Widely tunable O-band lithium niobite/III-V transmitter.
The ever-increasing traffic has been driving the demand for compact, high-speed, and low-power-consumption optical transmitters. Thin-film lithium niobite (TFLN) platforms have emerged as promising photonic integrated solutions for next-generation optical transmitters. In this study, we demonstrated the first widely tunable optical transmitter based on a butt-coupling a TFLN modulator with an electrically pumped tunable laser. The tunable laser exhibited a side-mode suppression ratio of > 60 dB, linewidth of 475 kHz, and wavelength-tuning range of over 40 nm. The TFLN modulator presented a voltage-length product of 2.9 V·cm and an electro-optic response of 1.5 dB roll-off at 50 GHz. The optical transmitter support data rate was as high as 160 Gb/s.


Possible bioactive conformations of alpha-melanotropin.
By comparing the results of energy calculation for alpha-MSH and its semirigid analogues Ac-[ Cys4 , Cys10 ]-alpha- MSH4 -10-NH2, Ac-[ Cys4 , Cys10 ]-alpha- MSH4 -13-NH2, and [ Cys4 - Cys10 ]-alpha-MSH, a detailed description of two possible bioactive conformations for the 'specific' central site of alpha- MSH6 -9 is proposed representing variants of chain-reversal structure. A possible explanation of the rise in melanotropic activity of the latter two semirigid analogues is presented.


Two-year clinical performance of Class V resin-modified glass-lonomer and resin composite restorations.
While a one-year report had been previously published, this study was undertaken to evaluate the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over two years. Thirty-seven pairs of restorations of FujI II LC and Z 250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation. Restorations were clinically evaluated at baseline, 6, 12, 18 and 24 months using modified Ryge/USPHS criteria. No statistically significant difference (p = 0.13) was observed in the overall performance of the materials. Retention was 96% for the resin-modified glass ionomer and 81% for the resin composite, with no additional restorations of either material lost after one year. As previously reported, retention of the Z 250 restorations at six months was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives. The resin composite restorations generally had a better appearance, with a 100% alpha rating in color match, versus 85% for the resin-modified glass ionomer.


Preparation of Xanthene-TEMPO Dyads: Synthesis and Study of the Radical Enhanced Intersystem Crossing.
We prepared a rhodamine-TEMPO chromophore-radical dyad (RB-TEMPO) to study the radical enhanced intersystem crossing (REISC). The visible light-harvesting chromophore rhodamine is connected with the TEMPO (a nitroxide radical) via a C-N bond. The UV-vis absorption spectrum indicates negligible electron interaction between the two units at the ground state. Interestingly, the fluorescence of the rhodamine moiety is strongly quenched in RB-TEMPO, and the fluorescence lifetime of the rhodamine moiety is shortened to 0.29 ns, from the lifetime of 3.17 ns. We attribute this quenching effect to the intramolecular electron spin-spin interaction between the nitroxide radical and the photoexcited rhodamine chromophore. Nanosecond transient absorption spectra confirm the REISC in RB-TEMPO, indicated by the detection of the rhodamine chromophore triplet excited state; the lifetime was determined as 128 ns, which is shorter than the native rhodamine triplet state lifetime (0.58 μs). The zero-field splitting (ZFS) parameters of the triplet state of the chromophore were determined with the pulsed laser excited time-resolved electron paramagnetic resonance (TREPR) spectra. RB-TEMPO was used as a photoinitiator for the photopolymerization of pentaerythritol triacrylate (PETA). These studies are useful for the design of heavy atom-free triplet photosensitizers, the study of the ISC, and the electron spin dynamics of the radical-chromophore systems upon photoexcitation.


Epidemiology of human parvovirus B19 in children with sickle cell disease.
Human parvovirus (HPV) B19 causes significant morbidity and mortality in children with sickle cell disease (SCD), but little data are published about the epidemiology of HPV B19 infection and its associated complications in this patient population. In this study, prevalence and incidence rates of HPV B19 were determined in 633 patients with SCD followed at The Children's Hospital of Philadelphia between November 1996 and December 2001. Thirty percent (30%) were HPV B19 immunoglobulin G (IgG) positive at first testing, and the 70% without evidence of past HPV B19 infection were tested annually. One hundred ten patients developed evidence of HPV B19 infection for an incidence rate of 11.3 per 100 patient years. Sixty-eight episodes of HPV B19-induced transient red cell aplasia occurred with the following clinical events: fever (89.7%), pain (61.8%), acute splenic sequestration (19.1%), and acute chest syndrome (11.8%). Pain, fever, and acute splenic sequestration were more frequent events with acute HPV B19 infections compared with acute events in uninfected patients. The results of this epidemiologic study, the largest and most comprehensive to date, justify the development of HPV B19 prevention strategies to diminish the frequent and often severe complications associated with HPV B19 infections in patients with SCD.


