[Arbovirus eco-epidemiology in the area affected by the Cuiabá-Santarém Highway (BR-163), Pará State, Brazil].
The current study describes the eco-epidemiological aspects of arbovirus diseases in the municipalities (counties) of Novo Progresso and Trairão, Para State, Brazil, in the area affected by highway BR-163. Hemagglutination inhibition (HI) antibodies to different arboviruses were detected, with monotypic reactions to MAYV and OROV, two important arboviruses associated with epidemics in the Amazon. IgM antibodies to OROV and MAYV were found in human sera, suggesting recent infections by these viruses. Two DENV-3 strains were isolated from febrile patients in Novo Progresso and identified as genotype III strains. In general, the data suggest that the area displays ideal conditions for maintenance and circulation of arboviruses, plus a population with low immunization levels. Dynamic surveillance of local immigrants and wild animals is thus important, focusing on antibody prevalence and isolation of arboviruses, thereby allowing effective control of infections by these viral agents in the resident population along highway BR-163 in Pará State.


Effect of carvedilol on neuronal survival and poly(ADP-ribose) polymerase activity in hippocampus after transient forebrain ischemia.
Carvedilol a beta-adrenoreceptor antagonist with potent antioxidant properties raises high expectations in therapy of ischemia. In this study the effect of carvedilol on neuronal survival after transient forebrain ischemia in gerbils was investigated. The role of poly(ADP-ribose) polymerase (PARP-1) in this process was evaluated. Our data indicated that carvedilol administered subcutaneously in a dose of 7 or 70 mg/kg b.w. directly after 5 min of transient forebrain ischemia protects significant population of neurons in hippocampal area CA1, but has no effect after induction of prolonged 10 min ischemia. Carvedilol significantly decreased PARP activity in hippocampus that was markedly increased after both 15 min and 4 days of reperfusion following 5 min of ischemia. Moreover, carvedilol prevented NAD+ depletion after ischemic-reperfusion insult. These results indicated that carvedilol protects neurons against death and suggested that suppression of PARP activity during reperfusion could be involved in this process.


A real-time in vitro assay to evaluate the release of macromolecules from liposomes.
The availability of a real-time assay to experimentally investigate the release of encapsulated proteins would be beneficial given the interest in the use of liposomes as a drug delivery vehicle. Although simple assays for small molecular weight substances exist, assays to evaluate macromolecules do not. Here we describe a method that detects the release of model macromolecules from liposomes in real time. The assay employs the intermolecular distance-dependent phenomenon of fluorescence resonance energy transfer (FRET) between the fluorophore donor, fluorescein (FITC), and fluorescent quencher, QSY® 9. The macromolecular species were conjugated to the markers fluorescein (44kDa dextran) and QSY® 9 (67 kDa bovine serum albumin, BSA). Following confirmation of quenching between FITC-Dex and QSY® 9-BSA, liposomes were loaded with the macromolecular markers and subjected to various treatments (high-pressure extrusion and Triton X solubilisation) to cause release from liposomes. An increase in FITC fluorescence was observed when liposomes were subjected to extrusion cycles. Surprisingly, the addition of Triton X did not cause an increase in fluorescence probably because the FRET pair became associated with mixed micelles. This assay method should be useful in studies to investigate the mechanisms by which macromolecules are released from liposomes, particularly when liposomes are exposed to release-triggers (eg, temperature change, pH change, ultrasound). Such understanding will underpin the formulation of triggered liposomal delivery systems for macromolecules.


NMR-guided molecular docking of a protein-peptide complex based on ant colony optimization.
Standard docking approaches used for the prediction of protein-ligand complexes in the drug development process have problems identifying the correct binding mode of large flexible ligands. Herein we show how additional experimental data from NMR experiments can be used to predict the binding mode of a mucin 1 (MUC-1) pentapeptide recognized by the breast-cancer-selective monoclonal antibody SM3. Distance constraints derived from trNOE and saturation transfer difference NMR experiments are combined with the docking approach PLANTS. The resulting complex structures show excellent agreement with the NMR data and with a published X-ray crystal structure. The method was then further tested on two complexes in order to demonstrate its more general applicability: T-antigen disaccharide bound to Maclura pomifera agglutinin, and the inhibitor SBi279 bound to S100B protein. Our new approach has the advantages of being fully automatic, rapid, and unbiased; moreover, it is based on relatively easily obtainable experimental data and can greatly increase the reliability of the generated structures.


[A comparison of two modalities of complex chemoradiotherapy for locally advanced nasopharyngeal carcinoma].
Two modalities of complex chemoradiotherapy for locally advanced nasopharyngeal carcinoma stage III-IV were compared in the treatment of 52 patients. Thirty-four patients (group I) received polychemotherapy: cisplatin--100 mg/sq.m, i.v., dropwise, on day 4, plus ACOP (adriamycin 35 mg/sq.m, i.v.--4; cyclophosphamide 750 mg/sq.m, i.v.--4, day 1; vincristine 1.4 mg/sq.m, i.v.--4, and prednisolone 100 mg/sq.m, per os, days 1-5; group II (18)--cisplatin 100 mg/sq.m, day 4, plus 5-FU 1,000 mg, i.v.--4, injection, days 1-3. Full response was registered in 93.7% (group I) and 93.3% (group II). Overall 5-year and relapse-free survival was 85 and 63% (group I), and 83 and 56% (group II), respectively. There were no significant differences in radiation-related injury incidence in both groups. The best results were reported with chemoradiotherapy using two courses: an induction one and an adjuvant cisplatin drugs treatment concurrent with ACOP or 5-FU.


Concentrations of fecal bacteria and nutrients in soil surrounding round-bale feeding sites.
An experiment was conducted over 7 mo (January to July 2003) to evaluate fecal bacteria and nutrient concentrations in soil surrounding round-bale feeders at 10 winter feeding sites. Soil samples 15 cm in depth were taken monthly from each site at distances of 3, 12, 21, and 30 m from the feeder. Soil samples were taken before livestock access to the sites (January), during the feeding period (February, March, and April), and after cattle removal from the sites (May, June, and July). Results indicated that fecal bacteria concentrations increased over the feeding period and were greatest at close proximity to round-bale feeders. Fecal Escherichia coli concentrations were greater in April (P < 0.03) at 3 and 12 m than in all other months, except March. At 21 and 30 m from the feeders, fecal E. coli concentrations were greater in April (P < 0.01) than in other months. At 3 m from the feeder, fecal Streptococci concentrations were greater in March and April (P < 0.01) than in other months. Although fecal E. coli concentrations in July had returned to levels similar to those in the prefeeding period, fecal Streptococci remained at higher concentrations (P < 0.05) than at the prefeeding period. The concentration of soil P at 3 m was greater in April (P < 0.02) than in January, February, and May. After cattle access to the sites, soil DM content was consistently less for samples taken at 3 m from the feeder compared with the other distances, with quadratic decreases (P < 0.02) noted in March, April, and July, and linear decreases (P < 0.01) in May and June, as distance from the feeder decreased.


Ultrathin platinum nanowires grown on single-layered nickel hydroxide with high hydrogen evolution activity.
Design and synthesis of effective electrocatalysts for hydrogen evolution reaction in alkaline environments is critical to reduce energy losses in alkaline water electrolysis. Here we report a hybrid nanomaterial comprising of one-dimensional ultrathin platinum nanowires grown on two-dimensional single-layered nickel hydroxide. Judicious surface chemistry to generate the fully exfoliated nickel hydroxide single layers is explored to be the key for controllable growth of ultrathin platinum nanowires with diameters of about 1.8 nm. Impressively, this hybrid nanomaterial exhibits superior electrocatalytic activity for hydrogen evolution reaction in alkaline solution, which outperforms currently reported catalysts, and the obviously improved catalytic stability. We believe that this work may lead towards the development of single-layered metal hydroxide-based hybrid materials for applications in catalysis and energy conversion.


Genetic instability in the mating type system of Tetrahymena pigmentosa.
Selfing clones of Tetrahymena pigmentosa show several interesting genetic features, and provide some insight into the mechanisms of mating type (mt) determination. They differ significantly from those of Tetrahymena thermophila. They are distributed nonrandomly in crosses. Their rates of stabilization are highly variable, but most are much lower than those reported for T. thermophila. A number of subclones derived from nearly all the selfers have maintained stable mts in culture for several years. However, some subclones manifest persistent selfing, long after the calculated completion of allelic assortment for heterozygous loci. This phenomenon along with the perpetual maintenance of dominant mts in heterozygotes shows that phenotypic assortment is not involved in mt expression. In crosses, many selfers exhibit quantitative and qualitative aberrations in the transmission of alleles to the gametes; some of the micronuclear changes underlying these aberrations occur during vegetative growth. There are rare illegitimate appearances of dominant alleles in sexual progeny, and more common illegitimate appearances of the most recessive phenotype.--Various models to explain mt determination in this species are considered. One which might account for the troubling phenomena of the system consists of an active mat expression site, with "cassettes" at other sites specific for the different dominant alleles and capable of transposition to the expression site.


