Phenotypic and molecular detection of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates from patients with burns in Tehran, Iran.
Health care-associated infections caused by metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa are a significant growing concern in patients with burns worldwide. The aims of this study were to determine the antibiotic susceptibility of and detect the presence of MBLs among P. aeruginosa isolates and assess their clonal relationship using enterobacterial repetitive intergenic consensus (ERIC)-PCR. Non-duplicated clinical isolates (160) of P. aeruginosa were collected from patients with burns at the Motahari Hospital in Tehran, Iran. All isolates were identified using standard laboratory methods and further characterized for antimicrobial susceptibility. Any carbapenem-resistant isolates were then examined for MBL production by the E-test and MBL-encoding genes were detected by PCR. The clonal relatedness of MBL-producing isolates was assessed by ERIC-PCR. For multidrug-resistant isolates, the highest rates of susceptibility were observed for colistin 160 (100%), polymyxin B 160 (100%), and ceftazidime 32 (20%). In total, 69 (43.7%) isolates were identified as MBL producers. Twenty-eight (17.5%) isolates were positive for the bla VIM-1 gene followed by the bla IMP-1 (15.6%) and bla SPM-1 (5.6%) genes. ERIC-PCR revealed three separate genotypes, where type A (76.8%) was the most prevalent, followed by B (20.3%), and then C (2.9%). Our present study found that the bla IMP-1 and bla VIM-1 genes were present at a significant frequency and also detected the bla SPM-1 gene in P. aeruginosa isolates for the first time, highlighting the need for establishing suitable infection control measures to successfully treat patients and prevent further spread of these resistant organisms among patients with burns.


Synthesis of Highly Conductive, Uniformly Silver-Coated Carbon Nanofibers by Electroless Deposition.
Noble-metal-coated carbon-based nanoparticles, when used as electrically conductive fillers, have the potential to provide excellent conductivity without the high weight and cost normally associated with metals such as silver and gold. To this effect, many attempts were made to deposit uniform metallic layers on core nanoparticles with an emphasis on silver for its high conductivity. The results so far were disheartening with the metal morphology being better described as a decoration than a coating with small effects on the electrical conductivity of the bulk particles. We tackled in this work the specific problem of electroless deposition of silver on carbon nanofibers (CNFs) with the investigation of every step of the process. We performed X-ray photoelectron spectroscopy (XPS), transmission and scanning electron microscopy (TEM, SEM), zeta potential, and electrical conductivity measurements to identify a repeatable, reliable set of parameters allowing for a uniform and fully connected silver deposition on the surface of the CNFs. The bulk particles' specific electrical conductivity (conductivity per unit mass) undergoes a more than 10-fold increase during the deposition, reaching 2500 S·cm2/g, which indicates that the added metal mass participates efficiently to the conduction network. The particles keep their high aspect ratio through the process, which enables a percolated conduction network at very low volume loadings in a composite. No byproducts are produced during the reaction so the particles do not have to be sorted or purified and can be used as produced after the short ∼15 min reaction time. The particles might be an interesting replacement to conventional fillers in isotropic conductive adhesives, as a conductive network is obtained at a much lower loading. They might also serve as electrically conductive fillers in composites where a high conductivity is needed, such as lightning strike protection systems, or as high surface area silver electrodes.


Is there any intersectoral coordination between health and education department at primary health center level?
One of the principles of primary health care is intersectoral co-ordination. A cross sectional study done at the primary health center revealed existence of unsatisfactory co-ordination between health and education department.


Bayesian sensitivity analysis for unmeasured confounding in observational studies.
We consider Bayesian sensitivity analysis for unmeasured confounding in observational studies where the association between a binary exposure, binary response, measured confounders and a single binary unmeasured confounder can be formulated using logistic regression models. A model for unmeasured confounding is presented along with a family of prior distributions that model beliefs about a possible unknown unmeasured confounder. Simulation from the posterior distribution is accomplished using Markov chain Monte Carlo. Because the model for unmeasured confounding is not identifiable, standard large-sample theory for Bayesian analysis is not applicable. Consequently, the impact of different choices of prior distributions on the coverage probability of credible intervals is unknown. Using simulations, we investigate the coverage probability when averaged with respect to various distributions over the parameter space. The results indicate that credible intervals will have approximately nominal coverage probability, on average, when the prior distribution used for sensitivity analysis approximates the sampling distribution of model parameters in a hypothetical sequence of observational studies. We motivate the method in a study of the effectiveness of beta blocker therapy for treatment of heart failure.


Allogeneic adipose-derived stem cell transplantation on knee osteoarthritis rats and its effect on MMP-13 and DDR2.
This study investigated the efficacy of transplantation of allogeneic adipose-derived stem cells (ADMSCs) in rats with knee osteoarthritis (KOA) and the effect on the expression of matrix metalloproteinase 13 (MMP-13) and discoid domain receptor 2 (DDR2). In total, sixty rats were randomly selected. Eleven rats were selected as the blank group. Forty-four rat KOA models were established, and the remaining 5 rats were used for stem cell extraction. The rats were randomly divided into two groups, and the transplantation group was treated with ADMSCs transplantation. The KOA group was intragastrically administered with saline. The expressions of MMP-13 mRNA and DDR2 in rats were detected by RT-qPCR and immunohistochemistry. Correlation analysis was performed in MMP-13 mRNA and DDR2 expression levels in the KOA rats. After treatment, the indexes of Lequesne MG knee joints, MMP-13 mRNA and DDR2 in the transplanted rats were significantly lower than those in the KOA group (P<0.05). In the KOA rats, MMP-13 mRNA and DDR2 was positively correlated (r=0.830, P<0.001). Therefore, the transplantation of ADMSCs has a significant effect on the KOA rats, which can effectively improve the knee joint function of KOA rats and reduce the expression of MMP-13 mRNA and DDR2 in rats, and it is worthy of clinical promotion.


Optical sensors based on III-nitride photodetectors for flame sensing and combustion monitoring.
Combustion control requires visible photodetectors to sense the CH* CL emission at 430 nm that combined with a visible-blind UV photodetector allows us to obtain the OH*/CH* ratio. UV-visible P-InGaN/GaN multiple quantum well-N photodiodes with 15-18 mm2 areas were fabricated to conduct OH* (308 nm) and CH* CL detection without external filters. Bandpass detectors at 230-390 nm and 360-450 nm presented linear responses over five decades and rejection ratios >10(3) at 430 and 308 nm, respectively. A full optical sensor system was built and detectors operated at 120 degrees C in a combustion chamber, showing linear responses within the dynamic range, maximum signal-to-noise ratios of 103 and response times of <1 s. An exponential association dependence between the optical OH*/CH* CL signals and the gas/air ratios was found.


Liquid-chromatographic measurement of amino acids in biological samples after formation of phenylthiohydantoin derivatives.
In this method for measuring amino acids in urine, serum, and tissue, the amino acids to be assayed and the internal standard, L-norleucine, are converted to phenylthiohydantoins , isolated by organic solvent extraction, separated by reversed-phase "high-pressure" liquid chromatography, and detected by ultraviolet absorbance. The analytes are identified by retention times and quantified by comparing peak heights with that of the internal standard. The peak-height ratios vary linearly with concentrations of 50 to 500 mg/L, corresponding to the concentration range usually found in biological samples. Detection limits are 5 to 20 mg/L. Inter- and intra-assay precision (CV) varies between 1 and 26%. Average analytical recoveries range between 67 and 100%.


The impact of pandemic-related social distancing regulations on exercise performance-Objective data and training recommendations to mitigate losses in physical fitness.
In the context of the COVID-19 pandemic in Germany, governmental restrictions led to the closure of sports facilities for several months. To date, only subjective and fitness-tracking related data on physical activity during the pandemic are available. Using data of a chip-controlled fitness circuit, training data as a measure of physical performance before and after the lockdown during the first wave of the COVID-19 pandemic will show the impact of the training interruption on exercise performance in middle-aged and older adults. The re-training data are analyzed, to extract practical recommendations. Objective training data of 17,450 participants [11,097 middle-aged (45-64 yrs), 6,353 older (≥65 yrs)] were exported from chip-controlled milon® fitness circuit systems before and after the first COVID-19 related lockdown in Germany. The change in the product of training weight (sum of lifting and lowering the training weight) and repetitions on the leg extension resistance exercise device (leg score) between the last three training sessions before the lockdown and the first ten training sessions after individual training resumption as well as the last training session before the second lockdown in October 2020 was analyzed. Participants who trained with high intensity before the lockdown, experienced deleterious effects of the training interruption (middle-aged group: -218 kg, older group: ~-230.8 kg; p < 0.001 for change in leg score from to post-lockdown) with no age effect. Participants training with a leg score of more than 3,000 kg did not resume their leg score until the second lockdown. The interruption of training in a fitness circuit with combined resistance and endurance training due to the lockdown affected mainly those participants who trained at high intensity. Apparently, high-intensity training could not be compensated by home-based training or outdoor activities. Concepts for high-intensity resistance training during closure of sports facilities are needed to be prepared for future periods of high incidence rates of infectious diseases, while especially vulnerable people feel uncomfortable to visit sports facilities. Identifier, DRKS00022433.


Traits of hospice nurses compared with those who work in traditional settings.
Compared 36 hospice nurses with 35 nurses who were working in traditional settings. Data from a battery of five tests ( Templer Death Anxiety Scale, Purpose in Life, Shneidman "You and Death" Questionnaire, Myers- Briggs , Cattell 16PF) revealed the hospice nurses to be significantly more assertive, imaginative, forthright , free-thinking and independent than their colleagues, who scored lower than the norms. The nurses in traditional settings exhibited a stronger preference than both hospice nurses and norms for the practical and no-nonsense in their approach to life. They were also more conventional and comfortable with structure. These data suggest a useful basis for hospice staff selection procedures as well as further study of the hospice as a setting evocative of autonomous professional nursing practice.