Numerical Approach to the Plasmonic Enhancement of Cs2AgBiBr6 Perovskite-Based Solar Cell by Embedding Metallic Nanosphere.
Lead-free Cs2AgBiBr6 perovskites have emerged as a promising, non-toxic, and eco-friendly photovoltaic material with high structural stability and a long lifetime of carrier recombination. However, the poor-light harvesting capability of lead-free Cs2AgBiBr6 perovskites due to the large indirect band gap is a critical factor restricting the improvement of its power conversion efficiency, and little information is available about it. Therefore, this study focused on the plasmonic approach, embedded metallic nanospheres in Cs2AgBiBr6 perovskite solar cells, and quantitatively investigated their light-harvesting capability via finite-difference time-domain method. Gold and palladium were selected as metallic nanospheres and embedded in a 600 nm thick-Cs2AgBiBr6 perovskite layer-based solar cell. Performances, including short-circuit current density, were calculated by tuning the radius of metallic nanospheres. Compared to the reference devices with a short-circuit current density of 14.23 mA/cm2, when a gold metallic nanosphere with a radius of 140 nm was embedded, the maximum current density was improved by about 1.6 times to 22.8 mA/cm2. On the other hand, when a palladium metallic nanosphere with the same radius was embedded, the maximum current density was improved by about 1.8 times to 25.8 mA/cm2.


Representation of the direct correlation function of the hard-sphere fluid.
An accurate representation of the structural pair correlation functions of the hard sphere (HS) fluid up to the freezing density is proposed which combines the pole expression for the total correlation function h(r), the Ornstein-Zernike equation, and molecular dynamics (MD) computer simulation data. In the scheme, h(r) is expressed in terms of a set of pole parameters, which reveals how the tail of the Fourier transform of h(r) contains information on the discontinuities in the derivatives of the direct correlation function (DCF). This formulation leads to a DCF expressed as the sum of a numerically obtainable part and an analytic part which consists of elementary integral terms, some of which are found to give rise to the discontinuities. An exact formula for the magnitude of these discontinuities is derived, which indicates that there is a particular density (ρ≅0.133) below which the magnitude of the discontinuities decreases with increasing order of the derivative. With the accurate MD simulation data the set of parameters that specifies h(r) was determined. These can be used to obtain the different structural functions of the HS fluid, and following the calculation stages of the pole structure scheme the DCF is obtained. From this route to the DCF the second pole of the HS fluid can be determined and the non-negligible role of the "out of core" part of the DCF at high densities is revealed. The density-dependent separation range where the two pole approximation represents well the h(r) has been determined.


A thermal heat summation model to predict the duration of the gonotrophic cycle of Culiseta melanura in nature.
This study determined the effect of temperature on the gonotrophic cycle of Culiseta melanura and developed a thermal heat summation model to calculate its duration under field conditions. A colony of Cs. melanura was used from New Jersey (F13-F17 generation) and the length of the gonotrophic cycle was observed at 2, 10, 16, 22, 28, 32 and 34 degrees C. None of the mosquitos survived at 2 degrees C or 34 degrees C and none laid fertile eggs at 32 degrees C. A linear regression analysis on the data showed that the thermal minimum for ovarian development was 6.4 degrees C and 95.87 degree days were required above 6.4 degrees C to complete one gonotrophic cycle. A thermal heat summation model is presented to allow calculation of the duration of the gonotrophic cycle under field conditions when average temperatures are known.


Synthesis, structure, and properties of O6 -Corona[3]arene[3]tetrazines.
O6 -Corona[3]arene[3]tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one-pot reaction from the nucleophilic aromatic substitution reaction between 1,4-dihydroxybenzene derivatives and 3,6-dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron-deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O6 -corona[3]arene[3]tetrazines to be suitable macrocyclic receptors for electron-rich guests.