A Geodemographic Service Coverage Analysis of Travel Time to Glaucoma Specialists in Florida.
Approximately 1 in 9 Florida residents over the age of 65 years (438,642 people) live more than an hour away from a glaucoma specialist, which represents a significant barrier to care. To describe access to glaucoma care for Florida's elderly population using travel time to American Glaucoma Society (AGS) member offices. For this cross-sectional service coverage analysis, a list of AGS member locations was extracted from the AGS website, and addresses were geocoded using ArcGIS Online. Driving time regions were created using the service area tool in ArcGIS Pro 2.4 and overlaid with 2010 United States Census and 2016 American Community Survey data for all Florida residents age 65 or older. Fifty-eight AGS member providers with 65 locations were identified and geocoded. There were 3,797,625 individuals aged over 65 years in Florida, of which 1,153,320 (30.4%) lived within 15 minutes of driving time from an AGS provider's office, 2,586,825 (68.1%) within 30 minutes, 3,358,983 (88.4%) within 60 minutes, and 3,491,815 (91.9%) within 120 minutes. The areas with the lowest access include rural areas near Lake Okeechobee and the Florida Panhandle. The population living beyond a 60-minute drive was more likely to be White, non-Hispanic and older, but less likely to be living below the federal poverty level or receiving public assistance than the population living within a 60-minute drive. There is a significant travel burden for the elderly community of Florida to reach AGS providers. Additional studies could help identify other social barriers to accessing glaucoma providers in Florida and beyond in an effort to improve patient compliance and, ultimately, vision outcomes.


Physiology of diving in marine mammals.
Natural dives are usually short and aerobic, involving swimming effort that is not energetically costly. Present evidence indicates few, if any, major biochemical enzyme adaptations that would promote an extended anaerobic capacity in marine mammals. We have discussed the lack of evidence for unusual biochemical adaptations for anaerobiosis and the importance and characteristics of natural aerobic dives. What explanation can we offer for the known capability of some marine mammals, such as Weddell seals and sperm whales, to remain submerged for over an hour? Attributes that serve them well for shorter dives are important also for long dives, such as: (a) a large total oxygen store relative to body size, and (b) parsimonious use of blood oxygen due to the lowered energy requirements of various organs. During long dives, some organs deplete their oxygen stores, become predominately dependent on anaerobic metabolism, and build up large quantities of lactate. The result is a degree of fatigue that leaves the animal incapable of further intense diving activities for some time. Consequently, long anaerobic dives are quite rare in nature.


Kinetic study of the fast thermal cis-to-trans isomerisation of para-, ortho- and polyhydroxyazobenzenes.
The thermal cis-to-trans isomerisation process has been studied for a series of para-, ortho- and polyhydroxy-substituted azobenzenes in different solvents. The kinetics of the thermal back reaction for the p-hydroxy-substituted azobenzenes depend strongly on the nature of the solvent used, with relaxation times ranging from 200-300 milliseconds in ethanol to half an hour in toluene. Otherwise, the process rate is mainly independent of the solvent nature for the ortho substituted analogues. Polyhydroxy-substituted azobenzenes show very much faster kinetics than the para- and ortho- monohydroxyazoderivatives. With relaxation times of 6-12 milliseconds in ethanol, they are optimal molecules for designing fast optical switching devices. All the hydroxyazoderivatives thermally isomerise from the metastable cis form to the thermodynamically stable trans isomer through a rotational mechanism.


Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study.
To evaluate the cardiac safety of central nervous system stimulants in children and adolescents. Population based retrospective cohort study. Automated healthcare claims data from 1,219,847 children and young people eligible for 28 state Medicaid programmes from 1999 to 2006 linked to the Social Security Death Master File and the National Death Index. Children and young people age 3-18 entered the cohort at the first diagnosis of a mental health condition commonly treated with stimulants (such as attention-deficit/hyperactivity disorder) after a minimum period of six months' eligibility and were followed until loss of eligibility, their 19th birthday, admission to hospital for longer than 30 days, or death. Exclusion criteria included transplant recipients, receipt of dialysis, or claims indicating substance misuse. We retained high risk groups with similar use of stimulants as low risk children (such as children with congenital heart disease). Sociodemographic characteristics, cardiac risk factors, and psychiatric diagnoses obtained from before the index period were summarised with a propensity score. We used discrete survival analysis to estimate the relative risk for periods of stimulant use and non-use, adjusted for propensity score and antipsychotic use for the full cohort and the high risk and low risk groups. Composite endpoint of stroke, acute myocardial infarction, or sudden cardiac death; a secondary composite endpoint added ventricular arrhythmia A total of 66 (95 including ventricular arrhythmia) events occurred during 2,321,311 years of follow-up. The odds ratio adjusted for propensity score and antipsychotic use for current versus no stimulant use was 0.62 (95% confidence interval 0.27 to 1.44), with a corresponding adjusted incidence rate of 2.2 and 3.5 per 100,000 patient years for current stimulant and non-use, respectively. Twenty six events occurred in high risk patients (incidence rate 63 per 100,000 patient years) with an odds ratio of 1.02 (0.28 to 3.69). Odds ratios for the secondary endpoint were similar to those for the primary endpoint (0.74, 0.38 to 1.46). Treatment of children with central nervous stimulants is not significantly associated with an increase in the short term risk of severe cardiac events. Analyses cannot be generalised to children with long term use of stimulants. Furthermore, long term effects of slight increases in heart rate or blood pressure are unknown.


Palliative care organization and staffing models in residential hospices: Which makes the difference?
The number of patients using palliative care services, particularly residential hospices, is increasing. Policymakers are urging these services to reflect on the most effective organizational strategies for meeting patients' complex care needs. To analyze the predictive power of staffing, structure and process indicators towards optimal control of patients' clinically significant symptoms over time. Secondary analysis of data from a multicentre prospective longitudinal observational study (PRELUdiHO) collected between November 2017 and September 2018. Adult patients (n = 992) enrolled in 13 Italian residential hospices. Two generalized estimating equations logistic models were built, both with number of hospice beds and length of stay as independent variables as well as, in one case, patient-to-healthcare worker ratios, and, in the other, health professionals' qualification levels. Dependent variables were six not clinically significant (score<4) symptoms: pain, nausea, shortness of breath, feeling sad, feeling nervous, and 'how you feel overall', according to the Edmonton Symptom Assessment System revised (ESAS-r) scale. The generalized estimating equations indicators on staff revealed the following 'optimal' model: Patient-to-Physician ratio (5.5:1-6.5:1); Patient-to-Nurse ratio (1.5:1-2.7:1); Patient-to-Nurse-Assistant ratio (4.1:1-6.3:1); with the most balanced staff composition including 19% physicians, 23% nurse assistants, and 58% registered nurses; hospice beds (12-25); length of stay (median = 12 days). This model predicted an up to four times greater likelihood of controlling all six ESAS-r symptoms over time. The generalized estimating equations model on the educational level of physicians and registered nurses showed that it was significantly associated with optimal patients' symptom control during the entire hospice stay. This study showed the exact skill-mix composition and proportions of palliative care team able to ensure optimal control of patients' symptoms. The added value of physicians and nurses with a qualification in palliative care in terms of better patient outcomes reaffirmed the importance of education in guaranteeing quality care. Hospices with 12-25 beds, and recruitment methods guaranteeing at least 12-day stay ensured the most propitious organizational environment for optimal management of clinically significant symptoms. The transferability of these results mainly depends on whether the skills of health professionals in our `ideal' model are present in other contexts. Our results provide policymakers and hospice managers with specific, evidence-based information to support decision-making processes regarding hospice staffing and organization. Further prospective studies are needed to confirm the positive impact of this 'optimal' organizational framework on patient outcomes.


An integrative and interactive framework for improving biomedical pattern discovery and visualization.
Recent progress in medical sciences has led to an explosive growth of data. Due to its inherent complexity and diversity, mining such volumes of data to extract relevant knowledge represents an enormous challenge and opportunity. Interactive pattern discovery and visualization systems for biomedical data mining have received relatively little attention. Emphasis has been traditionally placed on automation and supervised classification problems. Based on self-adaptive neural networks and pattern-validation statistical tools, this paper presents a user-friendly platform to support biomedical pattern discovery and visualization. It has been tested on several types of biomedical data, such as dermatology and cardiology data sets. The results indicate that in comparison to traditional techniques, such as Kohonen Maps, this platform may significantly improve the effectiveness and efficiency of pattern discovery and classification tasks, including problems described by several classes. Furthermore, this study shows how the combination of graphical and statistical tools may make these patterns more meaningful.


EGFR inhibition as a therapy for head and neck squamous cell carcinoma.
Improved understanding of disease biology of head and neck squamous cell carcinoma (HNSCC) with nearly universal expression of EGFR has led to the introduction of targeted therapies to interrupt signalling of this negative prognostic marker. We performed a literature review on the mechanisms and efficacy of anti-EGFR antibodies and EGFR tyrosine kinase inhibitors in patients with locally advanced or recurrent/metastatic HNSCC. Clinical trials in HNSCC have administered EGFR directed drugs as single agents, in combination with chemotherapy or radiotherapy and demonstrated a good safety profile with antitumour activity in a subgroup of patients. The biology of responsiveness is still unclear, although there is growing evidence of an association of skin toxicity or presence of shorter EGFR intron 1 cytosine-adenine repeats with positive outcome.


