China remain extremely scarce. The aim of this study is to identify dietary patterns and explore the association between dietary patterns and the risk of hypertension among Han and multi-ethnic population in southwest China. A representative sample of 3591 participants of Han, and multi-ethnic population were recruited by stratified cluster sampling in Diqing of Yunnan Province, southwest China from September 2012 to January 2013. Participants who were under 18 years old or who could not clearly answer the questions and those who used the anti-hypertensive medication were excluded from this survey. All participants reported their dietary intakes using validated food frequency questionnaires (FFQ), and their blood pressures were measured by standardized procedures. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. Dietary patterns were identified by factor analysis with principal component. Logistic regression was used to explore the association between dietary patterns and hypertension. The overall prevalence of hypertension was 30.5% among Han and multi-ethnic population in Diqing, Yunnan Province. Three dietary patterns were identified in this study, defined as 'Grassland healthy', 'Tuber and meat', and 'Fruit and vegetable'. Participants in the 5th quintile of the three dietary patterns were at a lower risk of hypertension compared with those in the 1st quintile. The odds ratio (OR) for the 5th quintile of 'Grassland healthy' pattern, 'Tuber and meat' and 'Fruit and vegetable' was 0.693 (95% CI: 0.537-0.893, p = 0.005), 0.678 (95% CI: 0.530-0.868, p = 0.002), 0.759 (95% CI: 0.593-0.970, p = 0.028), respectively. After further adjustment of participants' age, the negative association between the 'Grassland healthy' pattern and the prevalence of hypertension persisted (OR = 0.703, 95% CI: 0.535-0.924, p = 0.012). However, the significant associations between the other two dietary patterns and hypertension disappeared. The 'Grassland healthy' dietary pattern is associated with lower risk of hypertension, whereas there is no significant associations between the other two dietary patterns and hypertension among Han and multi-ethnic population in Diqing of Yunnan province, southwest China.


A study on lipids in the adrenal and kidney of squirrel after prostaglandin A2 treatment.
Prostaglandins have been assigned both physiological and pharmacological properties. Moreover, they have been identified in the renal tissue. Nevertheless, effects of exogenous prostaglandins on different systems are not fully known. Since PGA2 escapes destruction in the lungs, it functions as circulatory hormone. How prostaglandins of A group effect lipid metabolism in renal and adrenal tissues has been studied during this investigation. Qualitative and quantitative studies thus performed showed that PGA2 stimulated lipid activities in both the tissues. Whether they inhibited the transport of lipids away from these tissues or enhanced their biosynthesis is not known at present. However, histochemical studies on neutral lipids and phospholipids show that PGA2 stimulates lipid synthesis in these two issues.


Association of reproductive history with hypertension and prehypertension in Chinese postmenopausal women: a population-based cross-sectional study.
Hypertension and prehypertension may have important roles in the etiology of cardiovascular disease. However, the risk factors of hypertension and prehypertension have not been thoroughly elucidated to date. This study intended to explore the relative effects between reproductive history and the prevalence of hypertension and prehypertension. A population-based cross-sectional survey of postmenopausal women (n=6252), aged 41-93 years, was conducted from August 2013 to August 2015. All subjects, selected by the multistage random sampling method in Henan province, were categorized as normotension, prehypertension and hypertension according to blood pressure (BP) levels. Ordinal logistic regression models were used to estimate the risks of prehypertension and hypertension with three categories of BP as dependent variables. Hypertension was associated with a positive history of induced abortion (adjusted odds ratio (OR)=1.190, 95% confidence interval (CI): 1.020, 1.388), but there was no association between hypertension and a positive history of spontaneous abortion (adjusted OR=1.126, 95% CI: 0.973, 1.303) after adjusting for age, alcohol consumption, education status, smoking, body mass index, physical activity and occupation. Compared with women with one or no children, those with two or three children were at a lower risk of hypertension (adjusted OR=0.605, 95% CI: 0.434, 0.845). In addition, individuals with an age of menopause between 46 and 51 years may have a decreased risk of both prehypertension and hypertension, especially in terms of systolic BP. In conclusion, a positive history of induced abortion may be a predictive risk factor for hypertension and prehypertension. However, a menopausal age of 46-51 years or having two children may be protective factors against hypertension and prehypertension.