Bioactive Compounds, Chemical Composition, and Medicinal Value of the Giant Puffball, Calvatia gigantea (Higher Basidiomycetes), from Turkey.
In this study, the compositions of Calvatia gigantea were first analyzed in order to elucidate its chemical basis for development as a health-enhancing food or medicine. This study investigates the chemical composition (nutritional value; phenolic, sugar and fatty acid content; aroma compounds) and antioxidant properties (radical scavenging activity, reducing power, and inhibition of lipid peroxidation) of C. gigantea. The results showed that C. gigantea contains phenolic compounds and sugars and is rich in polyunsaturated fatty acids (67.93%), proteins (34.37%), and carbohydrates (51.97%). The most abundant compounds were gentisic acid (23.26 µg/g; as a phenolic compound), trehalose (9.78 g/100g; as a sugar), and hexanal (34.71%; as an aroma compound). These findings suggest that C. gigantea might be a promising source of medicine and has the potential to be a health food and food supplementary product.


Functional and molecular expression of the proton-coupled oligopeptide transporters in spleen and macrophages from mouse and human.
The aim of this study was to determine the expression and function of proton-coupled oligopeptide transporters (POTs) in spleen and macrophages and their contribution to innate immune response induced by bacterial peptidomimetics γ-iE-DAP and MDP. Quantitative real-time PCR (qRT-PCR) and Western blot results revealed the mRNA and protein expression of PepT2, PhT1, and PhT2, but not PepT1, in the spleen of mice and humans. In comparison to lymphocytes of the spleen, macrophages had higher transcript levels of PepT2 and PhT2. The cellular uptake of Ala-Lys-AMCA in mouse splenic macrophages was pH-dependent with maximum uptake at pH 6.0, and the kinetic parameters were K(m) = 75.5 ± 14.3 μM and V(max) = 25.4 ± 2.1 pmol/min per mg protein. The uptake of Ala-Lys-AMCA by mouse splenic macrophages was not inhibited by histidine but was significantly inhibited by glycyl-sarcosine (GlySar) and carnosine (P < 0.01), and by bacterial peptidomimetics γ-iE-DAP and MDP, ligands of nucleotide-binding oligomerization domain (NOD)-containing proteins. Carnosine and GlySar, but not histidine, attenuated the inflammatory response induced by γ-iE-DAP and MDP in mouse splenic macrophages. Functional expression of POTs was also demonstrated in THP-1 cells, and dipeptides reduced the immune response induced by γ-iE-DAP. In conclusion, our findings are novel by providing important information on the molecular and functional expression of POTs in the spleen. Moreover, it appears that the PepT2-mediated uptake of γ-iE-DAP and MDP in macrophages further contributes to the innate immune response.


Information processing and attentional functioning in the developmental course of schizophrenic disorders.
This article examines the evidence that certain deficits in information processing and attentional functioning are present across populations at risk for schizophrenic disorder, with active schizophrenic psychotic symptomatology, and in relative remission after a schizophrenic psychosis. In addition, the evidence that some deficits in processing information occur only in the actively psychotic period is inspected. Deficits in vigilance tasks with high-processing loads, in forced-choice span of apprehension for large arrays, and in serial recall for items that involve active rehearsal occur across risk populations, actively symptomatic schizophrenic patients, and relatively remitted schizophrenic patients. These deficits may reflect vulnerability factors for schizophrenic disorders. Reaction time crossover, dichotic listening, backward masking, and referential communication deficits might also be vulnerability indicators. These deficits may be related to a reduction in the processing capacity that is available for task-relevant cognitive operations in persons vulnerable to schizophrenic disorder, which could, in turn, be caused by several different underlying cognitive anomalies. Cognitive deficits that have been found only during actively psychotic periods or in chronic schizophrenic patients, such as poorer recognition of briefly presented, single, familiar letters or numbers, are characterized by low demands on processing capacity. These deficiencies may be caused by further reduction in available processing capacity or a temporary disruption of automatic as well as attention-demanding processes; they could also reflect a stable, more severe cognitive deficit in a subtype of schizophrenic disorder.