Development of a Rainbow Trout (Oncorhynchus mykiss) Intestinal In Vitro Platform for Profiling Amino Acid Digestion and Absorption of a Complete Diet.
The ever-increasing number and variation of raw materials utilized to provide alternative feed formulations continues to allow for a more sustainable and flexible approach. Testing all these options in vivo is still the most robust and reliable manner to pick the best raw material candidates, but it requires the use of large numbers of animals and is time-consuming and expensive. Therefore, we are developing an in vitro platform that can provide a reliable evaluation of new ingredients. The main aim of this work was to combine an in vitro digestion protocol of extruded, commercially relevant aquafeeds with the exposure of intestinal epithelial cells to the extracted bio-available fraction (BAF). The results show that 250,000 cells/cm2 represents the optimal seeding density and that up to 50% BAF concentration for up to 24 h had no negative effects on the epithelial barrier morphology and function. It is possible to determine amino acid digestibility and bioavailability in all the experimental conditions (with and without BSA, at 25% and 50% dilution) and at all time points (0, 6, and 24 h). However, BAF concentration, the medium used for its dilution, and the length of exposure to the different epithelial cell lines can all influence the results and, therefore, must be selected according to the final aim of the experiment.


A novel minimally-invasive method to sample human endothelial cells for molecular profiling.
The endothelium is a key mediator of vascular homeostasis and cardiovascular health. Molecular research on the human endothelium may provide insight into the mechanisms underlying cardiovascular disease. Prior methodology used to isolate human endothelial cells has suffered from poor yields and contamination with other cell types. We thus sought to develop a minimally invasive technique to obtain endothelial cells derived from human subjects with higher yields and purity. Nine healthy volunteers underwent endothelial cell harvesting from antecubital veins using guidewires. Fluorescence-activated cell sorting (FACS) was subsequently used to purify endothelial cells from contaminating cells using endothelial surface markers (CD34/CD105/CD146) with the concomitant absence of leukocyte and platelet specific markers (CD11b/CD45). Endothelial lineage in the purified cell population was confirmed by expression of endothelial specific genes and microRNA using quantitative polymerase chain reaction (PCR). A median of 4,212 (IQR: 2161-6583) endothelial cells were isolated from each subject. Quantitative PCR demonstrated higher expression of von Willebrand Factor (vWF, P<0.001), nitric oxide synthase 3 (NOS3, P<0.001) and vascular cell adhesion molecule 1 (VCAM-1, P<0.003) in the endothelial population compared to similarly isolated leukocytes. Similarly, the level of endothelial specific microRNA-126 was higher in the purified endothelial cells (P<0.001). This state-of-the-art technique isolates human endothelial cells for molecular analysis in higher purity and greater numbers than previously possible. This approach will expedite research on the molecular mechanisms of human cardiovascular disease, elucidating its pathophysiology and potential therapeutic targets.


Leading for research excellence and integrity: A qualitative investigation of the relationship-building practices of exemplary principal investigators.
We conducted semi-structured, telephone interviews with 52 federally funded researchers nominated as exemplars for their integrity and professional conduct, and their scientific achievements. The aim was to identify the practices they report utilizing to build respectful relationships in their teams. We found four practices, holding meetings, providing supervision and guidance, encouraging shared ownership, and expressing values, which were also important to performing high-quality, compliant research, were essential to fostering relationships. The most common practice described for building relationships was actively and deliberately cultivating a positive team environment. Additionally, exemplars described the need to lead by example, tailor their approach to the needs of individuals, address interpersonal conflict, and hire team members cautiously. We also identified practices the exemplars reported as important to managing the demands of their work and found that encouraging shared ownership and tailoring to individuals supported this goal. Additional strategies related to prioritization and planning, seeking advice, engaging in self-care, and managing emotional reactions. Finally, we identified priorities guiding the exemplars' practices. Key priorities included providing outstanding mentoring, building collaborations and relationships, and engaging in discovery and innovation. Investigators require exceptional leadership skills but receive limited systematic leadership training. Addressing this gap would advance research excellence and integrity.


Investigation of Heterologously Expressed Glucose-6-Phosphate Dehydrogenase Genes in a Yeast zwf1 Deletion.
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme of the oxidative part of the pentose phosphate pathway and serves as the major source of NADPH for metabolic reactions and oxidative stress response in pro- and eukaryotic cells. We here report on a strain of the model yeast Saccharomyces cerevisiae which lacks the G6PD-encoding ZWF1 gene and displays distinct growth retardation on rich and synthetic media, as well as a strongly reduced chronological lifespan. This strain was used as a recipient to introduce plasmid-encoded heterologous G6PD genes, synthesized in the yeast codon usage and expressed under the control of the native PFK2 promotor. Complementation of the hypersensitivity of the zwf1 mutant towards hydrogen peroxide to different degrees was observed for the genes from humans (HsG6PD1), the milk yeast Kluyveromyces lactis (KlZWF1), the bacteria Escherichia coli (EcZWF1) and Leuconostoc mesenteroides (LmZWF1), as well as the genes encoding three different plant G6PD isoforms from Arabidopsis thaliana (AtG6PD1, AtG6PD5, AtG6PD6). The plastidic AtG6PD1 isoform retained its redox-sensitive activity when produced in the yeast as a cytosolic enzyme, demonstrating the suitability of this host for determination of its physiological properties. Mutations precluding the formation of a disulfide bridge in AtG6PD1 abolished its redox-sensitivity but improved its capacity to complement the yeast zwf1 deletion. Given the importance of G6PD in human diseases and plant growth, this heterologous expression system offers a broad range of applications.


Openness to experience and creativity: When does global citizenship matter?
The relationship between the openness to experience trait (OTE) and creativity has been well documented in previous research. Likewise, the global citizenship construct has theoretical overlap with both OTE and creativity. We hypothesised global citizenship would make a unique contribution to explaining variance in five types of creativity (self/everyday, scholarly, performance, mechanical/scientific and artistic), above and beyond the contribution of OTE. Participants were predominantly female, European American, traditionally aged college students (N = 407). Global citizenship prosocial outcomes explained unique variance in self/everyday (sr2 = .10), scholarly (sr2 = .03) and mechanical/scientific (sr2 = .03) creativity. Results are discussed in terms of dual processes theories of cognition.


Difference in the outcome of patients managed with isolated renal injury and co-existent abdominal organ injury.
Involvement of associated intra-abdominal organs like spleen; pancreas, bowel and liver with renal injuries have a higher rate of open operative management. This is often done to avert the potential of peri-renal infection and subsequent risk of secondary hemorrhage of the injured kidney after intra-abdominal surgery. With this background we reviewed our experience to see if operative intervention for co-existing injuries to intra-abdominal organs increase the rate of nephrectomy for grade II-IV renal injuries. In the period between January 1990 and December 2000, we identified 50 patients managed in this hospital with evidence of external injury resulting in renal trauma. Patients were divided into two groups; i) Patients with isolated renal injury (group A) and ii) renal injury associated with solid abdominal organ injury (group B). The two groups were compared. The severity of renal injury was classified by using the renal injury scale (I-V), which was published by the Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A.A.S.T.). Sixty percent patients had associated organ involvement. Penetrating injuries were responsible for 47% patients in-group B compared to only 5% in group A (p < 0.001). CT was the predominant radiological investigation in both groups. Spleen was the commonest intra-abdominal organ involved (70%). Mean grade of injury in group-A was 2.2 compared to 2.7 in group B. Operative management was done in 20% patients in group A compared to 29% in group B. Nephrectomy in both groups were performed only for grade V injuries. Exploration does not increase the rate of nephrectomy; in group B grade II-IV injuries when explored were all reconstructed. Penetrating injuries are more likely to cause associated organ injuries (p < 0.001). Spleen is the commonest organ involved.


Structures and bonding of the sandwich complexes [Ti(eta5-E5)2]2- (E = CH, N, P, As, Sb): a theoretical study.
Quantum chemical calculations using gradient-corrected DFT at the BP86/TZ2P level of the compounds [Ti(eta(5)-E(5))(2)](2)(-) (E = CH, N, P, As, Sb) are reported. The nature of the metal-ligand bonding has been analyzed with an energy decomposition method, and the results are compared with [Fe(eta(5)-E(5))(2)]. The bonding in both series of complexes is more covalent than electrostatic. The energy decomposition analysis shows that the dominant orbital interactions in the negatively charged titanium species come from the (e(2)') Ti --> [(eta(5)-E(5))(2)](2)(-) back-donation (delta bonding) while the covalent bonding in the iron complexes come mainly from (e(1)' ') (Cp(-))(2) --> Fe(2+) donation (pi bonding). The nature of the metal-ligand interactions does not change very much for different ligands cyc-E(5) within the two series of compounds. The calculated bond dissociation energies for breaking one metal-ligand bond of the molecules [Ti(eta(5)-E(5))(2)](2)(-) shows for E the order P > As > Sb >> N >> CH. The central message of this work is that the complexes [Ti(eta(5)-E(5))(2)](2)(-) are delta bonded molecules.


Anxiety and depressive symptoms in caregivers of multiple sclerosis patients: The role of information processing speed impairment.
Multiple sclerosis (MS) patients have high rates of complications and disability, including cognitive impairment, that often, impact on caregivers' emotional health. Clarification may help identify improved supportive strategies for both caregivers and patients. We aimed to analyse whether MS domain-specific cognitive impairment can influence the severity of psychiatric symptoms of MS caregivers. Patients with definite MS (n=63) and their corresponding caregivers (n=63) were recruited. In addition, 59 matched controls were enrolled for establishing normative cognitive data. Each patient underwent a complete neuropsychological testing for cognitive impairment and thorough clinical assessment, including data of disability status (EDSS), affective and emotional symptoms (depression, anxiety, anger) and fatigue. Psychiatric symptoms of the caregivers were assessed with the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI). In logistic regression analyses, even after controlling for other MS-related symptoms, cognitive deficits, namely impairment on Symbol Digit Modalities Test (OR=8.03, 95% CI=1.27-25.33, p=0.027) and on the Paced Auditory Serial Addition Test (OR=6.86, 95% CI=1.07-21.97, p=0.042), were significant and independent predictors of more severe caregivers' depressive symptoms. Information processing speed impairment is independently associated with more severe depressive symptoms of caregivers of MS patients, thereby reflecting a further deterioration of family setting.