Interaction Mechanism between OVA and Flavonoids with Different Hydroxyl Groups on B-Ring and Effect on Antioxidant Activity.
Ovalbumin (OVA) is a common carrier with high efficiency to deliver flavonoids. The aim of this study was to investigate the interaction mechanism of OVA and four flavonoids (quercetin (Que), myricetin (Myri), isorhamnetin (Ish), and kaempferol (Kaem)) with similar structures by fluorescence spectra, SDS-PAGE, FT-IR, and molecular docking analysis, and the effect on the antioxidant abilities of flavonoids was also evaluated. Results indicated that the antioxidant activity of flavonoids was positively correlated to the number of phenolic hydroxyl groups of on the B-ring, and weakened when the C-3' position was replaced by a methoxy group. The addition of OVA enhanced the antioxidant activity of Que/Kaem, while it masked the antioxidant activity of Myri. The formation of Que/Myri/Ish/Kaem-OVA complexes was a spontaneous exothermic process driven mainly by hydrogen bond and van der Waals force, which could result in the change in OVA conformation and induce the transformation of α-helix to β-sheet. Among these, Kaem exhibited the strongest binding ability with OVA, and showed the greatest impact on the secondary and conformational structure of OVA, followed by Que. The hydroxylation of C-3' and methoxylation of C-5' weaken the interaction of Kaem with OVA. Molecular docking analysis suggested that Que, Myri, Ish, and Kaem formed six, three, five, and four hydrogen bonds with OVA, and the number of hydrogen bonds was not positively correlated with their binding constants. Our findings can provide a theoretical basis for the application of OVA on improving the antioxidant activity of flavonoids, and may help to explain the delivery efficiency of OVA on different bioactive constituents.


Evaluating routine diuretics after coronary surgery: a prospective randomized controlled trial.
Routine diuretic administration after cardiopulmonary bypass is common despite the lack of evidence for its benefit. We performed a prospective study to evaluate if diuretics assist in weight loss or alter clinical outcome. Seventy-nine patients undergoing primary elective coronary bypass surgery were randomized to either diuretic (fusemide and amiloride) or placebo (lactose) postoperatively until preoperative weight was achieved or for 5 days in total. Proportions were compared with chi2 or Fisher's exact test. Forty patients were randomized to diuretics and 39 to placebo. By day 5, 97% of patients (37 of 38) still in the diuretic arm, and 74% of patients (29 of 39) in the placebo arm, achieved preoperative weight (p = 0.02). There were no differences in clinical outcomes. Routine diuretics promote an earlier diuresis but no clinical benefits are apparent in low risk patients with normal renal function. Clinicians should reconsider routine diuretic prescription in this setting.


Comparison of the effect of educational and self-management interventions on adherence to treatment in hemodialysis patients: A systematic review and meta-analysis of randomized controlled trials.
Adherence to fluid intake, diet, and drug management is very important in hemodialysis patients. Educational and self-management interventions are frequently used to improve adherence to treatment in hemodialysis patients. To synthesize a comparison of the effect of educational and self-management interventions on adherence to treatment in hemodialysis patients in randomized controlled trials. Systematic searches were conducted using 11 multidisciplinary databases in June 2020. The PRISMA checklist was used. The subgroup analysis was used to compare the effect of educational and self-management interventions on adherence to fluid intake, diet, and drug management. In the included studies, educational interventions were performed ranging from 15 to 60 minutes, in 1-72 sessions. Self-management interventions were performed ranging from 10 to 120 minutes, in 1-84 sessions. The overall effect of educational interventions was small on adherence to fluid intake (P = .019, Hedges' g = -0.39), diet in serum phosphorus level (P = .001, Hedges' g = -0.35), drug management (P = .002, Hedges' g = -0.44), and not significant on adherence to diet in serum potassium level (P = .181). The overall effect of self-management interventions was small on adherence to fluid intake (P = .001, Hedges' g = -0.19) and diet in serum phosphorus level (P < .001, Hedges' g = -0.42). Additionally, the overall effect of self-management interventions was moderate on adherence to diet in serum potassium level (P = .002, Hedges' g = -0.75) and drug management (P < .001, Hedges' g = -0.55). There was no difference between the educational and self-management interventions on adherence to fluid intake, diet, and drug management (P > .05). The analysis shows that educational and self-management interventions had a beneficial effect on adherence to fluid intake, diet, and drug management and no difference between these interventions. Therefore, these interventions can be used by healthcare professionals. It is also recommended that these interventions be well defined and transferable to routine clinical practice.