Organ culture of foetal rat pancreas. Effects of parabiotic culture with foetal adrenal glands.
The differentiation and growth of the foetal rat pancreas (20 days postcoitum) was studied in parabiotic organ culture with foetal adrenal tissue. In such co-cultures, characteristic pancreatic morphology was preserved and further acinar cell differentiation was fostered. Acinar cells contiunued to represent about 65% of the total explant volume following short-term incubation. The selective islet cell proliferation, previously observed in control pancreatic explants cultured alone, did not occur when adrenals were co-cultured. In addition, the amylase content of the incubation media and of the explanted pancreatic tissue remained high with adrenal co-culture, while the insulin content of the media and of the explanted tissue was markedly suppressed when compared to control pancreatic explants cultured alone. The effects of the adrenal in maintaining the differentiated acinar component of the pancreas and suppressing media insulin concentration diminished over extended incubation. The addition of adrenals to culture of foetal pancreatic explants after 6 days of control culture (at a time when differentiated acinar cells were not identifiable in the explant) did not result in redifferentiation of the acinar component, but did markedly depress media insulin content. Removal of adrenals after 4 days of co-culture resulted in an immediate rise in media insulin concentration and a rapid decline in pancreatic acinar mass. An adrenal-exocrine pancreatic axis is proposed and it is suggested that foetal adrenal secretions may play an important role in the development of the exocrine pancreas in vivo as well as in vitro.


Histomorphometric evaluation of six dental implant surfaces after early loading in augmented human sinuses.
This study investigated the bone-to-implant contact (BIC) and osteoconductive capacity (OC) of 6 different implant surfaces after early loading in humans. Two implants with different surfaces were placed side-by-side in the grafted (n= 5) and nongrafted (n = 1) sinuses of 3 volunteers. Single-tooth restorations were delivered 60 days later. After 6 months of full occlusal loading, implants were retrieved in block sections for histomorphometric analysis. One implant (acid etched) placed in grafted bone failed when loaded. There were no other complications. In grafted bone, the microtextured surface achieved the highest BIC value (94.08%), followed by the oxidized (77.32%), hydroxyapatite (HA) (74.51%), sandblasted and acid-etched (51.85%), and titanium plasma-sprayed (TPS) (41.48%) surfaces. In native bone, the acid-etched surface achieved a higher BIC value (69.03%) than the HA surface (59.03%). The highest OC value in grafted bone was exhibited by the microtextured surface (34.31%), followed by the HA (28.62%), sandblasted and acid-etched (25.08%), oxidized (17.55%), and TPS (-20.47%) surfaces. The HA surface exhibited a higher OC value (30.39%) in native bone compared with the acid-etched surface (24.0%). As a whole, highest BIC and OC values were exhibited by the microtextured surface, and lowest values were exhibited by the TPS surface. All other surfaces demonstrated excellent BIC (>50%) but varied in OC (range = 17.55%-28.62%). These findings are tempered by the limited scope and sample size of the study and should be considered preliminary. More research is needed to determine the impact of implant surface texture on BIC and OC.


Interleukin-12 protects mice against disseminated infection caused by Paracoccidioides brasiliensis but enhances pulmonary inflammation.
Paracoccidioides brasiliensis is a facultative, intracellular pathogen causing the most important deep mycosis in Latin America. As the production of IFN-gamma and induction of cell-mediated immunity to P. brasiliensis is of critical importance in host defense, the immunotherapeutic effect of exogenous IL-12 administration was studied in a murine model of susceptibility to pulmonary infection. rIL-12 treatment led to a less disseminated disease, as confirmed by decreased fungal loads in liver and spleen. Administration of rIL-12 did not affect fungal growth in the lungs, although it did induce an augmented pulmonary mononuclear cell inflammation. IL-12 treatment induced an early (week 1) increase in pulmonary IFN-gamma, but decreased cytokine and specific antibody (IgG1 and IgG3) production at week 8 after infection. These results show that IL-12 administration induces a less severe infection, but the high inflammatory response detected in the lungs precludes its possible use as a new therapeutic tool for severe paracoccidioidomycosis.


Struct2GO: protein function prediction based on graph pooling algorithm and AlphaFold2 structure information.
In recent years, there has been a breakthrough in protein structure prediction, and the AlphaFold2 model of the DeepMind team has improved the accuracy of protein structure prediction to the atomic level. Currently, deep learning-based protein function prediction models usually extract features from protein sequences and combine them with protein-protein interaction networks to achieve good results. However, for newly sequenced proteins that are not in the protein-protein interaction network, such models cannot make effective predictions. To address this, this article proposes the Struct2GO model, which combines protein structure and sequence data to enhance the precision of protein function prediction and the generality of the model. We obtain amino acid residue embeddings in protein structure through graph representation learning, utilize the graph pooling algorithm based on a self-attention mechanism to obtain the whole graph structure features, and fuse them with sequence features obtained from the protein language model. The results demonstrate that compared with the traditional protein sequence-based function prediction model, the Struct2GO model achieves better results. The data underlying this article are available at https://github.com/lyjps/Struct2GO.