[Personnel and material conditions of the Hungarian intensive care units dealing with organ donation].
At the end of 2016, the number of patients on the domestic transplant waiting list was twice as much as the number of the organ transplantations accomplished that year. The institutional prerequisites for functional organ donation programs are the sufficient number of personnel and the adequate material conditions to be provided in relation to the needs. The goal of the current study was to evaluate the professional environment in Hungary. The Organ Coordination Office at the Hungarian National Blood Transfusion Service compiled a questionnaire survey on the personnel and material conditions of the intensive care units (ICUs) in Hungary in regards to organ donations. The survey applied an online questionnaire including 43 questions. In addition to the number of beds and employees, we investigated the tools needed for the legal and the medical diagnosis of brain death as well as the accessibility of examinations on the donor information form. The data collection spanned from 12 December 2016 to 30 June 2017. 59 intensive care units completed the questionnaire; the investigation involved 640 hospital beds, 816 physicians and 1252 nurses. In the daytime shift, 0.25 doctors and 0.41 nurses work on a patient bed at an average, while in the night shift, the figures are 0.11 and 0.33, respectively. 51.7% of the doctors are registered to access the National Non-Donor Registry, and brain death diagnosis committee is available in 83% of the hospitals. Among the medical imaging methods (cranial, abdominal-thoracic), CT scan in 71-73%, abdominal ultrasound in 75%, transthoracic echocardiograpy (TTE) in 37%, transoesophageal echocardiography (TEE) in 4%, bronchoscopy in 49%, coronarography in 19% are non-stop available, with instant interpretation in 75% of the cases. Transcranial Doppler (TCD) in 30%, four-vessel angiography in 45% and SPECT in 14% of the cases are available. More than 90% of the laboratory examinations on the donor information form are available 24 hours a day. The number of doctors and nurses did not change compared to our 2008 survey (0.18 doctors, 0.37 nurses/ICU beds in 2008), but the care of potential donors needs more resources and time. The standby availability of personnel and material conditions is a prerequisite for organ donation programs in order to save lives. Orv Hetil. 2018; 159(33): 1360-1367.


[Chemical Constituents from Leaves of "Chuju" Chrysanthemum morifolium and Their Antioxidant Activities in vitro].
To study the chemical constituents from the leaves of "Chuju" Chrysanthemum morifolium. All compounds were separated and purified by column chromatography over silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified by spectral methods including 1H-NMR and 13C-NMR. 21 compounds were isolated and identified as octa-cosyl alcohol (1), β-sitosterol (2), lupeol (3), α-amyrin (4), daucosterol (5), ineupatorolide B (6), syringin (7), chlorogenic acid (8), petasiphenol (9), physcion (10), acacetin (11), eupatilin (12), quercetin (13), diosmetin (14), luteolin (15), apigenin (16), apigenin- 7-O-β-D-glucopyranoside (17), quercetin-3-O-β-D-glucopyranoside (18), luteolin-7-O-β-D-gluco pyranoside (19), apigenin-7-O-β-D- neospheroside (20), and acacetin-7-O-β-D-glucoside (21). Compounds 1-12, 18 and 20 are isolated from this plant for the first time. Compounds 10, 13, 14, 15 and 16 have shown strong antioxidant activities by DPPH · scavenging activity better than Vit C.


Thin film block copolymer self-assembly for nanophotonics.
The nanophotonic engineering of light-matter interactions has profoundly changed research behind the design and fabrication of optical materials and devices. Metasurfaces-arrays of subwavelength nanostructures that interact resonantly with electromagnetic radiation-have emerged as an integral nanophotonic platform for a new generation of ultrathin lenses, displays, polarizers and other devices. Their success hinges on advances in lithography and nanofabrication in recent decades. While existing nanolithography techniques are suitable for basic research and prototyping, issues of cost, throughput, scalability, and substrate compatibility may preclude their use for many metasurface applications. Patterning via spontaneous self-assembly of block copolymer thin films offers an enticing alternative for nanophotonic manufacturing that is rapid, inexpensive, and applicable to large areas and diverse substrates. This review discusses the advantages and disadvantages of block copolymer-based nanopatterning and highlights recent progress in their use for broadband antireflection, surface enhanced Raman spectroscopy, and other nanophotonic applications. Recent advances in diversification of self-assembled block copolymer nanopatterns and improved processes for enhanced scalability of self-assembled nanopatterning using block copolymers are also discussed, with a spotlight on directions for future research that would enable a wider array of nanophotonic applications.


Prehospital Trauma Care in Singapore.
Prehospital emergency care in Singapore has taken shape over almost a century. What began as a hospital-based ambulance service intended to ferry medical cases was later complemented by an ambulance service under the Singapore Fire Brigade to transport trauma cases. The two ambulance services would later combine and come under the Singapore Civil Defence Force. The development of prehospital care systems in island city-state Singapore faces unique challenges as a result of its land area and population density. This article defines aspects of prehospital trauma care in Singapore. It outlines key historical milestones and current initiatives in service, training, and research. It makes propositions for the future direction of trauma care in Singapore. The progress Singapore has made given her circumstances may serve as lessons for the future development of prehospital trauma systems in similar environments. Key words: Singapore; trauma; prehospital emergency care; emergency medical services.


Interplay between alveolar epithelial and dendritic cells and Mycobacterium tuberculosis.
The innate response plays a crucial role in the protection against tuberculosis development. Moreover, the initial steps that drive the host-pathogen interaction following Mycobacterium tuberculosis infection are critical for the development of adaptive immune response. As alveolar Mϕs, airway epithelial cells, and dendritic cells can sense the presence of M. tuberculosis and are the first infected cells. These cells secrete mediators, which generate inflammatory signals that drive the differentiation and activation of the T lymphocytes necessary to clear the infection. Throughout this review article, we addressed the interaction between epithelial cells and M. tuberculosis, as well as the interaction between dendritic cells and M. tuberculosis. The understanding of the mechanisms that modulate those interactions is critical to have a complete view of the onset of an infection and may be useful for the development of dendritic cell-based vaccine or immunotherapies.


[PET using 11C-methionine in recognition of pseudoprogression in cerebral glioma after combined treatment].
The purpose of the study was to evaluate the value of PET using 11C-methionine (PET-Met) for distinction between true glioma progression and pseudoprogression (PsPr). 72 patients with treated cerebral glioma investigated by PET-Met were identified from prospective database. Entry criteria included new or progressive MR imaging enhancing lesions within first 6 months after irradiation and definite final diagnosis on the basis of the pathological study (n=17) or clinical-radiological follow-up on an average 16 months. PET examinations were assessed by visual inspection and calculating 11C-methionine uptake index (UI). Results. Pseudoprogression was defined as early radiological progression with subsequent regress or stabilization, without salvage therapy. 42 patients were considered to exhibit PsPr and 30 patients had true glioma progression. In PsPr group PET scans were either negative (n=6) or slightly increased tracer uptake (UI range 1.2-2.14) was seen in the site of contrast-enhanced lesion. The UI was 1.48±0.39 (mean±SD). In comparison with pretreatment PET 15 patients showed decrease 11C-methionine uptake on an average by 26%. In recurrence group PET-Met showed abnormal high focal 11C-methionine uptake in the lesion. The UI was 2.54±0.84 (range 1.54-5.4). An UI threshold value of greater than 1.9 optimized differentiation between glioma progression and PsPr with sensitivity of 83.5% and specificity of 97.0%. Conclusion. Metabolic characteristics of PsPr included negative tracer accumulation or slightly increased 11C-methionine uptake in the contrast-enhancing lesion with UI less than 1.9.


p-Wave superfluidity by spin-nematic Fermi surface deformation.
We study attractively interacting fermions on a square lattice with dispersion relations exhibiting strong spin-dependent anisotropy. The resulting Fermi surface mismatch suppresses the s-wave BCS-type instability, clearing the way for unconventional types of order. Unbiased sampling of the Feynman diagrammatic series using diagrammatic Monte Carlo methods reveals a rich phase diagram in the regime of intermediate coupling strength. Instead of a proposed Cooper-pair Bose metal phase [A. E. Feiguin and M. P. A. Fisher, Phys. Rev. Lett. 103, 025303 (2009)], we find an incommensurate density wave at strong anisotropy and two different p-wave superfluid states with unconventional symmetry at intermediate anisotropy.


The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.
The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis. A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, α and β diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis. Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the α and β diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection. The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.


Abdominal wall endometriosis: a diagnostic dilemma for surgeons.
To report 3 cases of endometriosis of the abdominal wall, a disease which is unfamiliar to general surgeons because of the potential pitfalls in its diagnosis. Three patients were referred to our general surgery clinic for abdominal masses. Incisional hernia and an abdominal mass were initially suspected in 2 patients, while a preoperative diagnosis of a rectus abdominis hematoma was made in the third because she had no history of previous surgery. Pain was a remarkable complaint in only one of the present cases. Abdominal wall endometriosis was diagnosed only upon histological examination postoperatively. In all cases, ultrasonography revealed hypoechogenic masses, and computed tomography showed that these masses had spiculations, and macroscopic views of the resected masses revealed well-demarcated margins without peritoneal involvement. All patients were treated with wide radical resections followed by polytetrafluoroethylene patch grafting. They were discharged from hospital on either the 2nd or the 3rd postoperative day uneventfully, and during follow-up there were no signs of pelvic endometriosis, as confirmed by ultrasonography, CA 125 measurement, gynecological consultation and examination. Since the diagnosis of scar endometrioma is rarely established prior to surgery, endometriosis should be included in the differential diagnosis of masses on the abdominal wall.