Fenvalerate triggers Parkinson-like symptom during zebrafish development through initiation of autophagy and p38 MAPK/mTOR signaling pathway.
Fenvalerate (FEN), one of the most used synthetic pyrethroids, has the potential to interfere with human neural function. However, far too little attention was paid to the mechanism of FEN-induced neurotoxicity. Thus we exposed zebrafish to FEN from 4 to 120 h post fertilization (hpf), and analyzed the morphology and behavior of zebrafish. Our results showed that FEN decreased the survival rate of zebrafish, with increased malformation rates and abnormal behaviors. Furthermore, we found typical parkinson-like symptoms in FEN-exposed zebrafish with increases in parkinson's disease (PD), ubiquitin, and Lewy bodies-relevant genes. We also observed the loss of dopaminergic neurons in both FEN-exposed zebrafish and PC12 cells, which were all associated with PD-like symptoms. Besides, FEN activated autophagy by the enhanced expressions of p-mTOR, and LC3-II but the reduction of p62. Further, FEN initially activated p-p38 MAPK followed by p-mTOR, which triggered the transcription of genes responsible for autophagy process and prompted the Lewy bodies neuron generation leading to the PD-like symptoms. This process was inhibited by both 3-methyladenine (3-MA, an autophagy inhibitor) and SB203580 (a p38 MAPK selective inhibitor) in zebrafish and PC12 cells. These results suggest that FEN might cause parkinson-like symptom during zebrafish development through induction of autophagy and activation of p38 MAPK/mTOR signaling pathway. The study revealed the potential mechanism of FEN-induced neurotoxicity and should give new insights into a significant environmental risk factor of developing parkinson's disease.


Strong interlayer coupling in two-dimensional PbSe with high thermoelectric performance.
It was generally believed that weak van der Waals interactions exist between neighboring layers in the two-dimensional group-IV chalcogenides. Using PbSe as a prototypal example, we find additional strong coupling between the Pb-Pb layers, as evidenced by detailed analysis of the differential charge density plot. The coupling is covalent-like and can be fine-tuned to obviously reduce the phonon thermal conductivity but slightly change the electronic transport of PbSe layer. As a consequence, a maximumZTvalue of 2.5 can be realized at 900 K for thep-type system. Our work also offers an effective and feasible design strategy to enhance the thermoelectric performance of similar layered structures.


Models of lung transvascular fluid and protein transport.
Transport theory has been applied to lymph flow (QL), protein lymph to plasma concentration ratios (L/P), and permeability surface area for urea (PSu) in unanesthetized sheep. Three models of the plasma-interstitial barrier have been used: a single pathway fiber matrix model, a continuous cylindrical-pore model with log normal distribution of filtration coefficients, and a cylindrical two-pore model. The fiber matrix model was unable to match measured PSu, QL, and L/P. The continuous-pore model was capable of describing the data, but the fitted median pore size was inconsistent with a continuum theory. The two-pore model described steady-state data and was used in additional model applications. We explored the 90% confidence limits for the fitted structural parameters of the two-pore theory. We found that many sets of model parameters were capable of fitting the available experimental data. We therefore sought combinations of parameters that might characterize the microvascular barrier under baseline and altered permeability situations. One combination that looks promising is the ratio of large-pore to small-pore radius raised to the sixth power and multiplied by the large-pore frequency. This value remains relatively constant following elevations in microvascular pressure, saline infusions, and plasma infusions but increases dramatically after endotoxin infusion.


Integrins establish dendrite-substrate relationships that promote dendritic self-avoidance and patterning in drosophila sensory neurons.
Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations. We show that integrins control dendrite positioning on or within the epidermis in a cell autonomous manner by promoting dendritic retention on the basal surface. Loss of integrin function in neurons resulted in excessive self-crossing and dendrite maintenance defects, the former indicating a role for substrate interactions in self-avoidance. In contrast to a contact-mediated mechanism, we find that integrins prevent crossings that are noncontacting between dendrites in different three-dimensional positions, revealing a requirement for combined dendrite-dendrite and dendrite-substrate interactions in self-avoidance.


Validation and application of quantitative PCR assays using host-specific Bacteroidales genetic markers for swine fecal pollution tracking.
Genome fragment enrichment (GFE) method was applied to identify host-specific bacterial genetic markers that differ among different fecal metagenomes. To enrich for swine-specific DNA fragments, swine fecal DNA composite (n = 34) was challenged against a DNA composite consisting of cow, human, goat, sheep, chicken, duck and goose fecal DNA extracts (n = 83). Bioinformatic analyses of 384 non-redundant swine enriched metagenomic sequences indicated a preponderance of Bacteroidales-like regions predicted to encode metabolism-associated, cellular processes and information storage and processing. After challenged against fecal DNA extracted from different animal sources, four sequences from the clone libraries targeting two Bacteroidales- (genes 1-38 and 3-53), a Clostridia- (gene 2-109) as well as a Bacilli-like sequence (gene 2-95), respectively, showed high specificity to swine feces based on PCR analysis. Host-specificity and host-sensitivity analysis confirmed that oligonucleotide primers and probes capable of annealing to select Bacteroidales-like sequences (1-38 and 3-53) exhibited high specificity (>90%) in quantitative PCR assays with 71 fecal DNAs from non-target animal sources. The two assays also demonstrated broad distributions of corresponding genetic markers (>94% positive) among 72 swine feces. After evaluation with environmental water samples from different areas, swine-targeted assays based on two Bacteroidales-like GFE sequences appear to be suitable quantitative tracing tools for swine fecal pollution.