[Experimental gastrointestinal motility].
Gastrointestinal motility is a major field of research today; however, despite there being a huge amount of available data in the literature, its exact role as a diagnostic tool has yet to be defined. The purpose of this paper is to describe some of the existing experimental models and methods for conducting motility studies.


Perceptions and Practices Regarding Atopic Dermatitis: A Survey.
Parents (N = 392) completed a survey at the Minnesota State Fair in August and September 2015 addressing knowledge regarding the pathogenesis of atopic dermatitis (AD), basic skin care practices, and the perceived role of infection and food allergies in AD. Of participating parents, 82% identified food allergy or sensitivity in AD pathogenesis, whereas only 42% identified bacterial infection as an important factor in AD severity. Participants most often received education on skin health from their pediatrician (49%), followed by Internet-based sources (23%), rather than a dermatologist or pediatric dermatologist. Parents of children with AD overestimate the role of food allergies in this condition and are not as aware of the role of bacterial infection. Future educational directions from our specialty should focus on resources for pediatricians and families that emphasize these factors.


[Porokeratosis in a patient with dermatomyositis].
There are several reports of porokeratosis in the context of immmunosuppressive diseases. These mainly include organ transplant, HIV infection, lymphomas and some inflammatory and autoimmune diseases commonly treated with immunosuppresive drugs or chemotherapy. Disseminated superficial actinic porokeratosis is the clinical variant of porokeratosis that most frequently develops in immunosuppressive states. We report a case of porokeratosis in a woman with dermatomyositis.


Axillary Artery Injury Associated with Proximal Humerus Fracture: A Report of 6 Cases.
Proximal humerus fractures are common, but associated injury of the axillary artery is uncommon. The majority of published blunt traumatic axillary artery injuries are associated with anterior glenohumeral dislocation; a few are associated with isolated proximal humerus fractures or fracture-dislocation. Experience within our institution demonstrates that axillary artery injury is often unrecognized on initial presentation owing to palpable peripheral pulses and the absence of ischemia and places the hand at risk of necrosis and amputation if there is prolonged ischemia and the forearm at risk of compartment syndrome after revascularization. Accurate physical examination in combination with a low threshold for Doppler examination or angiography can establish the diagnosis of axillary artery injury. We present 6 cases of axillary artery injury associated with proximal humerus fractures in order to highlight the potential for this vascular injury in the setting of a proximal humerus fracture.


A field-evolved differential filtration method for recovery of schistosome cercariae.
Modifications to Theron 's (1979) differential filtration technique are described which improve both sensitivity and reliability. Following pre-filtration to remove larger debris and some plankton, the sample is formalized; constant stirring prevents losses due to the cercarial stickiness normally caused by the fixation process. Once fixed, Schistosoma mansoni cercariae are reliably retained and well displayed on nylon monofilament cloth of 50 micrometers pore size. Such a coarse recovery filter permits very large samples to be processed and results in filters which are easy to read. Field comparison showed the method improved sensitivity by a factor of more than 20 times and laboratory evaluation indicated a recovery rate of over 80%.


Effect of short-term administration of cinnamon on blood pressure in patients with prediabetes and type 2 diabetes.
The aim of this study was to systematically review and evaluate the effect of short-term administration of cinnamon on blood pressure regulation in patients with prediabetes and type 2 diabetes by performing a meta-analysis of randomized, placebo-controlled clinical trials. Medical literature for randomized controlled trials (RCTs) of the effect of cinnamon on blood pressure was systematically searched; three original articles published between January 2000 and September 2012 were identified from the MEDLINE database and a hand search of the reference lists of the articles obtained through MEDLINE. The search terms included cinnamon or blood pressure or systolic blood pressure (SBP) or diastolic blood pressure (DBP) or diabetes. A random effects model was used to calculate weighted mean difference and 95% confidence intervals (CI). The pooled estimate of the effect of cinnamon intake on SBP and DBP demonstrated that the use of cinnamon significantly decreased SBP and DBP by 5.39 mm Hg (95% CI, -6.89 to -3.89) and 2.6 mm Hg (95% CI, -4.53 to -0.66) respectively. Consumption of cinnamon (short term) is associated with a notable reduction in SBP and DBP. Although cinnamon shows hopeful effects on BP-lowering potential, it would be premature to recommend cinnamon for BP control because of the limited number of studies available. Thus, undoubtedly a long-term, adequately powered RCT involving a larger number of patients is needed to appraise the clinical potential of cinnamon on BP control among patients with type 2 diabetes mellitus.