Simultaneously estimating food web connectance and structure with uncertainty.
Food web models explain and predict the trophic interactions in a food web, and they can infer missing interactions among the organisms. The allometric diet breadth model (ADBM) is a food web model based on the foraging theory. In the ADBM, the foraging parameters are allometrically scaled to body sizes of predators and prey. In Petchey et al. (Proceedings of the National Academy of Sciences, 2008; 105: 4191), the parameterization of the ADBM had two limitations: (a) the model parameters were point estimates and (b) food web connectance was not estimated.The novelty of our current approach is: (a) We consider multiple predictions from the ADBM by parameterizing it with approximate Bayesian computation, to estimate parameter distributions and not point estimates. (b) Connectance emerges from the parameterization, by measuring model fit using the true skill statistic, which takes into account prediction of both the presences and absences of links.We fit the ADBM using approximate Bayesian computation to 12 observed food webs from a wide variety of ecosystems. Estimated connectance was consistently greater than previously found. In some of the food webs, considerable variation in estimated parameter distributions occurred and resulted in considerable variation (i.e., uncertainty) in predicted food web structure.These results lend weight to the possibility that the observed food web data is missing some trophic links that do actually occur. It also seems likely that the ADBM likely predicts some links that do not exist. The latter could be addressed by accounting in the ADBM for additional traits other than body size. Further work could also address the significance of uncertainty in parameter estimates for predicted food web responses to environmental change.


Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks.
Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed "kinetic insulation." In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity.


Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy.
Recent data derived primarily from studies in animal models suggest that fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis. We, therefore, hypothesized that enhanced CX3CL1/CX3CR1 expression may promote atherogenesis in patients with coronary artery disease (CAD). We examined the plasma levels of CX3CL1 and CX3CR1 expression in peripheral blood mononuclear cells (PBMC) in various CAD populations (30 patients with previous myocardial infarction, 40 patients with stable angina, 40 patients with unstable angina, and a total of 35 controls) and used various experimental approaches to characterize CX3CL1-mediated leukocyte responses. We found that the plasma levels of CX3CL1 are greatly increased in CAD, particularly in unstable disease. The parallel increase of CX3CR1 expression in PBMC was predominantly attributable to an expansion of the (CX3CR1+)(CD3+)(CD8+) T cell subset and was associated with enhanced chemotactic, adhesive, and inflammatory responses to CX3CL1. Statin therapy for 6 months reduced the expression of CX3CL1 and CX3CR1, reaching statistical significance for both parameters only during aggressive (atorvastatin, 80 mg qd) but not conventional (simvastatin, 20 mg qd) therapy. Consequently, the functional responses of the PBMC to CX3CL1 including migration, adhesion, and secretion of interleukin-8 were attenuated by the treatments. Our results suggest that the CX3CL1/CX3CR1 dyad may contribute to atherogenesis and plaque destabilization in human CAD.


Morel-Lavallée syndrome of the tibia.
Morel-Lavallée syndrome of the tibia is a rarely published entity which needs special attention in the treatment of the degloving injury conjoined with tibial fracture. The authors present the case of a radiologically easily manageable tibial fracture complicated by soft tissue damage. The authors discuss the pertinent literature, the pitfalls and controversies of the treatment and the authors would like to offer our suggestions for minimising the complications.


Weak but Critical Links between Primary Somatosensory Centers and Motor Cortex during Movement.
Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging (fMRI) study in 21 healthy subjects under three different conditions: (1) movement of right ankle alone; (2) movement and simultaneous stimulation of the agonist muscle; or (3) movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that: (1) the second condition evokes the strongest and most widespread brain activations (5147 vs. 4419 and 2320 activated voxels); and (2) this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most "silent" links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex (M1). Significant statistical differences were found when the strength values of the right cerebellum (P < 0.001) or the left thalamus (P = 0.006) were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.


The worst injury predicts mortality outcome the best: rethinking the role of multiple injuries in trauma outcome scoring.
The prediction of outcome after injury must incorporate measures of injury severity, but there is no consensus on how many injuries should be used in calculating these measures. Initially, the single worst injury was used to predict outcome, but the introduction of the Injury Severity Score allowed up to three injuries to contribute to outcome prediction. Subsequently, other outcome prediction approaches used many (New Injury Severity Score [NISS]) or all (ICISS and Trauma Registry Abbreviated Injury Scale Score [TRAIS], which use International Classification of Diseases, Ninth Revision [ICD-9] and Abbreviated Injury Scale [AIS] survival risk ratios [SRRs], respectively) of a patient's injuries. The ability of only the most severe injury in predicting mortality has never been studied. Our objective was to determine the ability of a patient's worst injury to predict mortality. A 10-fold cross-validation design was used to compute six scores for each of 160,208 patients from a large trauma database (the National Trauma Data Bank [NTDB]). The scores were ICISS, TRAIS, ICISS1 (only a patient's worst ICD-9 SRR), TRAIS1 (only a patient's worst AIS SRR), NISS (sum of squares of worst three AIS severity measures), and MAXAIS (worst AIS severity measure). Discrimination was assessed using the area under the receiver operating characteristic curve. Logistic regression R2 gauged the proportion of variance each score explained. The Akaike information criterion, a deviance statistic (lower is better), assessed model fit. The receiver operating characteristic curve, R2, and Akaike information criterion statistics (NC_ICISS and NC_ICDSRR1 represents scores derived from the original North Carolina Hospital Discharge Database SRRs) are summarized in tabular form in the Results section. Regardless of scoring type (ICD/AIS SRRs or AIS severity), a patient's worst injury discriminates survival better, fits better, and explains more variance than currently used multiple injury scores.


Structure of nuclear ribonucleoprotein: identification of proteins in contact with poly(A)+ heterogeneous nuclear RNA in living HeLa cells.
The processing of heterogeneous nuclear RNA into messenger RNA takes place in special nuclear ribonucleoprotein particles known as hnRNP. We report here the identification of proteins tightly complexed with poly(A)+ hnRNA in intact HeLa cells, as revealed by a novel in situ RNA-protein cross-linking technique. The set of cross-linked proteins includes the A, B, and C "core" hnRNP proteins, as well as the greater than 42,000 mol wt species previously identified in noncross-linked hnRNP. These proteins are shown to be cross-linked by virtue of remaining bound to the poly(A)+ hnRNA in the presence of 0.5% sodium dodecyl sulfate, 0.5 M NaCl, and 60% formamide, during subsequent oligo(dT)-cellulose chromatography, and in isopycnic banding in Cs2SO4 density gradients. These results establish that poly(A)+ hnRNA is in direct contact with a moderately complex set of nuclear proteins in vivo. This not only eliminates earlier models of hnRNP structure that were based upon the concept of a single protein component but also suggests that these proteins actively participate in modulating hnRNA structure and processing in the cell.


Mode of action of microbial bioactive metabolites.
Pathogenic microorganisms can be suppressed by cell wall destruction. Biosynthesis of peptidoglycans forming bacterial cell wall is interrupted by glycopeptides which inhibit polymerization of a disaccharide formed by N-acetylglucosamine and N-acetylmuramic acid, beta-lactams and their derivatives inhibit peptidoglycan cross-linking. Antibiotics inhibiting protein synthesis bind to different sites on the rRNA and interfere with the formation of the polypeptide chain. Tumor cells resistant to chemotherapeutic drugs overproduce proteins transporting the drugs out of cells; these proteins eliminate substances which inhibit transcription of transport proteins. Some antitumor drugs (anthracyclines, fluoroquinolones, acridines etc.) act at topoisomerases which irreversibly bind to DNA and inhibit DNA synthesis. Immunosuppressants affect various components of the immune system such as T-helper, T-effector cell function, antigen presentation and B-cell function. Antiparasitics--avermectins--bind to a receptor of this Gab-gated chlorine channel in the nerve fiber of nematodes and anthropodes, increasing the permeability of the membrane for chloride ions; the increased transport of chloride ions into the cell causes the death of the parasite. Ionophores dissolve in phospholipid bilayers and enormously increase their ionic permeability. Respiration inhibitors block the transport of electrons at several places of the respiratory chain. Rifamycin binds to the beta subunit of bacterial RNA polymerase, thereby blocking mRNA synthesis. Antiviral compounds inhibit the transcription of DNA by several mechnisms or by inhibition of viral entry into host cells.


Difference in protective effects of GIP and GLP-1 on endothelial cells according to cyclic adenosine monophosphate response.
Receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are present in vascular endothelial cells. Previous studies investigating euglycemic status have demonstrated that GIP is directly involved in the physiology of blood vessels by controlling the blood flow rate of portal veins and that GLP-1 has a protective effect on blood vessels by acting on endothelial cells. However, to the best of our knowledge, the effects of GIP and GLP-1 on endothelial cells in patients with hyperglycemia remain unknown. Therefore, the present study investigated whether the effect of the incretin hormones GLP-1 and GIP differed with regards to the reversal of endothelial cell dysfunction caused by hyperglycemia. The production of nitric oxide (NO) was measured using the Griess reagent system kit and the expression of cyclic adenosine monophosphate (cAMP) in the cell was measured at a wavelength of 405 nm with the ELISA reader using the cyclic AMP EIA kit. Exposure of human umbilical vein endothelial cells (HUVEC) to a high glucose concentration decreased NO and endothelial nitric oxide synthase (eNOS) levels but increased inducible NOS (iNOS) levels. However, when HUVECs were pretreated with GLP-1, a reduction of iNOS expression was observed and the expression of eNOS and NO were increased, as opposed to pretreatment with GIP. The results differed according to the response of cAMP, the second messenger of incretin hormones: The GIP pretreatment group did not exhibit an increase in cAMP levels while the GLP-1 pretreatment group did. The results of the present study provide evidence that GLP-1, but not GIP, has a protective effect on endothelial function associated with cardiovascular disease, as it is associated with increased eNOS expression and the levels of NO. This effect may be due to an increase in the cAMP concentration during hyperglycemic events.