Expression and purification of lacticin Q by small ubiquitin-related modifier fusion in Escherichia coli.
Lacticin Q is a broad-spectrum class II bacteriocin with potential as an alternative to conventional antibiotics. The objective of this study was to produce recombinant lacticin Q using a small ubiquitin-related modifier (SUMO) fusion protein expression system. The 168-bp lacticin Q gene was cloned into the expression vector pET SUMO and transformed into Escherichia coli BL21(DE3). The soluble fusion protein was recovered with a Ni-NTA Sepharose column (95% purity); 130 mg protein was obtained per liter of fermentation culture. The SUMO tag was then proteolytically cleaved from the protein, which was re-applied to the column. Finally, about 32 mg lacticin Q (≥96% purity) was obtained. The recombinant protein exhibited antimicrobial properties similar to that of the native protein, demonstrating that lacticin Q had been successfully expressed by the SUMO fusion system.


Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose.
The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging.


An ELISA to detect monoclonal antibodies specific for lipid determinants of Mycoplasma pneumoniae.
An enzyme-linked immunosorbent assay (ELISA) was developed for analysis of monoclonal antibodies directed towards lipid determinants of Mycoplasma pneumoniae. Chloroform-methanol lipid extracts as well as chromatographed lipid fractions of M. pneumoniae were bound to polyvinylchloride microtiter wells. Of 293 clones positive to M. pneumoniae as detected by a whole cell ELISA, a total of 78 clones produced antibodies which selectively bound to lipid extracts of M. pneumoniae. The simplicity and reproducibility of the assay permit rapid screening for detection of antibodies directed against non-protein cellular antigens.


Extracranial anticoagulant related bleedings admitted to intensive care units: a French multicenter retrospective study.
Anticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding. A retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included. 486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2. Anticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs.


Effects of lactic acid bacteria on the uptake and distribution of the food mutagen Trp-P-2 in mice.
Lactic acid bacteria have been reported to have antimutagenic and anticarcinogenic properties in vivo and in vitro. Lactobacillus acidophilus and Bifidobacterium longum have earlier been shown to bind the food mutagen Trp-P-2 in vitro. The influence of oral supplementation with L. acidophilus NCFB 1748 and B. longum BB 536 on the uptake and distribution of 14C-labelled Trp-P-2 in several mouse tissues was quantified by liquid scintillation measurements and examined by tape section autoradiography (gives an unbiased qualitative registration of differences in overall tissue distribution) in the present investigation. Furthermore, the effect of 13-naphthoflavone (BNF), a cytochrome P4501A (CYP1A)-inducing agent, on the distribution of 14C-labelled Trp-P-2 was examined. After oral (6 mg/kg; 5 microCi) or iv (1.2 mg/kg; 1 microCi) administration of 14C-labelled Trp-P-2, high levels of radioactivity were observed in the bile, urine and contents of the gastrointestinal tract. Lower levels were present in the liver, lung, kidney, intestines, brown fat, submaxillary salivary gland and thymus. In mice supplemented with lactic acid bacteria there was a significantly decreased level (29%-73%) of radioactivity in the lung, thymus, liver, kidney, submaxillary salivary gland and small intestine as compared with controls. In mice pretreated with BNF, a low but distinct localization of radioactivity in the lung was observed, whereas no similar localization occurred in controls. The results suggest that (i) there is a decreased bioavailability of the Trp-P-2 in the majority of the tissues examined in bacteria supplemented mice and (ii) there is a low but distinct CYP1A-dependent activation of Trp-P-2 in the lung of BNF-treated mice.


Diagnostic accuracy of hepatic venous pressure gradient measurement in the prediction of stage 1 compensated liver cirrhosis in patients with chronic hepatitis B.
Hepatic venous pressure gradient (HVPG) of 6-10 mmHg has been accepted as a hemodynamic parameter of stage 1 compensated liver cirrhosis (LC). The diagnostic accuracy of HVPG in the prediction of stage 1 compensated LC has been investigated in patients with chronic hepatitis B (CHB). A total of 219 patients with CHB who underwent HVPG and liver biopsy were enrolled. The diagnostic accuracy of two methods was compared. Risk factors associated with the diagnosis of stage 1 compensated LC on the basis of the findings of HVPG, biopsy, and both HVPG and biopsy were evaluated. The HVPG score was correlated positively with the stage of biopsy (r=0.439). The sensitivity/specificity of HVPG for predicting stage 1 compensated LC were 78/81% in 6 mmHg, respectively. A total of 57 (26%), 28 (13%), and 20 (9%) patients were diagnosed with stage 1 compensated LC on the basis of the findings of HVPG, biopsy, and both HVPG and biopsy (P>0.05), respectively. Platelet/age (-0.77-0.01×platelet+0.03×age), albumin/platelet (5.05-1.19×albumin-0.01×platelet), and platelet (0.24-0.01×platelet) were found to be risk factors (logit model) for the diagnosis of stage 1 compensated LC on the basis of the findings of HVPG, biopsy, and both HVPG and biopsy. HVPG showed a positive correlation with biopsy, and platelet was found to be a common risk factor for the diagnosis of stage 1 compensated LC in patients with CHB.