Detection of T- and B-cell Target Antigens of Fowlpox Virus Isolated from Backyard Chickens in India.
With the aim of assessing the antigenic characteristics of a circulating pool of fowlpox virus (FPV) that exists in the backyard poultry system in India, one of the field isolates generated was characterized by in vitro immunologic techniques. FPV was isolated from clinically positive fowlpox cases (n = 10) from the Jhargram (West Midnapur district) and Kakdwip (South 24 Pargana district) areas of West Bengal State, India. Initially, FPV-specific PCR was performed for confirmation of the samples. Isolation of FPV was done using embryonated chicken eggs and the choreoallantoic membrane route. Subsequently, FPV antigen was prepared from chicken embryo fibroblast cell culture-adapted field isolate. Biologic transmission of FPV was performed in Rhode Island red chickens experimentally to assess humoral and cell-mediated immune (CMI) responses. High level of anti-FPV antibodies were observed in test birds as assessed by indirect ELISA. Seroreactive polypeptides (B-cell antigens) of FPV antigen with molecular weights of 44.5, 66.5, 75, 90.5, and 99 kDa were detected by western blot analysis. Significant increases in CMI responses were observed in inoculated chickens as assessed by lymphocyte proliferation assay, cytotoxicity assay, and T-cell immunoblotting. The predominant T-cell antigen of FPV detected had a molecular weight of 66.5 kDa. The present study revealed the antigenic characteristics of FPV that exists in backyard poultry system in West Bengal for the first time, thus exploring the rationality of designing future T- and B-cell vaccines against fowlpox.


Diagnostic Utility of Whole Exome Sequencing in the Neuromuscular Clinic.
Next-generation sequencing is a powerful diagnostic tool, yet it has proven inadequate to establish a diagnosis in all cases of congenital hypotonia or childhood onset weakness. We sought to describe the impact of whole exome sequencing (WES), which has only recently become widely available clinically, on molecular diagnosis in the Nationwide Children's Hospital Neuromuscular clinics. We reviewed records of all patients in our clinic with pediatric onset of symptoms who had WES done since 2013. Patients were included if clinical suspicion was high for a neuromuscular disease. Clinical WES was performed in 30 families, representing 31 patients, all of whom were seen for hypotonia, weakness, or gait disturbance. Probands had between 2 and 12 genetic diagnostic tests prior to obtaining WES. A genetic diagnosis was established in 11 families (37%), and in 12 patients (39%), with mutations in 10 different genes. Five of these genes have only been associated with disease since 2013, and were not previously represented on clinically available disease gene panels. Our results confirm the utility of WES in the clinical setting, particularly for genetically heterogeneous syndromes. The availability of WES can provide an end to the diagnostic odyssey for parents and allow for expansion of phenotypes.


Nurses' Perceptions of Quality Care.
Limited research has been conducted on how nurses define or perceive "quality nursing care." We conducted focus groups to identify nurses' perceptions of quality care at a Midwestern academic medical center. Transcripts of the focus group sessions were analyzed using thematic analysis techniques, and 11 themes emerged: Leadership, Staffing, Resources, Timeliness, Effective Communication/Collaboration, Professionalism, Relationship-Based Care, Environment/Culture, Simplicity, Outcomes, and Patient Experience.


Urinary neopterin and total neopterin measurements allow monitoring of oxidative stress and inflammation levels of knee and hip arthroplasty patients.
Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation. Urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) levels were analysed in 28 knee and 22 hip arthroplasty patients pre- and post-operatively to determine oxidative stress and inflammation levels. Total neopterin was 31.1% higher with knee arthroplasty (p<0.05). Urinary neopterin was 32.8% higher in the knee arthroplasty group versus hips. The increase in neopterin and total neopterin following a post-surgical decrease in levels was significant in both groups. Levels of neopterin and total neopterin were varied between patients, but all increased following surgery and subsided by day 28. The increased levels of urinary neopterin and total neopterin from knee arthroplasty indicate that knee osteoarthritis and arthroplasty is a more significant trauma to the body than hip osteoarthritis and arthroplasty surgery. This is also shown by faster inflammatory resolution following hip arthroplasty.