Therapeutic Potential of Isoflavones with an Emphasis on Daidzein.
Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.


Identifying Accuracy-related Outliers in a 6-Minute Walk Test Application for Monitoring Cardiovascular Disease Patients.
The 6-Minute Walk Test (6-MWT) is frequently used to evaluate functional physical capacity of patients with cardiovascular diseases. To determine reliability in remote care, outlier classification of a mobile Global Navigation Satellite System (GNSS) based 6-MWT App had to be investigated. The raw data of 53 measurements were Kalman filtered and afterwards layered with a Butterworth high-pass filter to find correlation between the resulting Root Mean Square value (RMS) outliers to relative walking distance errors using the test. The analysis indicated better performance in noise detection using all 3 GNSS dimensions with a high Pearson correlation of r = 0.77, than sole usage of elevation data with r = 0.62. This approach helps with the identification between accurate and unreliable measurements and opens a path that allows usage of the 6-MWT in remote disease management settings.Clinical Relevance- The 6-MWT is an important assessment tool of walking performance for patients with cardiovascular diseases. Using a sufficiently accurate application would enable unsupervised and easy remote usage, which could potentially reduce the demand for in-clinic visits and facilitate a more convenient and reliable monitoring method in telehealth settings.


Level of Physical Activity of Physicians Among Residency Training Program At Prince Sultan Military Medical City, Riyadh, KSA 2014.
Physical exercise is a crucial component in maintaining a healthy life. Unfortunately, the prevalence of adequate physical activity among young physicians is low. Additionally, there was a few research estimating lifestyle habits and other preventive health measurements especially during their residency-training program despite the importance of this topic. The aim of this research is to determine the level of physical activity and the main barriers of being physically active among physicians at Prince Sultan Military Medical City (PSMMC). An analytical cross-sectional study was adopted targeting the physicians of residency training program in different specialties at PSMMC, Riyadh, KSA. Data was collected using of short form of the International Physical Activity Questionnaire (IPAQ). The study showed that 68.4% of the participants had low level of physical activity (≤600-MET min/week). High physical activity level was more reported among male physicians compared to female physicians (4.3% versus 1.3%). The most frequent barriers of practicing physical activities among males were limited exercise facilities at home (71.7%), not suitable weather (69%) and the first priority is not for exercise (67.2%) whereas among females were no enough time to exercise (69.3%), lack of suitable places to exercise nearby (68%), the first priority is not for exercise (66.7%). Most of the physicians especially female residents reported low level of physical exercise due to many barriers. Overcoming these barriers may contribute to a further increase in the level of physical activity among them.


Plasma renin activity following renal transplantation.
Plasma renin activity (PRA) was studied serially for up to 21 days following transplantation in thirteen patients receiving renal allografts. PRA was measured during fasting and recumvency and its relationship to renal function, diuretic administration, plasma sodium, allograft rejection and blood pressure was examined. PRA fell steadily as renal function improved and plasma sodium rose following transplantation and when rejection episodes were excluded an inverse relationship between PRA and renal function could be seen. It is not possible to say whether the changes in PRA and function are causally related or whether changes in plasma sodium alone account for the observed changes in PRA. Some rejection episodes were accompanied by an increase in PRA, but this was not sufficiently consistent to be of value in the diagnosis of rejection. PRA also increased in relation to frusemide-induced fluid loss. There was no relationship in these patients between PRA and blood pressure.


Clinical Study of 3D Imaging and 3D Printing Technique for Patient-Specific Instrumentation in Total Knee Arthroplasty.
Patient-specific instrumentation (PSI) was designed to improve the accuracy of preoperative planning and postoperative prosthesis positioning in total knee arthroplasty (TKA). However, better understanding needs to be achieved due to the subtle nature of the PSI systems. In this study, 3D printing technique based on the image data of computed tomography (CT) has been utilized for optimal controlling of the surgical parameters. Two groups of TKA cases have been randomly selected as PSI group and control group with no significant difference of age and sex (p > 0.05). The PSI group is treated with 3D printed cutting guides whereas the control group is treated with conventional instrumentation (CI). By evaluating the proximal osteotomy amount, distal osteotomy amount, valgus angle, external rotation angle, and tibial posterior slope angle of patients, it can be found that the preoperative quantitative assessment and intraoperative changes can be controlled with PSI whereas CI is relied on experience. In terms of postoperative parameters, such as hip-knee-ankle (HKA), frontal femoral component (FFC), frontal tibial component (FTC), and lateral tibial component (LTC) angles, there is a significant improvement in achieving the desired implant position (p < 0.05). Assigned from the morphology of patients' knees, the PSI represents the convergence of congruent designs with current personalized treatment tools. The PSI can achieve less extremity alignment and greater accuracy of prosthesis implantation compared against control method, which indicates potential for optimal HKA, FFC, and FTC angles.


A four-pole SAW resonator filter combining transverse and symmetrical longitudinal modes.
As a continuation of the activities concerning longitudinal and transverse modes, this paper describes the combination of transverse and neighboring longitudinal modes with the same symmetry for designing a four-pole resonator filter. The construction of both interdigital transducers arranged side by side agrees and is characterized by a symmetrical withdrawing weighting. The present solution offers the advantage to achieve a wider bandwidth for the same layout dimensions compared with the principle using neighboring longitudinal modes of different symmetry. The applicability of the principle to the filter design is demonstrated by experimental measurements.


Retinal degeneration associated with taurine deficiency in the cat.
A degeneration of the retinal photoreceptor cells develops in cats when casein is the source of dietary protein. Amino acid profiles indicate that the degeneration is associated with a selective decrease in plasma and retinal taurine concentrations. A sulfur amino acid deficit in the casein diet combined with specific amino acid requirements of the cat appear related to this unique expression of taurine deficiency.


Efficient gonio-imaging of optically variable devices by compound-eye image-capturing system.
In this paper, we propose a method for efficient gonio-imaging of optically variable devices (OVDs), which are applied as a counterfeit deterrence for valuable documents. A compound-eye image-capturing system composed by a microlens array, a signal separator, and an image sensor was used to capture directionally distributed light from OVDs after being collimated by a convex lens. Multiple images corresponding to different observation angles were obtained in the individual eyes of the system, simultaneously and independently. A demonstration involving a holographic grating provided 100 gonio images that exhibited sensitive color changes of the diffracted light according to the observation angle.


Treatment of genital warts by cryosurgery--a follow-up study.
This is a follow-up study involving 50 patients who were treated as outpatients for genital warts using cryosurgery. Single and multiple lesions involving the vulva, vagina and cervix were treated. A cryoprobe cooled to minus 70 degrees centigrade by liquid carbon dioxide and applied to the lesion for 2 1/2 to 3 minutes was used in the treatment. Nine pregnant patients in this study treated with cryosurgery did not experience any adverse effects on their pregnancies. There were no adverse side effects noted among the rest of the patients. All the patients with single wart were treated successfully with cryosurgery whereas those with multiple lesions were successfully treated in only 82 per cent of the patients. Four patients did not respond to treatment. Recurrence after cryosurgery within 3 months of therapy was noted in 2 patients. In conclusion, the treatment of genital warts by cryosurgery was found to be a safe and effect procedure.


Tunnelling nanotube formation is driven by Eps8/IRSp53-dependent linear actin polymerization.
Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy, and optical tweezer-based approaches, we demonstrate that TNTs formed through the outward extension of actin achieve distances greater than the mean length of filopodia and that branched Arp2/3-dependent pathways attenuate the extent to which actin polymerizes in nanotubes, thus limiting their occurrence. Proteomic analysis using epidermal growth factor receptor kinase substrate 8 (Eps8) as a positive effector of TNTs showed that, upon Arp2/3 inhibition, proteins enhancing filament turnover and depolymerization were reduced and Eps8 instead exhibited heightened interactions with the inverted Bin/Amphiphysin/Rvs (I-BAR) domain protein IRSp53 that provides a direct connection with linear actin polymerases. Our data reveals how common protrusion players (Eps8 and IRSp53) form tunnelling nanotubes, and that when competing pathways overutilizing such proteins and monomeric actin in Arp2/3 networks are inhibited, processes promoting linear actin growth dominate to favour tunnelling nanotube formation.


Genome-wide sequence-based prediction of peripheral proteins using a novel semi-supervised learning technique.
In supervised learning, traditional approaches to building a classifier use two sets of examples with pre-defined classes along with a learning algorithm. The main limitation of this approach is that examples from both classes are required which might be infeasible in certain cases, especially those dealing with biological data. Such is the case for membrane-binding peripheral domains that play important roles in many biological processes, including cell signaling and membrane trafficking by reversibly binding to membranes. For these domains, a well-defined positive set is available with domains known to bind membrane along with a large unlabeled set of domains whose membrane binding affinities have not been measured. The aforementioned limitation can be addressed by a special class of semi-supervised machine learning called positive-unlabeled (PU) learning that uses a positive set with a large unlabeled set. METHODS In this study, we implement the first application of PU-learning to a protein function prediction problem: identification of peripheral domains. PU-learning starts by identifying reliable negative (RN) examples iteratively from the unlabeled set until convergence and builds a classifier using the positive and the final RN set. A data set of 232 positive cases and ~3750 unlabeled ones were used to construct and validate the protocol. Holdout evaluation of the protocol on a left-out positive set showed that the accuracy of prediction reached up to 95% during two independent implementations. These results suggest that our protocol can be used for predicting membrane-binding properties of a wide variety of modular domains. Protocols like the one presented here become particularly useful in the case of availability of information from one class only.


Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM.
Use of monoclonal antibodies directed against rat macrophages and serial pancreatic biopsy in the prediabetic period have enabled us to document the involvement of macrophages in the pancreatic events leading to onset of diabetes in the spontaneously diabetic BB/E rat. A few weeks before onset of disease, there is marked recruitment and accumulation of ED1+ macrophages at periductal and perivascular locations adjacent to noninfiltrated islets. These recruited cells, distinct from the resident ED2+ tissue macrophages, then infiltrate the islets. Infiltration of the pancreas by ED1+ macrophages is therefore a very early event in the prediabetic period and suggests a possible role for macrophages in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in this animal model.


[Vanadium content in the hair and chosen lipid indices in the blood serum of students of the Bialystok Medical Academy].
It was examined whether the vanadium content in the organism estimated on the basis of its concentration in the hair of students of the Białystok Medical Academy was related to lipid metabolism evaluated using blood lipidograms. Total cholesterol, HDL and LDL-cholesterol fractions, and triglycerides were determined by the reflectrometric method, using a Reflotron apparatus, Roche. Vanadium concentration in the hair was measured by atomic absorption spectrophotometry, with a Hitachi Z-5000 apparatus, following sample incineration and dissolution in a 1 M solution of spectrally pure HNO3. The results were verified basing on the reference material (hair). The mean vanadium content in the hair of women was 0.032 microgram/g of hair, being higher than its concentration in the hair of men-0.019 microgram/g of hair. The difference was statistically significant. Lipid concentration in the blood serum of the subjects examined showed no statistically significant differences according to gender. Lipid indices were, however, markedly higher in women.


Autotransplantation of Third Molars With Platelet-Rich Plasma for Immediate Replacement of Extracted Non-Restorable Teeth: A Case Series.
The aim of this study was to examine the use of platelet-rich plasma (PRP) for autotransplantation of third molars as a successful technique to provide immediate tooth structure for space maintenance and masticatory function when premature loss of a permanent tooth occurs and other dental restorative options are not indicated. This study included 10 healthy patients 10 to 17 years of age with at least 1 immature third molar (one to two thirds of root formation) used to replace extracted non-restorable teeth. Eleven third molars were transplanted and adapted to sockets of the extracted teeth with the adjunct of PRP. Transplanted teeth were stabilized to the adjacent teeth using orthodontic wires and dental composite for 1 month. Patients were followed for 1 year. Function, tooth vitality, root development, and periodontal health were recorded. All 10 patients had functioning asymptomatic transplanted teeth, with physiologic tooth mobility after splint removal at 1 month and after 1 year. All 10 patients had positive tooth vitality (by cold test) at 3, 6, and 12 months; all transplants showed positive root development (average growth, 2.01 mm) confirmed and measured using periapical radiographs. No patients required root canal therapy at any point in the study. Periodontal assessments were performed at the scheduled follow-up appointments with circumferential periodontal probing. Periodontal health was maintained because probing depths were shallower than 4 mm during the 1-year follow-up. Autotransplantation of immature third molars with PRP shows excellent results and should be considered a viable option for premature loss of permanent molars. PRP might have other advantages, such as root promotion and neurosensory development.


Computational and experimental investigation of the effect of cation structure on the solubility of anionic flow battery active-materials.
Recent advances in clean, sustainable energy sources such as wind and solar have enabled significant cost improvements, yet their inherent intermittency remains a considerable challenge for year-round reliability demanding the need for grid-scale energy storage. Nonaqueous redox flow batteries (NRFBs) have the potential to address this need, with attractive attributes such as flexibility to accommodate long- and short-duration storage, separately scalable energy and power ratings, and improved safety profile over integrated systems such as lithium-ion batteries. Currently, the low-solubility of NRFB electrolytes fundamentally limits their energy density. However, synthetically exploring the large chemical and parameter space of NRFB active materials is not only costly but also intractable. Here, we report a computational framework, coupled with experimental validation, designed to predict the solubility trends of electrolytes, incorporating both the lattice and solvation free energies. We reveal that lattice free energy, which has previously been neglected, has a significant role in tuning electrolyte solubility, and that solvation free energies alone is insufficient. The desymmetrization of the alkylammonium cation leading to short-chain, asymmetric cations demonstrated a modest increase in solubility, which can be further explored for NRFB electrolyte development and optimization. The resulting synergistic computational-experimental approach provides a cost-effective strategy in the development of high-solubility active materials for high energy density NRFB systems.


Cost Analysis of Teleophthalmology Screening for Diabetic Retinopathy Using Teleophthalmology Billing Codes.
To evaluate the financial sustainability of teleophthalmology screening for diabetic retinopathy (DR) using telehealth billing codes. The authors performed an Institutional Review Board-approved retrospective review of medical records, billing data, and quality metrics at the University of California Davis Health System from patients screened for DR through an internal medicine-based telemedicine program using CPT codes 92227 or 92228. A total of 290 patients received teleophthalmology screening over a 12-month period, resulting in an increase in the DR screening rate from 49% to 63% (P < .0001). The average payment per patient was $19.86, with an estimated cost of $41.02 per patient. The projected per-patient incentive bonus was $43.06 with a downstream referral revenue of $39.38 per patient. One hundred seventy-eight clinic visits were eliminated, providing an estimated cost savings of $42.53 per patient. Sustainable teleophthalmology screening may be achieved by billing telehealth codes but only with health care incentive bonuses, patient referrals, and by accounting for the projected cost-savings of eliminating office visits. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S26-S34.].


A Ca2+ influx associated with exocytosis is specifically abolished in a Paramecium exocytotic mutant.
A Paramecium possesses secretory organelles called trichocysts which are docked beneath the plasma membrane awaiting an external stimulus that triggers their exocytosis. Membrane fusion is the sole event provoked by the stimulation and can therefore be studied per se. Using 3 microM aminoethyl dextran (AED; Plattner, H., H. Matt, H.Kersken, B. Haake, and R. Stürz, 1984. Exp. Cell Res. 151:6-13) as a vital secretagogue, we analyzed the movements of calcium (Ca2+) during the discharge of trichocysts. We showed that (a) external Ca2+, at least at 3 X 10(-7) M, is necessary for AED to induce exocytosis; (b) a dramatic and transient influx of Ca2+ as measured from 45Ca uptake is induced by AED; (c) this influx is independent of the well-characterized voltage-operated Ca2+ channels of the ciliary membranes since it persists in a mutant devoid of these channels; and (d) this influx is specifically abolished in one of the mutants unable to undergo exocytosis, nd12. We propose that the Ca2+ influx induced by AED reflects an increase in membrane permeability through the opening of novel Ca2+ channel or the activation of other Ca2+ transport mechanism in the plasma membrane. The resulting rise in cytosolic Ca2+ concentration would in turn induce membrane fusion. The mutation nd12 would affect a gene product involved in the control of plasma membrane permeability to Ca2+, specifically related to membrane fusion.


International trade resilience and the Covid-19 pandemic.
The Covid-19 pandemic represents a low-probability, high-impact systemic risk that has severely disrupted international trade, reshaping the patterns of globalization. Drawing from the concept of supply chain resilience, which involves both the ability of a system to withstand an impact (robustness) and recover from it (responsiveness), we investigate country-level trade resilience during the 1st wave of the pandemic. By employing Fuzzy-set Qualitative Comparative Analysis (fsQCA), we identify configurations of country-level factors, i.e., country profiles, based on their effectiveness in engendering trade resilience. These factors include social and economic globalization, logistics performance, healthcare preparedness, national government response, and income level. The results show how these factors coalesced to strengthen (or weaken) international trade resilience, contributing to a holistic understanding of the impact of the pandemic on international trade. The findings inform the post-Covid-19 debate on international trade, with implications for managers and policymakers.


The Incidental Use of High-Dose Vitamin D3 in Pancreatic Cancer.
Background: Pancreatic adenocarcinoma is associated with a very poor prognosis, with a 5 year survival of ∼7.2%. Vitamin D has long been evaluated for benefit as a protective agent and treatment for malignancies. Although cancer incidence and outcomes have been tied to vitamin D levels, there is no clear evidence that supplementation of vitamin D improves outcome in pancreatic cancer to date. Case Presentation: We present a patient who errantly took supratherapeutic doses of vitamin D 50,000 U daily, achieving a serum 25(OH)D level of more than 150 mg/mL, with no appreciable side effects. Conclusion: Her disease was stable for 8 months off of conventional treatment, although it is unclear whether this was related to vitamin D supplementation.