Does coronary stenting following balloon angioplasty improve myocardial fractional flow reserve?
Suboptimal distal coronary flow reserve after successful balloon angioplasty has been attributed to angiographically unrecognized inadequate lumen expansion, and adjunct coronary stenting has been shown to improve coronary flow reserve. The aim of this study was to investigate whether myocardial fractional flow reserve (FFRmyo) would increase further after coronary stenting compared with balloon angioplasty alone in the same patient group. FFRmyo and quantitative coronary angiography were obtained before and after pre-stent balloon dilation, and again after stent placement in 11 patients (7 left anterior descending artery, 3 right coronary artery and 1 left circumflex artery). FFRmyo was calculated as the ratio of Pd/Pa during intracoronary adenosine 5'-triphosphate (50 micrograms and 20 micrograms in the left and right coronary arteries, respectively)-induced maximum hyperemia, where Pd represents mean distal coronary pressure measured by a 2.1 Fr infusion catheter and Pa represents mean aortic pressure measured by the guiding catheter. Percent diameter stenosis significantly decreased after balloon angioplasty (74% +/- 15% vs 37% +/- 17%, p < 0.001), and decreased further after stent placement (18% +/- 10%, p < 0.001 vs baseline and balloon angioplasty). FFRmyo after coronary stenting (0.85 +/- 0.09) was significantly higher than that at baseline (0.51 +/- 0.16, p < 0.001) and after balloon angioplasty (0.77 +/- 0.11, p < 0.05). There was a significant correlation between angiographic variables and FFRmyo. The increase in lumen dimensions after coronary stenting was followed by a further significant improvement of FFRmyo. These results suggest that coronary stenting may provide a more favorable functional status and lumen geometry of residual coronary stenosis compared with balloon angioplasty alone.


Frequency stabilization in nonlinear micromechanical oscillators.
Mechanical oscillators are present in almost every electronic device. They mainly consist of a resonating element providing an oscillating output with a specific frequency. Their ability to maintain a determined frequency in a specified period of time is the most important parameter limiting their implementation. Historically, quartz crystals have almost exclusively been used as the resonating element, but micromechanical resonators are increasingly being considered to replace them. These resonators are easier to miniaturize and allow for monolithic integration with electronics. However, as their dimensions shrink to the microscale, most mechanical resonators exhibit nonlinearities that considerably degrade the frequency stability of the oscillator. Here we demonstrate that, by coupling two different vibrational modes through an internal resonance, it is possible to stabilize the oscillation frequency of nonlinear self-sustaining micromechanical resonators. Our findings provide a new strategy for engineering low-frequency noise oscillators capitalizing on the intrinsic nonlinear phenomena of micromechanical resonators.


Exosomal miR-127-5p from BMSCs alleviated sepsis-related acute lung injury by inhibiting neutrophil extracellular trap formation.
Neutrophil extracellular traps (NETs) play an important role in sepsis-related acute lung injury (ALI). Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miRNA are becoming promising agents for the treatment of ALI. The current study aimed to elucidate the mechanism by BMSCs-derived exosomes carrying miR-127-5p inhibiting to the formation of NETs in sepsis-related ALI. We successfully isolated exosomes from BMSCs and confirmed that miR-127-5p was enriched in the exosomes. ALI mice treated with BMSCs-derived exosomes histologically improved, and the release of NETs and inflammatory factors in lung tissue and peripheral blood of mice also decreased compared with LPS group, while the protective effect of exosomes was attenuated after the knockdown of miR-127-5p. Using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, we identified CD64 as a direct target of miR-127-5p. Meanwhile, BMSCs-derived exosomes can synergize with anti-CD64 mab in ALI mice to reduce tissue damage, inhibit the release of inflammatory factors and NETs formation. The synergistic effect of exosomes was attenuated when miR-127-5p was down-regulated. These findings suggest that exosomal miR-127-5p derived from BMSCs is a potential therapeutic agent for treatment of sepsis-induced ALI through reducing NETs formation by targeting CD64.