Pregnancy and Neonatal Outcomes in Gestational Diabetes Treated with Regular Insulin or Fast-Acting Insulin Analogues.
Fast-acting insulin analogues (FAIAs) are being used more frequently during pregnancy. Previous studies comparing regular insulin (RI) and FAIA consist primarily of women enrolled with pre-existing diabetes; therefore, we compared pregnancy and neonatal outcomes in women with gestational diabetes. We retrospectively investigated 197 pregnant women with gestational diabetes mellitus (GDM) requiring insulin treatment for glycemic control. Individuals were divided into 2 groups: RI (n = 55) and FAIA (aspart or lispro; n = 142). Pregnancy outcomes, including caesarean section rate, and neonatal outcomes, including macrosomia and ponderal index, were compared between groups. There were no significant differences in maternal baseline characteristics (age, parity, body mass index and weight gain) between groups or in haemoglobinA1c before delivery. The frequency of emergency caesarean section (caesarean section after trial of labor) was not significantly different between groups (RI 16.7%, FAIA 24.7%; p = 0.452). There were no differences in frequencies of macrosomia (RI 3.4%, FAIA 6.5%; p = 0.518), ponderal index (RI 2.65 ± 0.5, FAIA 2.71 ± 0.5; p = 0.322), cranial-thoracic circumference ratio (RI 1.07 ± 0.06, FAIA 1.07 ± 0.06; p = 0.386) or neonatal hypoglycemia (RI 5.1%, FAIA 5.8%; p = 1.000). Our data indicate that FAIA achieves similar pregnancy and neonatal outcomes in GDM compared with RI. Considering patient convenience, FAIA may be better to use during pregnancy.


Sleep-Wake Concordance in Couples Is Inversely Associated With Cardiovascular Disease Risk Markers.
To determine whether interdependence in couples' sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night) is associated with two markers of cardiovascular disease (CVD) risk, ambulatory blood pressure (BP) and systemic inflammation. This community-based study is a cross-sectional analysis of 46 adult couples, aged 18-45 years, without known sleep disorders. Percent sleep-wake concordance, the independent variable, was calculated for each individual using actigraphy. Ambulatory BP monitors measured BP across 48 h. Dependent variables included mean sleep systolic BP (SBP) and diastolic BP (DBP), mean wake SBP and DBP, sleep-wake SBP and DBP ratios, and C-reactive protein (CRP). Mixed models were used and were adjusted for age, sex, education, race, and body mass index. Higher sleep-wake concordance was associated with lower sleep SBP (b = -.35, SE = .01) and DBP (b = -.22, SE = .10) and lower wake SBP (b = -.26, SE = .12; all p values < .05). Results were moderated by sex; for women, high concordance was associated with lower BP. Men and women with higher sleep-wake concordance also had lower CRP values (b = -.15, SE = .03, p < .05). Sleep-wake concordance was not associated with wake DBP or sleep/wake BP ratios. Significant findings remained after controlling for individual sleep quality, duration, and wake after sleep onset. Sleep-wake concordance was associated with sleep BP, and this association was stronger for women. Higher sleep-wake concordance was associated with lower systemic inflammation for men and women. Sleep-wake concordance may be a novel mechanism by which marital relationships are associated with long-term CVD outcomes.


ISOLATION OF Cryptococcus neoformans FROM ENVIRONMENTAL SAMPLES COLLECTED IN SOUTHEASTERN NIGERIA.
Cryptococcosis caused by Cryptococcus neoformans is the second most common fungal opportunistic pathogen and a life-threatening infection with serious clinical manifestations especially in HIV/AIDS and other immunocompromised patients. In Nigeria, HIV/AIDS infection has reached an alarming level. Despite this, information on the presence of this fungus in clinical and environmental samples is very scanty in Nigeria and many other parts of Africa. We set out to evaluate the presence of Cryptococcus neoformans or C. gattiiin pigeon droppings obtained from Southeastern Nigeria. One hundred and seventy-seven samples of pigeon droppings from six sample types were collected. The area covered comprised of ten cities and other locations spanning across five States in Nigeria. Using established techniques, Cryptococcus neoformans was isolated from 39 of the 177 (22.0%) samples overall. No C. gattiiwas isolated. Most of the isolates (32.4%) were recovered from dovecotes (11 of 34) followed closely by samples taken from markets (31.8%; seven of 22) and least from the church (4.0%; one of 25). The highest isolation rate (38.9%) was found in samples from Enugu-Ezike(seven of 23) while the least came from Afikpo and the other locations each with 9.1% isolation rate. This is the first large-scale screening of Cryptococcus neoformans from pigeon droppings in Nigeria. The ecological and epidemiological significance of these findings are discussed.