Effectiveness of an individual, online e-learning program about sexually transmitted infections: a prospective cohort study.
Primary health-care professionals play an important role in the treatment and prevention of Sexually Transmitted Infections (STI). Continuing Medical Education (CME)-courses can influence the knowledge and behavior of health-care professionals concerning STI. We performed a prospective cohort study to evaluate if the individual and online e-learning program "The STI-consultation", which uses the Commitment-to-Change (CtC)-method, is able to improve the knowledge, attitude and behavior of Dutch General Practitioners (GPs), concerning the STI-consultation. This e-learning program is an individual, accredited, online CME-program, which is freely available for all GPs and GP-trainees in the Netherlands. In total 2192 participants completed the questionnaire before completing the e-learning program and 249 participants completed the follow-up questionnaire after completing the e-learning program. The effect of the program on their knowledge, attitude and behavior concerning the STI-consultation was evaluated. In total 193 participants formulated 601 learning points that matched the learning objectives of the program. The knowledge and attitude of the participants improved, which persisted up to two years after completing the program. Another 179 participants formulated a total of 261 intended changes concerning the sexual history taking, additional investigation and treatment of STI, 97.2% of these changes was partially or fully implemented in daily practice. Also, 114 participants formulated a total of 180 "unintended" changes in daily practice. These changes concerned the attitude of participants towards STI and the working conditions concerning the STI-consultation. The individual, online e-learning program "The STI-consultation", which uses the CtC-method, has a small but lasting, positive effect on the knowledge, attitude, and behavior of GPs concerning the STI-consultation.


What proportion of international travellers acquire a travel-related illness? A review of the literature.
As international travel increases, travellers may be at increased risk of acquiring infectious diseases not endemic in their home countries. Many journal articles and reference books related to travel medicine cite that between 22-64% of international travellers become ill during or after travel; however, this information is minimal, outdated and limited by poor generalizability. We aim to provide a current and more accurate estimate of the proportion of international travellers who acquire a travel-related illness. We identified studies via PubMed or travel medicine experts, published between January 1, 1976-December 31, 2016 that included the number of international travellers acquiring a travel-related illness. We excluded studies that focused on a single disease or did not determine a rate based on the total number of travellers. We abstracted information on traveller demographics, trip specifics, study enrollment and follow-up and number of ill travellers and their illnesses. Of 743 studies, nine met the inclusion criteria. The data sources were from North America (four studies) and Europe (five studies). Most travellers were tourists, the most frequent destination regions were Asia and Africa, and the median trip duration ranged from 8-21 days. Six studies enrolled participants at the travellers' pre-travel consultation. All studies collected data through either extraction from the medical record, weekly diaries, or pre- and post-travel questionnaires. Data collection timeframes varied by study. Between 6-87% of travellers became ill across all studies. Four studies provided the best estimate: between 43-79% of travellers who frequently visited developing nations (e.g. India, Tanzania, and Kenya) became ill; travellers most frequently reported diarrhoea. This is the most comprehensive assessment available on the proportion of international travellers that develop a travel-related illness. Additional cohort studies would provide needed data to more precisely determine the rates of illness in international travellers. International travel, travel, illness.


Bedside Lung Ultrasound in Emergency Protocol as a Diagnostic Tool in Patients of Acute Respiratory Distress Presenting to Emergency Department.
The objective of this study is to determine the accuracy of the bedside lung ultrasound in emergency (BLUE) protocol in giving a correct diagnosis in patients presenting with acute respiratory distress in emergency department. Patients with acute respiratory distress were evaluated. Ultrasound findings such as artifacts (A line, B line), lung sliding, alveolar consolidation or pleural effusion, and venous analysis were recorded. Ultrasonography findings were correlated with final diagnosis made by the treating unit. Sensitivity and specificity were calculated. A total 50 patients were evaluated. The A profile (predominant A line with lung sliding) indicated chronic obstructive pulmonary disease/asthma (n = 14) with 85.17% sensitivity and 88.88% specificity. B profile (predominant B + lines with lung sliding) indicated pulmonary edema (n = 13) with 92.30% sensitivity and 100% specificity. The A/B profile (A line on one side and B + line on other side) and the C profile (anterior consolidation) and the A profile plus posterolateral alveolar and/or pleural syndrome indicated pneumonia (n = 17) with 94.11 sensitivity and 93.93% specificity. The A profile plus venous thrombosis indicated pulmonary embolism (n = 1) with 100% sensitivity and specificity. A' profile (predominant A line without lung sliding) with lung point indicated pneumothorax (n = 5) with 80% sensitivity and 100% specificity. BLUE protocol was successful in average 90.316% cases. BLUE performed in emergency department is equivalent to computed tomography scan. BLUE protocol aids in making diagnosis and saves time and cost; avoids the side effects related to radiation.


In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.
We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.


Polarized light examination and photography of the skin.
Light reflected from skin has two components: regular reflectance, or "glare" arising from the surface, and light backscattered from within the tissue. The regular reflectance contains the visual cues related to surface texture, whereas the backscattered component contains the cues related to pigmentation, erythema, infiltrates, vessels, and other intracutaneous structures. Unlike the backscattered component, regular reflectance preserves the plane of polarization of polarized incident light. Thus, viewing skin through a linear polarizer, under linearly polarized illumination, separates the two components of tissue reflectance. Thirty patients were examined and photographed in this manner. When the planes of polarization are parallel, images with enhanced surface detail are obtained. When the planes are orthogonal, wrinkles and surface detail disappear, and an enhanced view of vasculature and pigmented lesions is obtained. Simple, clinically useful techniques are presented.


Tyrosine kinase inhibitors induce alternative spliced BCR-ABLIns35bp variant via inhibition of RNA polymerase II on genomic BCR-ABL.
To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABLIns35bp , accounting for 0.8% of the total IS BCR-ABL, corresponding to actual BCR-ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR-ABL but not BCR-ABLIns35bp , leading to the initial increase in the proportion of BCR-ABLIns35bp . Thereafter, both native BCR-ABL and BCR-ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI-resistant BCR-ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR-ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function-dead BCR-ABLIns35bp , suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis-splicing BCR-ABLIns35bp , occurring at the particular pseudo-splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR-ABL extracting BCR-ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.


Measuring design thinking competence in Taiwanese nursing students: a cross-cultural instrument adaptation.
Design thinking (DT) competence, a creative problem-solving ability, has been investigated extensively among college students in various professional fields within the western cultures. No instrument, however, is available for assessing DT competence in nursing students, particularly, those in non-western cultures. To adapt and validate the use of Creative Synthesis Inventory (CSI) assessing the four components (i.e., visualization, discovery, prototyping, and evaluation) of DT competence in nursing students in Taiwan. Cross-sectional, mixed methodological design combining qualitative and quantitative strategies. A 19-item CSI was administered to a total of 520 nursing students from two campuses of a science and technology university in Taiwan. The data collection was conducted between September 2020 and June 2022. The cross-cultural adaptation and validation of CSI-Taiwan was done in two phases: Phase I included content validity check, translation, and cross-cultural adaptation. Phase II involved pilot testing and psychometric evaluation. A first-order confirmatory factor analysis validated the four-component structure, namely visualization, discovery, prototyping, and evaluation, of an 18-item CSI-Taiwan (model fit indices: χ2/df = 3.953, NNFI = 0.942, CFI = 0.956, TLI = 0.947, SRMR = 0.035, and RMSEA = 0.075). A second-order confirmatory factor analysis further indicated that the four components converged on a unitary construct of DT competence (model fit indices: χ2/df = 4.082, NNFI = 0.935, CFI = 0.949, TLI = 0.940, SRMR = 0.040, and RMSEA = 0.080). Moreover, the CSI-Taiwan also demonstrated satisfactory reliability and validity. Together these results validated the construct of DT competence and its components as theorized. The CSI-Taiwan was a reliable and valid self-report instrument to be used by Taiwanese nursing students.


Making more matrix: enhancing the deposition of dermal-epidermal junction components in vitro and accelerating organotypic skin culture development, using macromolecular crowding.
Skin is one of the most accessible tissues for experimental biomedical sciences, and cultured skin cells represent one of the longest-running clinical applications of stem cell therapy. However, culture-generated skin mimetic multicellular structures are still limited in their application by the time taken to develop these constructs in vitro and by their incomplete differentiation. The development of a functional dermal-epidermal junction (DEJ) is one of the most sought after aspects of cultured skin, and one of the hardest to recreate in vitro. At the DEJ, dermal fibroblasts and epidermal keratinocytes interact to form an interlinked basement membrane of extracellular matrix (ECM), which forms as a concerted action of both keratinocytes and fibroblasts. Successful formation of this basement membrane is essential for take and stability of cultured skin autografts. We studied interactive matrix production by monocultures and cocultures of primary human keratinocytes and fibroblasts in an attempt to improve the efficiency of basement membrane production in culture using mixed macromolecular crowding (mMMC); resulting ECM were enriched with the deposition of collagens I, IV, fibronectin, and laminin 332 (laminin 5) and also in collagen VII, the anchoring fibril component. Our in vitro data point to fibroblasts, rather than keratinocytes, as the major cellular contributors of the DEJ. Not only did we find more collagen VII production and deposition by fibroblasts in comparison to keratinocytes, but also observed that decellularized fibroblast ECM stimulated the production and deposition of collagen VII by keratinocytes, over and above that of keratinocyte monocultures. In confrontation cultures, keratinocytes and fibroblasts showed spontaneous segregation and demarcation of cell boundaries by DEJ protein deposition. Finally, mMMC was used in a classical organotypic coculture protocol with keratinocytes seeded over fibroblast-containing collagen gels. Applied during the submerged phase, mMMC was sufficient to accelerate the emergence of collagen VII along the de novo DEJ, together with stronger transglutaminase activity in the neoepidermis. Our findings corroborate the role of fibroblasts as important players in producing collagen VII and inducing collagen VII deposition in the DEJ, and that macromolecular crowding leads to organotypic epidermal differentiation in tissue culture in a significantly condensed time frame.


Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A, G:G:A:A, and A:A:A:A tetrads.
Replacement of two to four guanines by adenines in the human telomere DNA repeat dG3(TTAG3)3 did not hinder the formation of quadruplexes if the substitutions took place in the terminal tetrad bridged by the diagonal loop of the intramolecular antiparallel three-tetrad scaffold, as proved by CD and PAGE in both Na+ and K+ solutions. Thermodynamic data showed that, in Na+ solution, the dG3(TTAG3)3 quadruplex was destabilized, the least by the two G:A:G:A tetrads, the most by the G:G:A:A tetrad in which the adenosines replaced syn-guanosines. In physiological K+ solution, the highest destabilization was caused by the 4A tetrad. In K+, only the unmodified dG3(TTAG3)3 quadruplex rearranged into a K+-dependent quadruplex form, none of the multiple adenine-modified structures did so. This may imply biological consequences for nonrepaired A-for-G mutations.


Spinal cord injury in children: long-term urodynamic and urological outcomes.
Urological complications in adults with spinal cord injuries (SCIs) are well documented. We sought to determine the effect of SCI on the developing bladder and kidneys in the child. We retrospectively reviewed cases of SCI with 1-year minimum followup. We identified 42 children with an average age at injury of 5.3 years (range 1 day to 14 years). Mean followup was 5.5 years (range 1 to 15.5). Videourodynamics, sonograms, infection, medications and continence were reviewed. Safe bladder capacity was defined as the pressure specific volume at 40 cm water or less. Patients were divided into 3 groups based on level of injury-cervical (10), thoracic (26) and lumbar (6). Bladder management included clean intermittent catheterization in 40 of 42 patients and antispasmodics in 37. No patient had reflux, hydronephrosis or renal scarring. In the cervical group safe bladder capacity was less than the expected capacity in 80% of patients but all patients undergoing multiple urodynamics had increasing capacity with time. In the thoracic group 58% of patients had a safe bladder capacity less than expected and 76% of those undergoing multiple urodynamics had increasing capacity. In the lumbar group 50% of patients had a safe bladder capacity less than expected and 67% of those undergoing multiple urodynamics had increasing capacity. To our knowledge this is the largest and longest urological study of young children with SCI. Early clean intermittent catheterization and use of anticholinergics appear to prevent upper tract deterioration, improve continence and decrease infections. Serial urodynamics confirm increasing safe capacity with growth in most children. Close followup is necessary as bladder characteristics may change with time.


Association of serum lipids with β-cell function in obese children and adolescents.
Few data are available on the association between serum lipids and insulin secretion (ISEC) in children. We evaluated the association of triglycerides (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) with ISEC in 1150 non-diabetic obese children and adolescents using multivariable robust median regression. The following models were employed: (1) IGI or incAUCR as the ISEC response variable; (2) QUICKI, OGIS, the Stumvoll index or the Matsuda insulin sensitivity index as the insulin sensitivity (ISEN) predictor; (3) TG, HDL-C and LDL-C as the predictors of interest; (4) 120-min glucose, age, sex and body mass index as confounders. LDL-C and TG were not associated with ISEC in any model. In three out of four IGI models, an increase of 1 interquartile range (IQR) of HDL-C was associated with a decrease of median incAUCR ranging from -9 (robust 95% CI -17 to -2) to -8 (-14 to -1) pmol/mmol. In two out of four incAUCR models, an increase of 1 IQR of HDL-C was associated with a decrease of median IGI ranging from -8 (-15 to -1) to -7 (-11 to -2) pmol/mmol. TG and LDL-C are not associated and HDL-C is inversely associated with ISEC in obese children and adolescents.


nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial.
The phase III MPACT trial in patients with metastatic pancreatic cancer (MPC) demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) compared with Gem monotherapy, including the primary endpoint of overall survival (OS; median 8.7 vs. 6.6 months; hazard ratio [HR] 0.72; P < 0.001). A significant treatment difference favoring nab-P + Gem over Gem was observed for OS in patients treated in North America. The majority of patients were from the US (88%) with only 12% from Canada. Healthcare systems and treatment patterns are different between the 2 countries, and there is limited published information on outcomes of Canadian patients treated with first-line nab-P + Gem. This analysis evaluated efficacy and safety outcomes in Canadian patients in the MPACT trial. Treatment-naive patients with MPC (N = 861) received either nab-P 125 mg/m(2) + Gem 1000 mg/m(2) on days 1, 8, and 15 every 4 weeks or Gem 1000 mg/m(2) weekly for the first 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle ≥2). The MPACT trial enrolled 63 patients in Canada. Baseline characteristics were well balanced and comparable with those of the intent-to-treat population. Both OS (median 11.9 vs. 7.1 months; HR 0.76; P = 0.373) and progression-free survival (median 7.2 vs. 5.2 months; HR 0.65; P = 0.224) were numerically longer and overall response rate (27% vs. 17%; P = 0.312) was numerically higher with nab-P + Gem vs. Gem. The most common grade ≥3 adverse events with nab-P + Gem vs. Gem were neutropenia (22% vs. 10%), fatigue (34% vs. 33%), and neuropathy (25% vs. 0%). This subanalysis confirmed that nab-P + Gem is an efficacious treatment option and has a manageable safety profile in patients with MPC treated in Canada. ClinicalTrials.gov identifier, NCT00844649. Celgene Corporation, Summit, NJ, USA.


Variation in response among individuals to antigenic sites on the HA protein of human influenza virus may be responsible for the emergence of drift strains in the human population.
Eight convalescent human sera obtained from patients aged 3 to 14 years old, who were infected with influenza A(H3N2) virus during the 1990/1991 influenza season, were characterized by a binding assay with chimeric hemagglutinin (HA) proteins between influenza virus A/Aichi/2/68 and A/Kamata/14/91(H3N2) strains. These sera did not recognize the HA protein of the A/Aichi/2/68 strain but recognized that of the A/Kamata/14/91 strain. The binding assay revealed that these sera recognized only the HA1 domain of A/Kamata/14/91 HA protein. A further assay of the binding of these sera to the chimeric proteins of the HA1 domain revealed that three sera (A-1, A-2, and A-3) from very young patients bound only to region 150-170 (site B1) and one serum (Y-1) bound to regions 96-150 (site A) and 96-170 (sites A and B1). These four sera showed reduced hemagglutination inhibition (HI) activity with the 203v2 strain, a monoclonal variant of the A/Kamata/14/91 strain with two amino acid changes in the HA protein at antigenic sites A and B1. The other four sera (Y-2, G-1, G-2, and A-4) bound to regions 1-96 (site C/E), 96-150 (site A), 96-170 (sites A and B1), and 170-200 (site B2), two of which further bound to region 240-306 (site C); these sera were all fully reactive with the 203v2 strain. All eight sera showed reduced HI reactivity to a drift strain A/Aichi/4/93. Amino acid changes of the A/Aichi/4/93 strain from the A/Kamata/14/91 strain were located at antigenic sites A, B1, B2, and C. We propose a possible model for the emergence of a drift strain A/Aichi/4/93 from an A/Kamata/14/91-like strain by sequential changes during reinfections of individuals starting from A-1-like, next to Y-1-like, and then to Y-2-like populations.


Inverse Psoriasis: From Diagnosis to Current Treatment Options.
Inverse psoriasis represents a clinical variant of psoriasis that is sometimes difficult to diagnose due to its clinical similarity with other skin disorders involving the folds, mainly including mechanical intertrigo, fungal and bacterial infections, contact dermatitis, seborrheic dermatitis, and lichen planus. Dermoscopy represents a useful tool for an enhanced non-invasive diagnosis. The treatment of inverse psoriasis may be challenging and include topical corticosteroids, topical calcineurin inhibitors, vitamin D analogs, traditional oral systemic therapies such as cyclosporine and methotrexate, and biologic therapies.


Concurrent multicentric hemangiosarcoma and ovarian teratoma in an aged Père david's deer (Elaphurus davidianus).
A 20-yr-old female Père David's deer (Elaphurus davidianus) died following a 3-wk history of depression, anorexia, and progressive respiratory distress. At necropsy, numerous soft to firm, tan or blood-filled nodular structures, 1-6 cm in diameter, were noted in the lung and the visceral and parietal pleura and within the mediastinum. Similar nodules were also found in the liver, spleen, kidney, and lymph nodes. Histologically, the nodules were diagnosed as hemangiosarcoma. A benign teratoma was present in the left ovary.


Effects of the mode of addition of acyl-CoA on the initial rate of formation of acylcarnitine in the presence of carnitine by intact rat liver mitochondria in vitro.
Time courses for the formation of palmitoylcarnitine from palmitoyl-CoA and carnitine, catalysed by the overt activity of carnitine palmitoyltransferase (CPT I) in rat liver mitochondria, were obtained. Significant initial non-linearity was observed only when reactions were started by addition of a concentrated solution of palmitoyl-CoA (4mM, to give a final concentration of 100 microM) uncomplexed to albumin. Minimal effects were observed when the reactions were started by addition of palmitoyl-CoA-albumin mixtures, even though the final palmitoyl-CoA/albumin molar ratios in the assay medium were identical in the two sets of experiments.


Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.
Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.