Depressive symptomatology among Latina breast cancer survivors.
Healthcare professionals are providing care for a growing number of Latinas who are breast cancer survivors (BCS) and at greater risk for distress. This study reports on the prevalence of depressive symptomatology among a cohort of Latina BCS. This study reports the outcomes of a population-based sample of 232 Latina BCS recruited via case ascertainment from the California-Cancer and hospital registries. Fifty-three percent had elevated depressive symptoms. In the regression model, education, physical functioning, social support, family stress, functional stress, social functioning, and Spanish language preference were significantly associated with depressive symptoms. Among Latina BCS, the prevalence of depressed mood may be higher than European-Americans and presents a formidable clinical challenge. These findings underscore the need for timely, appropriate assessment of distress and its contributing factors including patients' socio-ecological contexts and family strain to inform effective patient-centered and family-centered psychosocial referrals and intervention strategies to reduce distress and the undue burden of cancer among Latinos. Latino survivors constitute an increasing proportion of patients in community medical practices. Thus, the requisite to perform follow-up cancer care that addresses the needs of the whole person is rapidly emerging in prominence as a component of medical practice. Therefore, primary care providers and oncology and mental health specialists must work collaboratively via the sharing of electronic medical records, survivorship care plans, and consultations to implement the Institute of Medicine and National Comprehensive Cancer Network recommendations by attending to the psychological status of cancer patients to optimize patient outcomes.


Gene transfer into guinea pig cochlea using adeno-associated virus vectors.
Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects. Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of the cochlea basal turn, an approach that could be used in cochlear implant surgery. At 7 days after injection, distribution of gene expression, hearing and morphology were evaluated. Adenoviral vector was also used to compare distributions of gene expression. Moreover, distribution of cell surface receptors of AAV in the cochlea was examined using immunohistochemistry. Using the perilymphatic approach, adenovirus could be transferred to mesothelial cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly efficient transfer to sensory cells. This tissue tropism of AAV could not be explained by the distribution of AAV receptors. Hearing and morphology were largely unaffected. Our results indicate that AAV vector can be safely applied to the inner ear and AAV-2/2 offers a good tool for transferring transgenes into sensory cells of the inner ear efficiently without toxicity.


Quantitative Live-Cell Ca2+ Imaging During Isotropic Cell Stretch.
Cell viability of many cell types strongly relies on their ability to adjust to mechanical conditions and alterations. Cellular mechanisms for sensing and responding to mechanical forces and pathophysiological variations in these processes have become an emerging research field in recent years. An important signaling molecule involved in mechanotransduction as in many cellular processes is Ca2+. New experimental methods to probe cellular Ca2+ signaling live under conditions of mechanical stimulation facilitate new insights into previously overlooked aspects of mechanical regulation of cells.Here, we describe a protocol for using Ca2+ imaging in combination with a cell stretching device, the IsoStretcher. Cells grown on elastic membranes can be isotopically stretched in-plane, and their intracellular Ca2+ level can be accessed online on the single cell level using fluorescent calcium indicator dyes. We show a protocol for functional screening of mechanosensitive ion channels and related drug screenings using BJ cells, a foreskin fibroblast cell line that strongly reacts to acute mechanical stimulation.


Acceptability of pandemic A(H1N1) influenza vaccination by Essential Community Workers in 2010 Alicante (Spain), perceived seriousness and sources of information.
Describe acceptability of pandemic A(H1N1) influenza vaccination by Essential Community Workers (ECWs) from Alicante province (Spain) in January 2010. Evaluate the correlation with attitudes, beliefs, professional advice and information broadcasted by media. In this cross-sectional study, face-to-face interviews were conducted with 742 ECWs to assess their attitudes towards vaccination against the pandemic influenza strain. A multivariable regression model was made to adjust the Odds Ratios (ORs). Some ECWs reported having been vaccinated with seasonal vaccine, 21.5% (95%IC 18.6-24.9); only 15.4% (95%IC 12.8-18.4) with the pandemic one. ECWs vaccinated regularly against seasonal flu (OR 5.1; 95%IC 2.9-9.1), those who considered pandemic influenza as a severe or more serious disease than seasonal flu (OR 3.8; 95%IC 2.1-6.7) and those who never had doubts about vaccine safety (OR 3.7; 95%IC2.1-6.7) had a better acceptance of pandemic vaccine. Finally, 78.7% (95%IC 75.1-81.4) had doubts about pandemic vaccine's effectiveness. The vast amount of information provided by the media did not seem to be decisive to prevent doubts or to improve the acceptability of the vaccine in ECWs. Professional advice should be the focus of interest in future influenza vaccination campaigns. These results should be taken into account by health authorities.