The association between community social vulnerability and prescription opioid availability with individual opioid overdose.
This study aims to assess the association of community social vulnerability and community prescription opioid availability with individual non-fatal or fatal opioid overdose. We identified patients 12 years of age or older from the Oregon All Payer Claims database (APCD) linked to other public health datasets. Community-level characteristics were captured in an exposure period (EP) (1/1/2018-12/31/2018) and included: census tract-level social vulnerability domains (socio-economic status, household composition, racial and ethnic minority status, and housing type and transportation), census tract-level prescriptions and community-level opioid use disorder (OUD) diagnoses per 100 capita binned into quartiles or quintiles. We employed Cox models to estimate the risk of fatal and non-fatal opioid overdoses events in the 12 months following the EP. We identified 1,548,252 individuals. Patients were mostly female (54%), White (61%), commercially insured (54%), and lived in metropolitan areas (81%). Of the total sample, 2485 (0.2%) experienced a non-fatal opioid overdose and 297 died of opioid overdose. There was higher hazard for non-fatal overdose in communities with greater OUD per 100 capita. We also found higher non-fatal and fatal hazards for opioid overdose among patients in communities with higher housing type and transportation-related vulnerability compared to the lowest quintile. Conversely, patients were at less risk of opioid overdose when living in communities with greater prevalence of the young or the elderly, the disabled, single parent families or low English proficiency. These findings underscore the importance of the environmental context when considering public health policies to reduce opioid harms.


[Diabetes mellitus and the digestive tract].
The author discusses in the submitted paper the important subject of manifestations of diabetes in the digestive tract--oesophagus, stomach, small and large intestine. Autonomous neuropathy, in particular a reduced tonus of the vagus, leads to a number of functional disorders which can produce diabetic dysphagia, gastroparesis, diarrhoea and constipation. The reduced tonus of the vagus, along with other factors, may lead to atrophy of the gastric mucosa and reduced gastric secretion. This explains the higher incidence of atrophic gastritis and other complications in diabetic patients. The author discusses also basic clinical aspects of these disorders and outlines therapeutic procedures.


Human neutrophil development and functionality are enabled in a humanized mouse model.
Mice with a functional human immune system serve as an invaluable tool to study the development and function of the human immune system in vivo. A major technological limitation of all current humanized mouse models is the lack of mature and functional human neutrophils in circulation and tissues. To overcome this, we generated a humanized mouse model named MISTRGGR, in which the mouse granulocyte colony-stimulating factor (G-CSF) was replaced with human G-CSF and the mouse G-CSF receptor gene was deleted in existing MISTRG mice. By targeting the G-CSF cytokine-receptor axis, we dramatically improved the reconstitution of mature circulating and tissue-infiltrating human neutrophils in MISTRGGR mice. Moreover, these functional human neutrophils in MISTRGGR are recruited upon inflammatory and infectious challenges and help reduce bacterial burden. MISTRGGR mice represent a unique mouse model that finally permits the study of human neutrophils in health and disease.


Drosera-Inspired Dual-Actuating Double-Layer Hydrogel Actuator.
Drosera is a small insectivorous plant whose antennae can fold up, encircle, and prey. The rapid movement of the antennae is achieved by the synergistic effect of a double-layer structure with the antennae contracts on the front and expands on the back. In this work, a drosera-inspired dual-actuating double-layer hydrogel actuator is proposed, in which the temperature-responsive poly(N, N-diethyl acrylamide) (PDEAAm) layer acts as the main actuation layer and a moisture-responsive poly(acrylamide) (PAAm) layer acts as the auxiliary actuation layer. In a water environment with low temperature, both the PAAm and PDEAAm layers absorb water and expand with a swelling property. When the temperature exceeds the lower critical solution temperature of PDEAAm, the PDEAAm layer undergoes a hydrophilic-hydrophobic transition and shrinks rapidly. Therefore, the synergistic effect of the double-layer hydrogel enables the double-layer hydrogel to achieve a large bending angle at high temperature. In addition, when designing and fabricating shape-patterned double-layer hydrogels, complex shape changes can be achieved. Due to the physical and chemical properties, the actuator can be used to grab, transport, and release objects. This drosera-inspired double-layer hydrogel actuator has high practical value, which may provide new insights for the design and manufacture of artificial intelligence materials.


Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors.
Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h. The expression of ErbB receptors and NRG-1 in HCMECs was measured by western blot analysis and the secretion of NRG-1 in HCMECs was determined by ELISA. The results demonstrated that ErbB2, ErbB3 and ErbB4 were expressed in HCMECs and that ErbB2 expression levels were notably higher than those of ErbB3 and ErbB4. Under normal culture conditions the expression and secretion of NRG-1 was significantly increased in HCMECs treated with VEGF or Ang-1 (P<0.05), however levels significantly decreased in HCMECs treated with Ang-2 (P<0.05). Under Hypo/SD conditions the expression and secretion of NRG-1 significantly increased (P<0.05) and VEGF or Ang-1 treatment significantly increased these effects further (P<0.05). Conversely Ang-2 treatment significantly decreased these effects (P<0.05). The expression and release of NRG-1 were significantly increased in HCMECs with VEGF or Ang-1 treatment (P<0.05), which suggests that VEGF and Ang-1 may regulate myocardial angiogenesis and survival via the NRG-1/ErbB signaling pathway.


The evolving roles of radiolabeled quinones as small molecular probes in necrotic imaging.
Necrosis plays vital roles in living organisms which is related closely with various diseases. Non-invasively necrotic imaging can be of great values in clinical decision-making, evaluation of individualized treatment responses, and prediction of patient prognosis. This narrative review will demonstrate how the evolution of quinones for necrotic imaging has been promoted by searching for their active centers. In this review, we summarized the recent developments of various quinones with the continuous simplified π-conjugated cores in necrotic imaging and speculated their possible molecular mechanisms might be attributed to their intercalations with exposed DNA in necrotic tissues. We discussed their clinical challenges of necrotic imaging with quinones and their future translation studies deserved to be explored in personalized patient treatment.


Atomic domain magnetic nanoalloys: interplay between molecular structure and temperature dependent magnetic and dielectric properties in manganese doped tin clusters.
We present extensive temperature dependent (16-70 K) magnetic and electric molecular beam deflection measurements on neutral manganese doped tin clusters Mn/SnN (N = 9-18). Cluster geometries are identified by comparison of electric deflection profiles and quantum chemical data obtained from DFT calculations. Most clusters adopt endohedral cage structures and all clusters exhibit non-vanishing magnetic dipole moments. In the high temperature regime all species show exclusively high field seeking magnetic response and the magnetic dipole moments are extracted from the shift of the molecular beam. At low nozzle temperatures, some of the clusters show considerably broadened beam profiles due to non-uniform deflection in the magnetic field. The results reflect the influence of the chemical environment on the magnetic properties of the transition metal in atomic domain magnetic nanoalloys. Different ground state spin multiplicities and coupling of rotational and vibrational degrees of freedom with the spin angular momentum of isolated clusters of different size apparently cause these variations of spin orientation. This is discussed by taking electronic and molecular structure data into account.


Candidate genes for domestication and resistance to cold climate according to whole genome sequencing data of Russian cattle and sheep breeds.
It is known that different species of animals, when living in the same environmental conditions, can form similar phenotypes. The study of the convergent evolution of several species under the influence of the same environmental factor makes it possible to identify common mechanisms of genetic adaptation. Local cattle and sheep breeds have been formed over thousands of years under the influence of domestication, as well as selection aimed at adaptation to the local environment and meeting human needs. Previously, we identified a number of candidate genes in genome regions potentially selected during domestication and adaptation to the climatic conditions of Russia, in local breeds of cattle and sheep using whole genome genotyping data. However, these data are of low resolution and do not reveal most nucleotide substitutions. The aim of the work was to create, using the whole genome sequencing data, a list of genes associated with domestication, selection and adaptation in Russian cattle and sheep breeds, as well as to identify candidate genes and metabolic pathways for selection for cold adaptation. We used our original data on the search for signatures of selection in the genomes of Russian cattle (Yakut, Kholmogory, Buryat, Wagyu) and sheep (Baikal, Tuva) breeds. We used the HapFLK, DCMS, FST and PBS methods to identify DNA regions with signatures of selection. The number of candidate genes in potentially selective regions was 946 in cattle and 151 in sheep. We showed that the studied Russian cattle and sheep breeds have at least 10 genes in common, apparently involved in the processes of adaptation/selection, including adaptation to a cold climate, including the ASTN2, PM20D1, TMEM176A, and GLIS1 genes. Based on the intersection with the list of selected genes in at least two Arctic/Antarctic mammal species, 20 and 8 genes, have been identified in cattle and sheep, respectively, that are potentially involved in cold adaptation. Among them, the most promising for further research are the ASPH, NCKAP5L, SERPINF1, and SND1 genes. Gene ontology analysis indicated the existence of possible common biochemical pathways for adaptation to cold in domestic and wild mammals associated with cytoskeleton disassembly and apoptosis.