Tamoxifen improves cytopathic effect of oncolytic adenovirus in primary glioblastoma cells mediated through autophagy.
Oncolytic gene therapy using viral vectors may provide an attractive therapeutic option for malignant gliomas. These viral vectors are designed in a way to selectively target tumor cells and spare healthy cells. To determine the translational impact, it is imperative to assess the factors that interfere with the anti-glioma effects of the oncolytic adenoviral vectors. In the current study, we evaluated the efficacy of survivin-driven oncolytic adenoviruses pseudotyping with adenoviral fiber knob belonging to the adenoviral serotype 3, 11 and 35 in their ability to kill glioblastoma (GBM) cells selectively without affecting normal cells. Our results indicate that all recombinant vectors used in the study can effectively target GBM in vitro with high specificity, especially the 3 knob-modified vector. Using intracranial U87 and U251 GBM xenograft models we have also demonstrated that treatment with Conditionally Replicative Adenovirus (CRAd-S-5/3) vectors can effectively regress tumor. However, in several patient-derived GBM cell lines, cells exhibited resistance to the CRAd infection as evident from the diminishing effects of autophagy. To improve therapeutic response, tumor cells were pretreated with tamoxifen. Our preliminary data suggest that tamoxifen sensitizes glioblastoma cells towards oncolytic treatment with CRAd-S-5/3, which may prove useful for GBM in future experimental therapy.


Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells.
The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin (DXR) or Nutlin-3 (Nutlin) led to strikingly different p53 gene binding patterns based on chromatin immunoprecipitation with high-throughput sequencing experiments. Although two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was six times greater for Nutlin than DXR, expression changes induced by Nutlin were much less dramatic compared with DXR. Unexpectedly, the solvent dimethylsulphoxide (DMSO) alone induced p53 binding to many sites common to DXR; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification histone H3 lysine 4 trimethylation. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network.


Chronic circadian shift leads to adipose tissue inflammation and fibrosis.
The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance.


General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes.
Type 1 diabetes (T1D) is a serious diagnosis with the prospect of grave short- and long-term complications and even death if poorly managed. An attempt has been made to describe how clinical and immunological deviations might influence each other close to the diagnosis of T1D. Sixty-nine newly diagnosed T1D children were studied together with a reference group of 30 healthy children. Cytokines (interleukin (IL)-6, IL-10, IL-13, IL-17, interferon-γ, and tumor necrosis factor-α) were detected in in vitro culture by multiplex fluorochrome technique. Information of clinical status of the patients such as BMI, weight loss, pubertal stage, duration of symptoms, previous and/or ongoing infections, insulin requirement, and ketoacidosis were gathered together with the analysis of C-peptide and glycosylated hemoglobin (HbA1c). In general, low cytokine secretion was found at diagnosis of T1D. However, high C-peptide, short duration of symptoms, or an infection prior to diagnosis was associated with increased immune activity including proinflammatory, Th2-associated, and Tr1-associated cytokines. In contrast, ketoacidosis and later pubertal stage at onset of disease were more related to a Th1-prone response. There is a general immune dampening at diagnosis of T1D, which appears to be related to the metabolic state close to diagnosis.


Rapid Novel Facile Biosynthesized Silver Nanoparticles From Bacterial Release Induce Biogenicity and Concentration Dependent In Vivo Cytotoxicity With Embryonic Zebrafish-A Mechanistic Insight.
In this study, rapid one step facile synthesis of silver nanoparticles (AgNPs) was done using culture supernatant of two Gram positive (B. thuringiensis and S. aureus) and Gram negative (E. coli and Salmonella typhimurium [STAgNP]) bacterial strains and were termed as "Bacillus thuringiensis," "Staphylococcus aureus," "Escherichia coli," and "STAgNP," respectively. Synthesized AgNPs were well characterized with the help of different standard techniques like FESEM, DLS, UV-Vis spectroscopy, and Fourier transform infrared. Mechanism of AgNPs synthesis was elucidated using in silico approach. In vivo cytotoxicity of synthesized AgNPs was assessed in embryonic Zebrafish model with the help of uptake, oxidative stress, and apoptosis induction experimental assays, and the mechanism was investigated through in silico approach at the molecular level. The result showed successful biosynthesis of 20-40 nm sized AgNPs stable with zeta potential of - 45 to - 35 mV having standard silver nanoparticles SPR peaks due to the interaction of reduced silver particles with amino acid residues of bapA proteins of the bacterial supernatant. In vivo cytotoxicity with embryonic Zebrafish was found to be dependent on biogenicity and concentration of biosynthesized AgNPs as consequence of oxidative stress induction and apoptosis due to the influential regulation of sod1 and tp53 genes clarified by pathway analysis with reference to experimental and computational results. The study suggested that cytotoxicity of biologically synthesized silver nanoparticles from bacteria depends on strain specificity with significant difference in use of Gram positive and Gram negative bacterial strains.


Ginsenoside Rg3 inhibits cell growth, migration and invasion in Caco-2 cells by downregulation of lncRNA CCAT1.
Colorectal cancer (CRC) is a troublesome disease with high morbidity and mortality. Ginsenoside Rg3 possesses anti-cancer properties. Colon Cancer Associated Transcript 1 (CCAT1) participates in the genesis, development, invasion and metastasis of colorectal cancer. In our study, we explored the effects of Rg3 on CRC cell line Caco-2 by regulating CCAT1. CRC tissue was obtained from hospital and Caco-2 cells were purchased. Caco-2 cells were treated with Rg3 and/or transfected with pc- CCAT1 or pcDNA3.1. The group without Rg3 treatment was treated as control. Cell viability, cell apoptosis, cell migration and invasion were detected by Cell Counting Kit-8 assay, flow cytometry and Transwell chamber migration/invasion assay, respectively. The expression of CyclinD1, apoptosis related proteins (p53, Bcl-2, Bax, pro-/Cleaved-Caspase-3), migration and invasion related proteins (MMP-9 and vimentin), and phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) related proteins (p/t-PI3K, p/t-AKT) were examined by western blot. The expression of CCAT1 was measured by quantitative real time RCR (qRT-PCR). Rg3 significantly decreased cell viability, migration and invasion, and promoted apoptosis. Meanwhile, the expression of Cyclin D1, matrix metalloproteinase (MMP)-9 and vimentin was downregulated. The expression of apoptosis-related proteins p53, Bax, and Cleaved-Caspase-3 were upregulated while Bcl-2 was downregulated by the treatment of Rg3 compared with control. Furthermore, CCAT1 was upregulated in CRC tissue and Rg3 negatively regulated CCAT1 expression. Transfection with pc-CCAT1 led to the opposite results as compared with transfection with pcDNA3.1 in Rg3 treated cells. In addition, Rg3 decreased the phosphorylation of PI3K and AKT. Ginsenoside Rg3 inhibits migration and invasion, and promotes apoptosis of Caco-2 cells by suppression expression of LncRNA CCAT1.


Impact of a preoperative evaluation on the outcomes of an arteriovenous fistula.
The aim of this study was to determine the possible predictors of primary arteriovenous fistula (AVF) failure and examine the impact of a preoperative evaluation on AVF outcomes. A total of 539 patients who underwent assessment for a suitable site for AVF creation by physical examination alone or additional duplex ultrasound were included in this study. Demographics, patient characteristics, and AVF outcomes were analyzed retrospectively. AVF creation was proposed in 469 patients (87.0%) according to physical examination alone (351 patients) or additional duplex ultrasound (118 patients); a prosthetic arteriovenous graft was initially placed in the remaining 70 patients (13.0%). Although the primary failure rate was significantly higher in patients assessed by duplex ultrasound (P = 0.001), ultrasound information changed the clinical plan, increasing AVF use for dialysis, in 92 of the 188 patients (48.9%) with an insufficient physical examination. Female sex and diabetes mellitus were risk factors significantly associated with primary AVF failure. Because of different inclusion criteria and a lack of adjustment for baseline differences, Kaplan-Meier survival analysis showed better AVF outcomes in patients assessed by physical examination alone; an insufficient physical examination was the only risk factor significantly associated with AVF outcomes. Routine use of duplex ultrasound is not necessary in chronic kidney disease patients with a satisfactory physical examination. Given that female gender and diabetes mellitus are significantly associated with primary AVF failure, duplex ultrasound could be of particular benefit in these subtypes of patients without a sufficient physical examination.


Prognostic value of beta1,6-branched oligosaccharides in human colorectal carcinoma.
Increase of beta1,6-branched oligosaccharides is possibly associated with tumor progression and lymph node metastasis. The aim of this study was to determine the prognostic value of beta1,6 branches in human colorectal carcinoma. Expression of beta1,6 branches was histochemically evaluated using the leukoagglutinating Phaseolus vulgaris lectin, PHA-L, in 92 clinically documented colorectal carcinomas, of which 31 had formed lymph node metastases. The follow-up time ranged between 4 and 14 years (median, 10.3 years). A PHA-L staining index (SI), taking into account staining intensity and its percentage of tumor cut surface area, was established. The carcinoma SI was highly associated with the disease-free survival (P = 0.004) and overall survival (P = 0.005). Patients with a carcinoma SI of >1, as compared to those with a SI of < or =1, were at significantly higher risk for tumor recurrence, with a shorter disease-free survival (hazard ratio = 2.59, P = 0.005) and significant higher risk of death with shorter overall survival (hazard ratio = 2.51, P = 0.007). The carcinoma SI was also associated with the presence of lymph node metastases. We conclude that PHA-L staining in human colorectal carcinoma sections provides an independent prognostic indicator for tumor recurrence and patient survival and is associated with the presence of lymph node metastases.