Deep learning based hybrid prediction model for predicting the spread of COVID-19 in the world's most populous countries.
COVID-19 has a disease and health phenomenon and has sociological and economic adverse effects. Accurate prediction of the spread of the epidemic will help in the planning of health management and the development of economic and sociological action plans. In the literature, there are many studies to analyse and predict the spread of COVID-19 in cities and countries. However, there is no study to predict and analyse the cross-country spread in the world's most populous countries. In this study, it was aimed to predict the spread of the COVID-19 epidemic. The motivation of this study is to reduce the workload of health workers, take preventive measures and optimize health processes by predicting the spread of the COVID-19 epidemic. A hybrid deep learning model was developed to predict and analyse COVID-19 cross-country spread and a case study was carried out for the world's most populous countries. The developed model was tested extensively using RMSE, MAE and R2. The experimental results showed that the developed model was more successful in predicting and analysis of COVID-19 cross-country spread in the world's most populous countries than LR, RF, SVM, MLP, CNN, GRU, LSTM and base CNN-GRU. In the developed model, CNN performs convolution and pooling operations to extract spatial features from the input data. GRU provides learning of long-term and non-linear relationships inferred by CNN. The developed hybrid model was more successful than the other models compared, as it enabled the effective features of the CNN and GRU models to be used together. The prediction and analysis of the cross-country spread of COVID-19 in the world's most populated countries can be presented as a novelty of this study.


Mechanism of substrate recognition and PLP-induced conformational changes in LL-diaminopimelate aminotransferase from Arabidopsis thaliana.
LL-Diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal phosphate (PLP)-dependent enzyme in the lysine biosynthetic pathways of plants and Chlamydia, is a potential target for the development of herbicides or antibiotics. This homodimeric enzyme converts L-tetrahydrodipicolinic acid (THDP) directly to LL-DAP using L-glutamate as the source of the amino group. Earlier, we described the 3D structures of native and malate-bound LL-DAP-AT from Arabidopsis thaliana (AtDAP-AT). Seven additional crystal structures of AtDAP-AT and its variants are reported here as part of an investigation into the mechanism of substrate recognition and catalysis. Two structures are of AtDAP-AT with reduced external aldimine analogues: N-(5'-phosphopyridoxyl)-L-glutamate (PLP-Glu) and N-(5'-phosphopyridoxyl)- LL-Diaminopimelate (PLP-DAP) bound in the active site. Surprisingly, they reveal that both L-glutamate and LL-DAP are recognized in a very similar fashion by the same sets of amino acid residues; both molecules adopt twisted V-shaped conformations. With both substrates, the alpha-carboxylates are bound in a salt bridge with Arg404, whereas the distal carboxylates are recognized via hydrogen bonds to the well-conserved side chains of Tyr37, Tyr125 and Lys129. The distal C(epsilon) amino group of LL-DAP is specifically recognized by several non-covalent interactions with residues from the other subunit (Asn309*, Tyr94*, Gly95*, and Glu97* (Amino acid designators followed by an asterisk (*) indicate that the residues originate in the other subunit of the dimer)) and by three bound water molecules. Two catalytically inactive variants of AtDAP-AT were created via site-directed mutagenesis of the active site lysine (K270N and K270Q). The structures of these variants permitted the observation of the unreduced external aldimines of PLP with L-glutamate and with LL-DAP in the active site, and revealed differences in the torsion angle about the PLP-substrate bond. Lastly, an apo-AtDAP-AT structure missing PLP revealed details of conformational changes induced by PLP binding and substrate entry into the active site.


Laparoscopy in the surgical treatment of rectal cancer in Germany 2000-2009.
The goal of this registry study was to compare open surgery with planned laparoscopy and then with laparoscopic to open conversion for rectal cancer surgery. The study included 17,964 rectal cancer patients, operated on between 1 January 2000 and 31 December 2009, from 345 hospitals in Germany. All statistical tests were two-sided, with the χ(2) test (Pearson correlation) for patients and tumour characteristics. Fisher's exact test was used for complications and 30-day mortality. Of the 17,964 rectal cancer patients, 16,308 (90.8%) had an open procedure and 1656 (9.2%) were started with a laparoscopy. The 1455 patients with completed laparoscopic operations had fewer intra-operative and postoperative complications (5.4%vs 7.0%, P = 0.020, and 20.5%vs 25.8%, P < 0.001, respectively) and a lower 30-day mortality rate (1.1%vs 1.9%, P = 0.023). Of the 1656 planned laparoscopies, 201 (12.1%) were converted to open. The converted group suffered more intra-operative complications (18.9%vs 3.6% for completed laparoscopy and 7.0% for open surgery, P < 0.0001) and postoperative complications (32.3%vs 18.9% for completed laparoscopy and 25.8% for open operations, P < 0.0001). The converted group also had a higher 30-day mortality rate (2.0%vs 1.0% for completed laparoscopy and 1.9% for open surgery, P = 0.043). The more favourable patient profile provided justification for a laparoscopic procedure. For those converted to an open procedure, however, there were significantly more complications than planned open surgery patients. A move away from the standard open procedure for rectal cancer surgery and towards laparoscopy is not yet feasible.