Cutaneous syncytial myoepithelioma: A recently described neoplasm which may mimic nevoid melanoma and epithelioid sarcoma.
Cutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well-circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan-keratin or p63. Break-apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.


ELAV inhibits 3'-end processing to promote neural splicing of ewg pre-mRNA.
The embryonic lethal abnormal visual system (ELAV) is a gene-specific regulator of alternative pre-mRNA processing in neurons of Drosophila. Here we define a functional in vivo binding site for ELAV in neurons through the development of a reporter gene system in transgenic animals in combination with in vitro binding assays. ELAV binds to erect wing (ewg) RNA 3' of a polyadenylation site in the terminal intron 6. At this polyadenylation site, ELAV inhibits 3'-end processing in vitro in a dose-dependent and sequence-specific manner, and ELAV binding is necessary in vivo to promote splicing of ewg intron 6. Further, the AAUAAA poly(A) complex recognition sequence, together with ELAV, is required to regulate neural 3' splice site choice in vivo. In addition, the use of segmentally labeled RNA substrates in UV cross-linking assays suggest that ELAV does not inhibit or redirect binding of cleavage factor dCstF64 at the regulated polyadenylation site on ewg RNA. These data indicate that binding of 3'-end processing factors, together with ELAV, can regulate alternative splicing.


Kininogenase activity in rat uterus homogenates.
A synthetic peptide substrate for tissue kallikreins was hydrolysed by uterus homogenates. These also released kinins when incubated with dog kininogen. By using high pressure liquid chromatography in combination with a radioimmunoassay for kinins, the peptides released were identified as bradykinin and kallidin. Plasma kallikrein and trypsin released bradykinin from dog kininogen and hog pancreas kallikrein released kallidin from this substrate. This suggests that a tissue kallikrein and also a trypsin-like enzyme or perhaps plasma kallikrein are present in rat uterus.


Drinking and occupational status in New Zealand men.
The self-reported alcohol consumption of various occupational groups in New Zealand is examined. A sample of 10,000, representative of the general adult population, was questioned in 1978-1979. Only data on men (N = 5000) are considered in the present study. Various occupations and groups of occupations are ranked on several variables of frequency and quantity of drinking. The interrelationships of these variables and the working conditions related to them are discussed. There is an association between drinking pattern and general social class, but 61% of the specific occupational groups form a cluster in the range of 25-60 ml of absolute alcohol consumed on one or two occasions per week. The extreme positions on drinking variables of specific occupational groups is examined in terms of job characteristics. Most of the correlations are very low; drinking at work is the highest. The relationships can best be described in terms of the social class of the occupational groups and the frequency vs quantity dichotomy. The distribution of the social classes in terms of drinking intensity is discussed. Employment in the lower classes is related to lower frequency and higher quantity of drinking, and higher cirrhosis mortality. Overall, social class appears to be a more important indicator than occupational group or drinking pattern.


Solitary Head and Neck Cysticercosis: A Series of Rare Cases.
Cysticercosis is a disease which is caused by the infestation of the larvae Taenia solium, with humans acting as an intermediate host instead of a definitive host. Head and neck involvement including maxillofacial and oral involvement of cysticercosis is quite rare. We report a series of rare cases of cysticercosis of the head and neck region encountered in a tertiary hospital in Northern India with a brief review of literature and its diagnosis and management. The patients had undergone ultrasonography, FNAC and CT scan. All the cases were treated by Oral Albendazole tablets. The period of study was from August 2014 to August 2015. FNAC proved to be a highly effective way of diagnosis corroborated by imaging evidence. Treatment with albendazole was curative in all the cases. Cytopathology has emerged as an excellent diagnostic modality for cysticercosis. Medical treatment with antihelminthics produces excellent results, as illustrated in our case, and can eliminate the need of surgery.


Automated evaluation of hip axis length for predicting hip fracture.
The hip axis length has been shown in previous studies to be predictive of hip fracture independent of age and femoral bone density. The first studies of hip axis length were performed by manual measurement of dual x-ray absorptiometry (DXA) scan printouts. In this study, an automated analysis procedure is defined using software tools provided by the DXA manufacturer. Manual and automatic hip axis length measurements in 198 women were highly correlated (r = 0.98). Because of scaling factors of the printout, the automatic measurement was 58% longer than the manual value. Precision of the automatic measurement, based upon triplicate DXA scans of 33 women, was 0.07 cm or 0.68%. To define normative data, the hip axis length was measured from femoral DXA scans of 471 female volunteers aged 40-92 scanned on 14 different Hologic QDR-1000 systems. Mean hip axis length was 10.5 cm, with a standard deviation of 0.62 cm. No significant relationship between hip axis length and age was found (r = 0.07, P = 0.15). Based on previously reported odds ratios corrected for femoral bone density, age, height, and weight, an automatic hip axis length measurement of 11.0 cm is associated with a twofold increase in hip fracture risk compared with a woman with an average hip axis length. A hip axis length value of 11.6 cm increases hip fracture risk by a factor of 4 compared with a woman with a normal hip dimension. We conclude that the hip axis length can be easily incorporated into existing DXA hip analysis software in combination with a bone density measurement.(ABSTRACT TRUNCATED AT 250 WORDS)


Involvement of Two Paralogous Methoprene-Tolerant Genes in the Regulation of Vitellogenin and Vitellogenin Receptor Expression in the Rice Stem Borer, Chilo suppressalis.
Besides the function of preventing metamorphosis in insects, the juvenile hormone (JH) plays a role in female reproduction; however, the underlying mechanism is largely unknown. The methoprene-tolerant (Met) protein belongs to a family of basic helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) transcription factors and functions as the JH intracellular receptor. In this study, two full length cDNAs encoding Met (CsMet1 and CsMet2) were isolated from the rice stem borer, Chilo suppressalis. Structural analysis revealed that both CsMet1 and CsMet2 exhibited typical bHLH, PAS-A, PAS-B, and PAC (PAS C terminal motif) domains. Comparative analysis of transcript level using reverse transcription-quantitative PCR (RT-qPCR) revealed that CsMet1 was predominant in almost all examined developmental stages and tissues. Treatment with methoprene in vivo induces the transcription of both CsMet1 and CsMet2. Notably, injection of dsCsMet1 and dsCsMet2 suppressed the expression levels of vitellogenin (CsVg) and Vg receptor (CsVgR). These findings revealed the potential JH signaling mechanism regulating C. suppressalis reproduction, and provided evidence that RNAi-mediated knockdown of Met holds great potential as a control strategy of C. suppressalis.


3D-OSEM versus FORE + OSEM: Optimal Reconstruction Algorithm for FDG PET with a Short Acquisition Time.
Objective In this study, we investigated the optimal reconstruction algorithm in fluorodeoxyglucose (FDG) positron emission tomography (PET) with a short acquisition time. Materials and Methods In the phantom study, six spheres filled with FDG solution (sphere size: 6.23-37 mm; radioactivity ratio of spheres to background = 8:1) and placed in a National Electrical Manufacturers Association phantom were evaluated. Image acquisition time was 15 to 180 seconds, and the obtained image data were reconstructed using each of the Fourier rebinning (FORE) + ordered subsets expectation-maximization (OSEM) and 3D-OSEM algorithms. In the clinical study, mid-abdominal images of 19 patients were evaluated using regions of interest placed on areas of low, intermediate, and high radioactivity. All obtained images were investigated visually, and quantitatively using maximum standardized uptake value (SUV) and coefficient of variation (CV). Results In the phantom study, FORE + OSEM images with a short acquisition time had large CVs (poor image quality) but comparatively constant maximum SUVs. 3D-OSEM images showed comparatively constant CVs (good image quality) but significantly low maximum SUVs. The results of visual evaluation were well correlated with those of quantitative evaluation. Small spheres were obscured on 3D-OSEM images with short acquisition time, but image quality was not greatly deteriorated. The clinical and phantom studies yielded similar results. Conclusion FDG PET images with a short acquisition time reconstructed by FORE + OSEM showed poorer image quality than by 3D-OSEM. However, images obtained with a short acquisition time and reconstructed with FORE + OSEM showed clearer FDG uptake and more useful than 3D-OSEM in the light of the detection of lesions.


Endogenous cell therapy improves bone healing.
Although bone repair is often a relatively rapid and efficient process, many bone defects do not heal. Because an adequate blood supply is essential for new bone formation, we hypothesized that augmenting new blood vessel formation by increasing the number of circulating vasculogenic progenitor cells (PCs) with AMD3100 and enhancing their trafficking to the site of injury with recombinant human parathyroid hormone (rhPTH) will improve healing. Critical-sized 3-mm cranial defects were trephined into the right parietal bone of C57BLKS/J 6 mice (N = 120). The mice were divided into 4 equal groups (n = 30 for each). The first group received daily subcutaneous injections of AMD3100 (5 mg/kg). The second group received daily subcutaneous injections of rhPTH (5 mg/kg). The third group received both AMD3100 and rhPTH. The fourth group received subcutaneous injections of saline. Circulating vasculogenic PC numbers, new blood vessel formation, and bony regeneration were assessed. Progenitor cell adhesion, migration, and tubule formation were assessed in the presence of rhPTH and AMD3100. Flow cytometry demonstrated that combination therapy significantly increased the number of circulating PCs compared with all other groups. In vitro, AMD3100-treated PCs had significantly increased adhesion migration, and tubule formation was assessed in the presence of rhPTH. Combination therapy significantly improved new blood vessel formation in those with cranial defect compared with all other groups. Finally, bony regeneration was significantly increased in the combination therapy group compared with all other groups. The combination of a PC-mobilizing and traffic-enhancing agent improved bony regeneration of calvarial defects in mice.


Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report.
We report on a case of difficult endotracheal intubation in a patient with marked tracheal deviation at an angle of 90 degrees combined with stenosis due to kyphoscoliosis with vertebral body fusion. After induction of general anesthesia, a proper laryngeal view was easily obtained using a videolaryngoscope. But a tracheal tube could not be advanced more than 3 cm beyond the vocal cords due to resistance, despite various attempts, including the use of small size tubes, full rotation of the tube tip, and fiberoptic bronchoscopy. Ultimately, the airway was successfully secured by placing a tube tip above the area of resistance and by additionally packing saline-soaked gauzes around the tracheal inlet to minimize gas leakage and to fasten the tube in the trachea.


Revascularization end points in stroke interventional trials: recanalization versus reperfusion in IMS-I.
The acute stroke literature lacks a standard convention regarding the critical end point of revascularization. Two distinct parameters may be clinically important: (1) recanalization of the primary arterial occlusive lesion (AOL) and (2) global reperfusion of the distal vascular bed. We sought to determine their relationship in the Interventional Management of Stroke (IMS) Phase I trial of combined intravenous (IV) and intraarterial (IA) recombinant tissue plasminogen activator. Sixty-one angiograms were reanalyzed using recanalization and reperfusion scores. The AOL Score was defined as: 0=no recanalization of the primary occlusion, I=incomplete or partial recanalization of the primary occlusion with no distal flow, II=incomplete or partial recanalization of the primary occlusion with distal flow, or III=complete recanalization of the primary occlusion with distal flow. The Thrombolysis in Myocardial Infarction (TIMI) Score was defined as: 0=no perfusion, 1=perfusion past the initial occlusion but no distal branch filling, 2=perfusion and incomplete or slow distal branch filling, or 3=full perfusion with filling of all distal branches. We compared the 2 scores with one another and with good clinical outcome (modified Rankin Score zero to 2). AOL and TIMI scores showed modest agreement (kappa, 0.30; confidence interval, 0.16 to 0.44). Good clinical outcome was seen in 49% of patients with AOL II/III scores (P=0.055) and 54% with TIMI 2/3 scores (P=0.019). The 2 methods did not significantly differ in predicting outcome (P=0.13). AOL recanalization and TIMI reperfusion scores comparably predict clinical outcome in this treatment paradigm. Other modalities may show different relationships between these 2 revascularization end points. Future studies should distinguish between these parameters semantically and methodologically.


Mosaic development of the olfactory cortex with Pax6-dependent and -independent components.
The olfactory cortex is the target area of olfactory bulb axons and is suggested to be derived from neuroepithelial progenitors of various ventricular domains during development. In the present study, we examined the development of the olfactory cortex, using the newly developed monoclonal antibody (mAb) 9-4c, which recognizes reticulon 1-A and -B. The mAb labeled neuroepithelial progenitors at the pallio-subpallial boundary (PSB) and their putative descendants in the deep layers of the olfactory cortex. In the Pax6 mutant embryo, labeling at the PSB was specifically lacking, and the number of immunopositive cells in the olfactory cortex was markedly reduced. In contrast, the guidepost neurons of olfactory bulb axons, lot cells, developed relatively normally in the superficial layer of the olfactory cortex in the mutant embryo. These guidepost neurons have been recently shown to originate in the pallium and eventually guide the initial projection of olfactory bulb axons. The olfactory bulb projection in the Pax6 mutant embryo also suggested the dualistic nature of the olfactory cortex development; the initial projection of olfactory bulb axons developed relatively normally, whereas the final projection of their collateral branches was severely defective.


Cord blood contains high numbers of autoimmune T cells recognizing multiple myelin proteins and acetylcholine receptor.
To analyze Ag-specific T cell autoimmunity in the newborn, umbilical cord blood cells of newborns were investigated by an immunospot assay for occurrence and numbers of cells secreting IFN-gamma after short-term culture in presence of myelin basic protein (MBP), proteolipid protein, myelin associated glycoprotein, nicotinic acetylcholine receptor and the synthetic MBP amino acid sequences 1-20, 63-88, and 110-128. These Ag were chosen because they represent putative targets for autoimmune attack in multiple sclerosis and myasthenia gravis. Surprisingly, numbers of T cells recognizing MBP, proteolipid protein, MBP peptides, and acetylcholine receptor were high in cord blood of newborns compared to peripheral blood of patients with neurologic diseases. No immunodominant T cell epitope could be discerned among the Ag included. The responses to purified protein derivate and PHA were lower among cord blood cells than peripheral blood cells of adults. Parallel enumeration of autoimmune T cells in cord blood and peripheral blood obtained from corresponding mothers at delivery, revealed that the high cell numbers in newborns were not a result of contamination from the mothers blood. The high numbers of T cells recognizing nervous system myelin proteins and acetylcholine receptor in cord blood could have importance for the mechanism and timing of tolerance induction, and also reflect excessive myelination and receptor maturation at birth.


A DNA 'barcode blitz': rapid digitization and sequencing of a natural history collection.
DNA barcoding protocols require the linkage of each sequence record to a voucher specimen that has, whenever possible, been authoritatively identified. Natural history collections would seem an ideal resource for barcode library construction, but they have never seen large-scale analysis because of concerns linked to DNA degradation. The present study examines the strength of this barrier, carrying out a comprehensive analysis of moth and butterfly (Lepidoptera) species in the Australian National Insect Collection. Protocols were developed that enabled tissue samples, specimen data, and images to be assembled rapidly. Using these methods, a five-person team processed 41,650 specimens representing 12,699 species in 14 weeks. Subsequent molecular analysis took about six months, reflecting the need for multiple rounds of PCR as sequence recovery was impacted by age, body size, and collection protocols. Despite these variables and the fact that specimens averaged 30.4 years old, barcode records were obtained from 86% of the species. In fact, one or more barcode compliant sequences (>487 bp) were recovered from virtually all species represented by five or more individuals, even when the youngest was 50 years old. By assembling specimen images, distributional data, and DNA barcode sequences on a web-accessible informatics platform, this study has greatly advanced accessibility to information on thousands of species. Moreover, much of the specimen data became publically accessible within days of its acquisition, while most sequence results saw release within three months. As such, this study reveals the speed with which DNA barcode workflows can mobilize biodiversity data, often providing the first web-accessible information for a species. These results further suggest that existing collections can enable the rapid development of a comprehensive DNA barcode library for the most diverse compartment of terrestrial biodiversity - insects.


Protease inhibitors for the treatment of hepatitis C virus infection.
The hepatitis C virus (HCV) has affected an estimate of 80 million individuals worldwide and is a strain of public health. Around 25-30% of patients in Europe and the US infected with HIV are coinfected with HCV. Despite treatment modalities containing a NS3/4A protease inhibitor in combination with pegylated interferon and ribavirin prior to 2013 improved SVR rates, the amount of severe side effects was high. Nowadays, oral direct-acting antivirals (DAAs) combination therapy offers excellent treatment efficacy, safety and tolerability. This review focuses on current literature and clinical evidence and their impact regarding NS3/4A protease inhibitors. In addition, pitfalls in treatment from HIV- and HBV-coinfected patients will also be discussed. In the era of DAA treatment, the third-generation pan-genotypic NS3/4A protease inhibitors (mainly grazoprevir, glecaprevir and voxilaprevir) show a high antiviral activity and genetic resistance barrier with cure rates of over 95% when combined with an NS5A inhibitor, irrespectively of baseline resistance associated variants (RASs) being present. These new key components of DAA combination therapy are impressive options to eradicate HCV in the so called difficult-to-treat population (e.g. compensated cirrhosis, end-stage renal disease and patients who failed previous DAA treatment).


Body mass index-mortality relationship in severe hypoglycemic patients with type 2 diabetes.
Hypoglycemia is associated with a higher risk of death. This study analyzed various body mass index (BMI) categories and mortalities of severe hypoglycemic patients with type 2 diabetes mellitus (DM) in a hospital emergency department. The study included 566 adults with type 2 diabetes who were admitted to 1 medical center in Taiwan between 2008 and 2009 with a diagnosis of severe hypoglycemia. Mortality data, demographics, clinical characteristics and the Charlson's Comorbidity Index were obtained from the electronic medical records. Patients were stratified into 4 study groups as determined by the National Institute of Health (NIH) and World Health Organization classification for BMI, and the demographics were compared using the analysis of variance and χ² test. Kaplan-Meier's analysis and the Cox proportional-hazards regression model were used for mortality, and adjusted hazard ratios were adjusted for each BMI category among participants. After controlling for other possible confounding variables, BMI <18.5 kg/m² was independently associated with low survival rates in the Cox regression analysis of the entire cohort of type 2 DM patients who encountered a hypoglycemic event. Compared to patients with normal BMI, the mortality risk was higher (adjusted hazard ratios = 4.9; 95% confidence interval [CI] = 2.4-9.9) in underweight patients. Infection-related causes of death were observed in 101 cases (69.2%) and were the leading cause of death. An independent association was observed between BMI less than 18.5 kg/m² and mortality among type 2 DM patient with severe hypoglycemic episode. Deaths were predominantly infection related.