[Ambulatory blood sugar control of diabetics on insulin therapy during pregnancy by means of the Eyetone reflectometer].
The data obtained in this study show that sufficiently accurate blood glucose values can be obtained by the pregnant diabetic with the Eyetone reflectometer. It is possible to lower the blood glucose value of the pregnant diabetic to the normal range as soon as pregnancy is confirmed. Prolonged hospital confinement can be avoided by using this outpatient blood glucose measurement procedure.


Relationship between Plaque Echo, Thickness and Neovascularization Assessed by Quantitative and Semi-quantitative Contrast-Enhanced Ultrasonography in Different Stenosis Groups.
The aim of this study was to determine the relationship between plaque echo, thickness and neovascularization in different stenosis groups using quantitative and semi-quantitative contrast-enhanced ultrasound (CEUS) in patients with carotid atherosclerosis plaque. A total of 224 plaques were divided into mild stenosis (<50%; 135 plaques, 60.27%), moderate stenosis (50%-69%; 39 plaques, 17.41%) and severe stenosis (70%-99%; 50 plaques, 22.32%) groups. Quantitative and semi-quantitative methods were used to assess plaque neovascularization and determine the relationship between plaque echo, thickness and neovascularization. Correlation analysis revealed no relationship of neovascularization with plaque echo in the groups using either quantitative or semi-quantitative methods. Furthermore, there was no correlation of neovascularization with plaque thickness using the semi-quantitative method. The ratio of areas under the curve (RAUC) was negatively correlated with plaque thickness (r = -0.317, p = 0.001) in the mild stenosis group. With the quartile method, plaque thickness of the mild stenosis group was divided into four groups, with significant differences between the 1.5-2.2 mm and ≥3.5 mm groups (p = 0.002), 2.3-2.8 mm and ≥3.5 mm groups (p <0.001) and 2.9-3.4 mm and ≥3.5 mm groups (p <0.001). Both semi-quantitative and quantitative CEUS methods characterizing neovascularization of plaque are equivalent with respect to assessing relationships between neovascularization, echogenicity and thickness. However, the quantitative method could fail for plaque <3.5 mm because of motion artifacts.


The Role of Consultation Clinics in Services for Children and Young People with Learning Disabilities and/or Autism.
Consultation and supervision are familiar to many professionals, and their relevance to those working with children with learning disabilities and autism is discussed. Consultation Clinics for Community Learning Disability Nurses and others were set up by a specialist Child and Adolescent Mental Health team servicing an area with a general population of 750,000. They were provided by a clinical psychologist and a psychiatrist, and data on their use were collected over a 16 month period. There were differences in frequency of use between nurses based in more rural teams and those in city teams. The number of children discussed increased over time, and approximately half continued to be supported by the discussant, rather than being referred to the Tier 3 service. Suggestions are made as to the possible impact and benefits, with discussion also considering the role of professional responsibilities in consultative services.


Identification of cases with adverse neonatal outcome monitored by cardiotocography versus ST analysis: secondary analysis of a randomized trial.
To evaluate whether correct adherence to clinical guidelines might have led to prevention of cases with adverse neonatal outcome. Secondary analysis of cases with adverse outcome in a multicenter randomized clinical trial. Nine Dutch hospitals. Pregnant women with a term singleton fetus in cephalic position. Data were obtained from a randomized trial that compared monitoring by STAN® (index group) with cardiotocography (control group). In both trial arms, three observers independently assessed the fetal surveillance results in all cases with adverse neonatal outcome, to determine whether an indication for intervention was present, based on current clinical guidelines. Adverse neonatal outcome cases fulfilled one or more of the following criteria: (i) metabolic acidosis in umbilical cord artery (pH < 7.05 and base deficit in extracellular fluid >12 mmol/L); (ii) umbilical cord artery pH < 7.00; (iii) perinatal death; and/or (iv) signs of moderate or severe hypoxic ischemic encephalopathy. We studied 5681 women, of whom 61 (1.1%) had an adverse outcome (26 index; 35 control). In these women, the number of performed operative deliveries for fetal distress was 18 (69.2%) and 16 (45.7%), respectively. Reassessment of all 61 cases showed that there was a fetal indication to intervene in 23 (88.5%) and 19 (57.6%) cases, respectively. In 13 (50.0%) vs. 11 (33.3%) cases, respectively, this indication occurred more than 20 min before the time of delivery, meaning that these adverse outcomes could possibly have been prevented. In our trial, more strict adherence to clinical guidelines could have led to additional identification and prevention of adverse outcome.