[Assessment of anxiety in women during puerperium].
Many women experience various emotional disorders during puerperium characterized by high levels of anxiety. To analyse the level of anxiety in women during puerperium depending on age, education, marital status, number of pregnancies, route of delivery, and family situation. We enrolled 120 women between day 10 and 15 of puerperium without any previous psychiatric disorders. Pregnancy, delivery, and puerperium were without any morbidity and the newborns were healthy. The level of anxiety was measured using C. D. Spilberger's State-Trait Anxiety Inventory (STAI). The level of anxiety as a trait in women during puerperium was within normal limits, whereas the level of anxiety as a state was elevated. Primipara and women up to 20 years of age require special attention during psycho-preventive treatment due to increased level of anxiety as a trait during puerperium. Employment and family situation determine the level of anxiety as a state after delivery. Identification of women with a higher level of anxiety as a state during puerperium may provoke early medical intervention in this group of women and thus contribute to improvement in the quality of life of the woman and conditions for future development of the neonate.


Beyond-Cassie Mode of Wetting and Local Contact Angles of Droplets on Checkboard-Patterned Surfaces.
Droplet wetting and distortion on flat surfaces with heterogeneous wettability are studied using the 3D Shan-Chen pseudopotential multiphase lattice Boltzmann model (LBM). The contact angles are compared with the Cassie mode, which predicts an apparent contact angle for flat surfaces with different wetting properties, where the droplet size is large compared to the size of the heterogeneity. In this study, the surface studied consists in a regular checkboard pattern with two different Young's contact angles (hydrophilic and hydrophobic) and equal surface fraction. The droplet size and patch size of the checkboard are varied beyond the limit where Cassie's equation is valid. A critical ratio of patch size to droplet radius is found below which the apparent contact angle follows the Cassie mode. Above the critical value, the droplet shape changes from a spherical cap to a more distorted form, and no single contact angle can be determined. The local contact angles are found to vary along the contact line between minimum and maximum values. The droplet is found to wet preferentially the hydrophilic region, and the wetted area fraction of the hydrophilic region increases quasi-linearly with the ratio between patch and droplet sizes. We propose a new equation beyond the critical ratio, defining an equivalent contact angle, where the wetted area fractions are used as weighting coefficients for the maximum and minimum local contact angles. This equivalent contact angle is found to equal Cassie's contact angle.


Trends and characteristics of AIDS mortality in the Rio de Janeiro city after the introduction of highly active antiretroviral therapy.
We examined the characteristics of AIDS mortality in Rio de Janeiro city from 1995 to 2003. During this period, highly active antiretroviral therapy with protease inhibitors was made available, and it changed the pattern of the epidemics. There was a 47.5% reduction in the number of AIDS deaths within the period, with an increase in the proportion of women among the deceased; their schooling was lower than that of the men, similar to the trends of the national-level epidemics. The main place of death changed from university hospitals to emergency rooms. The proportion of cases reported to the National Diseases Surveillance System (SINAN) reported only through the death certificate remained high. Although there is free distribution of antiretrovirals by the public health system, many patients still lack access to diagnosis and treatment. We need to give priority to access to anti-HIV testing and treatment, to increase the quality of care and to look into the issue of adherence in order to further reduce AIDS mortality.


Recreational use of erectile dysfunction medications in undergraduate men in the United States: characteristics and associated risk factors.
Mounting evidence indicates that erectile dysfunction medications (EDMs) have become increasingly used as a sexual enhancement aid among men without a medical indication. Recreational EDM use has been associated with increased sexual risk behaviors, an increased risk for STIs, including incident HIV infection, and high rates of concomitant illicit drug use. The aim of the present study was to investigate the characteristics and associated risk factors for recreational EDM use among young, healthy, undergraduate men. A cross-sectional sample of 1,944 men were recruited from 497 undergraduate institutions within the Unites States between January 2006 and May 2007. The survey assessed patterns of EDM use, as well as demographic, substance use, and sexual behavior characteristics. Four percent of participants had recreationally used an EDM at some point in their lives, with 1.4% reporting current use. The majority of recreational EDM users reported mixing EDMs with illicit drugs and particularly during risky sexual behaviors. Recreational EDM use was independently associated with increased age, gay, or bisexual sexual orientation, drug abuse, lifetime number of sex partners, and lifetime number of "one-night stands." Recreational EDM users also reported a 2.5-fold rate of erectile difficulties compared to nonusers. Overall, recreational use of EDMs was associated with sexual risk behaviors and substance abuse; however, a relatively small proportion of undergraduates reported using EDMs. Results also suggest that a sizable portion of recreational EDM users are heterosexual men, and that use does not solely occur within the environments of venues that cater to men having sex with men.


Annular skin lesions in infancy.
Annular skin lesions have a unique morphology, and the dramatic appearance of these skin eruptions in infants can cause concern for parents and clinicians. Annular lesions appearing during infancy (defined here as birth to 1 year of age) lend to a broad differential, ranging from benign cutaneous disorders to severe systemic diseases. This review summarizes the pathogenesis, clinical and histopathologic findings, and management options of possible etiologies for annular skin lesions in infants, including annular erythema of infancy, neonatal lupus erythematosus, dermatophyte infections, hemorrhagic edema of infancy, and urticaria multiforme.


Corrected splicing of a chicken ovalbumin gene transcript in mouse L cells.
Mouse thymidine-kinase-negative L cells were transformed with a cloned chicken ovalbumin gene linked to the cloned thymidine kinase gene from herpes simplex virus type 1. Most thymidine-kinase-positive clones contained one or more copies of the ovalbumin gene, which were stably maintained for at least 6 months during continuous culture under selective conditions. Transcription of the ovalbumin gene was detected at a low level, producing RNA molecules that were correctly spliced and polyadenylylated by comparison with genuine ovalbumin mRNA. However, the 5' end of these RNA molecules does not correspond to that of ovalbumin mRNA.


Adenovirus-mediated delivery of the human IFN-γ gene potentiates the cytotoxicity of daunorubicin against leukemic cells through downregulation of the α4β1 integrin/ILK/apoptosis pathway.
The recurrence of acute myeloid leukemia (AML) is primarily attributed to drug resistance and minimal residual disease. In addition, adhesion of hematopoietic tumor cells to bone marrow extracellular matrix via β1 integrins (α4β1 and α5β1) is crucial in this process. In the current study, the viability and antiapoptotic ability of U937 cells exposed to daunorubicin (DNR) were shown to be enhanced when cocultured with the mesenchymal stem cells (MSCs) or MSCs transduced with a recombinant adeno-LacZ vector (MSCs-LacZ), followed by upregulation of the adhesion rate of leukemic cells. Notably, cell viability, antiapoptotic and adhesive ability were reversed when U937 cells were cocultured with the MSCs transduced with a recombinant adeno-IFN-γ vector (MSCs-IFN-γ). Transwell assay showed that cell-cell contact is essential for the protective effects of unmodified MSC and the antitumor effects of IFN-γ-expressing MSCs. Western blot analysis and caspase activity assay results indicated that the α4β1 integrin/ILK/apoptosis pathway contributes to the combination effects of DNR and MSCs-IFN-γ, which was further confirmed by the results of the α4β1 integrin siRNA experiments. Thus, gene-modified MSCs expressing IFN-γ may enhance the cytotoxicity of DNR against leukemic cells through downregulation of the α4β1 pathway and may present a novel promising therapeutic strategy for AML.


Study on the practices of silage production and utilization on Brazilian dairy farms.
Dairy farmers across Brazil were invited to participate in a study on silage production and utilization practices. Two hundred sixty farmers filled out a questionnaire, which was made available on a website. The questionnaire consisted of 14 questions, including information about the characteristics of the herd (n=3), the crop(s) used in the ensiling process, the use of additives, the harvest (n=3), the type of silo (n=1), aspects related to sealing (n=2), and management practices applied during feed-out (n=3). Farmers were also asked a final question about the main barriers they faced when producing and using silage. The main dairy-producing regions of Brazil had a strong influence on the number of participants. The profiles of farmers were heterogeneous and divided into 5 groups, which was considered a positive attribute of the study, allowing better analysis and assessment of current circumstances. Corn was the most widely grown crop for silage. Sorghum, tropical grasses, and sugarcane were the other species most cited. Additives were used by a small number of farmers (27.7%). Approximately 40% of farmers still depended on loaned equipment or outsourced services. The pull-type forage harvester was the main piece of equipment used on dairy farms (90.4%). Only 54.6% of respondents answered that they sharpen their harvester knives daily. Horizontal silos (bunker and stack) were the structures most commonly used to store silage. Most farmers sealed silos with double-sided plastic film (black-on-white) and with soil. However, almost one-fifth of all farmers still use black plastic. Manual removal of silage from the silos was practiced at most farms (i.e., the lack of equipment was also reflected in the stage of silage utilization). Disposal of spoiled silage before inclusion in the livestock feed was not a common practice on the farms. The main barriers encountered on the farms were lack of equipment, lack of manpower, and climatic variations. The results of this research may guide researchers, industries, extension workers, and governments to seek efficiency in milk production on farms using silage in the diet of livestock throughout the year or during part of the year in Brazil.


Safety and feasibility of lumbar spine for intralaminar screw fixation: a computed tomography-based morphometric study.
The use of intralaminar screws (ILS) in spinal surgery has experienced a recent increase in popularity. The aim of this study is to define the morphological parameters of the lumbar laminas so that guidance may be defined for ILS placement. The study involved the evaluation of lumbar computed tomography (CT) images of patients. Two hundred thirty-five patients (127 male, 108 female) were included in the study. The mean patient age was 44.2 years (19-78 years). The measured parameters of the lamina were the transverse inner diameter, transverse outer diameter (lamina width), lamina length, subdural space (safe zone), and spinolaminar angle for each lumbar level (L1-L5). The mean transverse outer diameter (L1-L5) ranged from 7.2-7.8 mm, and mean transverse inner diameter ranged from 2.5-3.0 mm. The lamina of L3 had the largest width and the lamina of L1 and L5 the smallest. The mean lamina length was 26.6 mm, ranging from 21.0-34.0 mm, and the mean spinolaminar angle was 124.7°, ranging from 111-135°. The L1 level had the shortest mean lamina length and L4 the lowest spinolaminar angle. Mean subdural space (safe zone), which was narrowest at the L5 level, was 2.4 mm, ranging from 1.3-3.6 mm. ILS of the appropriate size (3.5-4.5 mm) and length (20 and 25 mm) can be used safely in the lumbar spine. However, further biomechanical studies should be performed to measure strength of the fixation.


Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.
Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited neuropathies. Mutations in approximately 45 genes have been identified as being associated with CMT. Nevertheless, the genetic etiologies of at least 30% of CMTs have yet to be elucidated. Using a genome-wide linkage study, we previously mapped a dominant intermediate CMT to chromosomal region 3q28-q29. Subsequent exome sequencing of two affected first cousins revealed heterozygous mutation c.158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gβ4), to cosegregate with the CMT phenotype in the family. Further analysis of GNB4 in an additional 88 unrelated CMT individuals uncovered another de novo mutation, c.265A>G (p.Lys89Glu), in this gene in one individual. Immunohistochemistry studies revealed that Gβ4 was abundant in the axons and Schwann cells of peripheral nerves and that expression of Gβ4 was significantly reduced in the sural nerve of the two individuals carrying the c.158G>A (p.Gly53Asp) mutation. In vitro studies demonstrated that both the p.Gly53Asp and p.Lys89Glu altered proteins impaired bradykinin-induced G-protein-coupled-receptor (GPCR) signaling, which was facilitated by the wild-type Gβ4. This study identifies GNB4 mutations as a cause of CMT and highlights the importance of Gβ4-related GPCR signaling in peripheral-nerve function in humans.


Serum Cholinesterase Is Inversely Associated with Body Weight Change in Men Undergoing Routine Health Screening.
The purpose of this study is to investigate the relationships between serum cholinesterase and body weight change, in addition to incident obesity defined as a body mass index (BMI) of 25 kg/m(2) or greater. A retrospective 5-year follow-up study was conducted. The crude incidence and hazard ratios (HRs) of obesity adjusted for the BMI and other confounders were calculated for cholinesterase quartiles in 1,412 men and 921 women. Partial correlation coefficients (PCCs) were calculated between cholinesterase and changes in the BMI during the 5-year follow-up period adjusted for age and other confounders and the change in the BMI were compared among cholinesterase quartiles in 1,223 men and 681 women. During the 5-year follow-up period, 149 men (10.6%) and 65 women (7.1%) developed obesity. The adjusted HRs of obesity decreased, although the crude incidence of obesity increased along the quartiles of cholinesterase in men. The adjusted HRs of obesity for the first (lowest), second and third quartiles of cholinesterase were 2.02 (p=0.006), 1.45 (p=0.122), and 1.28 (p=0.265), respectively compared with the highest quartile in men. The PCC between the baseline level of cholinesterase and change in the BMI was -0.16 (p<0.001) in men. The mean changes in BMI for 5 years were 0.31 kg/m(2), 0.17 kg/m(2), 0.01 kg/m(2) and -0.04 kg/m(2), respectively in the first, second, third and fourth quartiles of cholinesterase in men (p=0.005). Neither incident obesity nor weight gain was significantly associated with cholinesterase in women. The serum cholinesterase level was inversely associated with body weight change, as well as incident obesity, after adjusted for the BMI in men.


Endoplasmic reticulum stress increases glucose-6-phosphatase and glucose cycling in liver cells.
Impaired regulation of hepatic glucose production is a characteristic feature of the metabolic syndrome, a cluster of diseases that includes obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. It has been proposed that sustained endoplasmic reticulum stress, which appears to occur in obesity and diabetes, modulates insulin action in the liver. In this study, we show that experimental induction of endoplasmic reticulum stress increases expression and activity of glucose-6-phosphatase and the capacity for glucose release and glucose cycling in primary rat hepatocytes and H4IIE liver cells. Increased expression of the catalytic subunit of glucose-6-phosphatase was largely a result of increased transcription. Deletion analysis of the glucose-6-phosphatase promoter identified an endoplasmic reticulum stress-responsive region located between -233 and -187 with respect to the transcriptional start site. Experimental induction of endoplasmic reticulum stress increased the activity of c-jun N-terminal kinase. Prevention of endoplasmic reticulum stress-mediated activation of c-jun N-terminal kinase reduced the expression of the catalytic subunit of glucose-6-phosphatase, glucose-6-phosphatase activity, glucose release, and glucose cycling. These data demonstrate that sustained endoplasmic reticulum stress in the hepatocyte provokes adaptations, mediated in part via activation of c-jun N-terminal kinase, that act to increase hepatocellular capacity for glucose release and glucose cycling.


Dynamic monitoring of serum liver function indexes in patients with COVID-19.
Some patients with the novel 2019 coronavirus disease (COVID-19) display elevated liver enzymes. Some antiviral drugs that can be used against COVID-19 are associated with a risk of hepatotoxicity. To analyze the clinical significance of the dynamic monitoring of the liver function of patients with COVID-19. This was a retrospective study of patients diagnosed with COVID-19 in January and February 2020 at the Department of Infection, Shantou Central Hospital. The exclusion criteria for all patients were: (1) History of chronic liver disease; (2) History of kidney disease; (3) History of coronary heart disease; (4) History of malignancy; or (5) History of diabetes. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase, and total bilirubin of patients with COVID-19 were measured on days 1, 3, 7 and 14 after admission, and compared to non-COVID-19 patents. Twelve patients with COVID-19 (seven men and five women) and twelve controls (eight men and four women) were included. There were one, two, and nine patients with severe, mild, and moderate COVID-19, respectively. There were no differences in age and sex between the two groups (both P > 0.05). No significant differences were found in albumin, ALT, AST, γ-glutamyltransferase, or total bilirubin between the controls and the patients with COVID-19 on day 1 of hospitalization (all P > 0.05). Serum albumin showed a decreasing trend from days 0 to 7 of hospitalization, reaching the lowest level on day 7. Total bilirubin was higher on day 3 than on day 7. ALT, AST, and γ-glutamyltransferase did not change significantly over time. The severe patient was observed to have ALT levels of 67 U/L and AST levels of 75 U/L on day 7, ALT of 71 U/L and AST of 35 U/L on day 14, and ALT of 210 U/L and AST of 123 U/L on day 21. Changes in serum liver function indicators are not obvious in the early stage of COVID-19, but clinically significant changes might be observed in severe COVID-19.


Vascular wall reactivity in conductance and resistance arteries: differential effects of insulin resistance.
Insulin resistance is associated with an increased risk of cardiovascular disease that is probably related to abnormalities of vascular wall function. The JCR:LA-cp rat is a unique animal model of human vascular disease that exhibits a profound insulin resistance, vasculopathy, and cardiovascular disease, and allows study of the relationships between insulin resistance and vascular function. Conductance and resistance arteries serve different functions, thus vascular disease may affect these types of artery differently. Concentration-response curves to norepinephrine, phenylephrine, and acetylcholine were studied in conductance vessels (aortic rings) and resistance vessels (mesenteric arteries) from 12-week-old male obese and lean JCR:LA-cp rats. The aortic rings and mesenteric arteries from obese rats showed increased maximal response to phenylephrine compared with those from lean rats, whereas only the mesenteric arteries from obese rats showed increased maximal response to norepinephrine. In aortic rings, relaxation to acetylcholine was similar for both genotypes, but the mesenteric arteries of obese rats showed impaired relaxation to acetylcholine. We conclude that the sensitivity to vasoconstriction is enhanced in aortic rings and mesenteric arteries of obese male JCR:LA-cp rats, but endothelial function is impaired only in the mesenteric resistance arteries of these animals. Hence functional aberrations in the obese, insulin-resistant state are more pronounced in mesenteric resistance arteries than in a major conductance artery.


Does dynamic immobilization reduce chondrocyte apoptosis and disturbance to the femoral head perfusion?
The purpose of this study is to investigate whether the dynamic hip immobilization is more favourable for lessening ischemic injury to the immature femoral head than a static immobilization. 152 Japanese white rabbits were divided into four groups randomly, and the hips were immobilized into "human" position (group A), "frog leg" position (group B) and "dynamic frog leg" position (group C). Group D was used as control. Ten rabbits in each group were killed, and the hip specimens were harvested at 1, 2, and 3 weeks after immobilization. Bcl-2/Bax expression balance and chondrocytes apoptosis were analyzed. The remaining eight rabbits in each group were used to measure the blood supply of capital femoral epiphysis by selective vascular perfusion with Indian ink. The Bcl-2/Bax expression ratio in group C was significantly increased than that in group A and B (p<0.001), while that was not significantly different from control group (p=0.0592). At three weeks after immobilization, the average apoptotic ratio was 36.7%, 45.8%, and 26.7% in group A, B and C, respectively (p<0.01). There was no significant difference between group C and normal control (p=0.0597). The perfusion ratio was 0.03±0.03, 0.03±0.02, and 0.08±0.03 in group A, B and C respectively, and 0.12±0.04 in control group (p<0.05). Thus, the dynamic immobilization model exhibited a relatively less chondrocytes apoptosis and disturbance to the femoral head perfusion than other immobilizations in vivo, which therefore may be useful for reducing avascular necrosis following the treatment of developmental dysplasia of the hip.