Achieving primary closure and enhancing aesthetics with periodontal microsurgery.
The continuous search for improved surgical procedures to address gingival deformities is a consequence of an increasing demand for aesthetics in the periodontal clinical practice. Innovative techniques have been reported to help clinicians achieve predictability in root coverage. Significant progress can be attributed to the inclusion of the operative microscope in periodontal therapy, particularly in regards to obtaining primary closure. This article describes a microsurgical technique used to treat gingival recessions, showing its potential for obtaining optimal aesthetic results.


[Laboratory medicine, my philosophy and prospect].
I have been working in the field of laboratory medicine for 45 years including the period of working as a physician. During my career, some of my dreams in laboratory diagnosis have been realized, and some have not. Although the issues changed with time, our basic philosophy has not changed at all. In this session, I would like to discuss "my philosophy of laboratory medicine", that is, what I have intended and what I have done. First, I describe the role of laboratory medicine in the field of clinical medicine. Second, I discuss the value of laboratory tests especially for clinical diagnostics. Third, I summarize the history of clinical pathology with reflection of the past, and my anticipation for the future. Fourth, I mention about the task and responsibility of the laboratory technicians and clinical pathologists, in view of their common purpose, clinical diagnosis. Finally, I discuss the future aspect of laboratory medicine.


Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia.
Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.


Medical treatment of symptomatic endometriosis.
The concept of endometriosis and strategies for its treatment are reviewed. Treatment is mainly endocrine-based, using progestogens, danazol and luteinizing hormone-releasing hormone (LHRH) agonists. Such treatment is complex, and therapy strategies have to be tailored to the individual; the choice of treatment, therefore, depends on the metabolic and side-effects of each compound.


Selective determination of nitrite in water and food samples using zirconium oxide (ZrO2)@MWCNTs modified screen printed electrode.
Nitrite ions are being used in different forms as food preservatives acting as flavor enhancers or coloring agents for food products. However, continuous ingestion of nitrite may have severe health implications due to its mutagenic and carcinogenic effects. Thus, this study constructed an electrochemical assay using disposable nano-sensor chip ZrO2@MWCNTs screen printed electrodes (SPE) for the rapid, selective, and sensitive determination of nitrite in food and water samples. As a sensing platform, the use of nanomaterials, including metal oxide nanostructures and carbon nanotubes, exhibited a superior electrocatalytic activity and conductivity. Morphological, structural, and electrochemical analyses were performed using electron microscopy (SEM and TEM), Fourier-transform infrared (FTIR) spectroscopy, electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and chronoamperometry (CA). Accordingly, a wide dynamic linear range (5.0 μM to 100 μM) was obtained with a limit of detection of 0.94 μM by the chronoamperometric technique. In addition, the sensor's selectivity was tested when several non-target species were exposed to the sensor chips while no obvious electrochemical signals were generated when the nitrite ions were not present. Eventually, real food and water sample analysis was conducted, and a high recovery was achieved.


Clinical assessment of non carious cervical lesion using swept-source optical coherence tomography.
Non-carious cervical lesions (NCCLs) involve various forms of tooth loss with different etiologies. This study aimed to utilize swept-source optical coherence tomography (SS-OCT) at 1300 nm wavelength range in vitro and in vivo to evaluate and clarify the mechanism of NCCLs. In the in vitro phase, a dentin attenuation coefficient (μt ) derived from the SS-OCT signal at NCCL was compared with mineral loss obtained from transverse microradiography (TMR) to determine a μt threshold to discriminate demineralization of cervical dentin in vivo. In the clinical study, 242 buccal surfaces were investigated in 35 subjects. Presence and dimensions of NCCLs, cervical cracking and the degree of demineralization at the exposed cervical dentin were determined using SS-OCT. Dentin demineralization was observed in 69% of NCCLs. SS-OCT results confirm that dentin mineral loss and occlusal attrition were associated with larger NCCLs, and can be considered as an etiological factor in formation and progress of these lesions. (A) We determined the attenuation coeffcient (μt ) threshold of SS-OCT signal for the detection of demineralization (1.21) from in vitro study. DEM: demineralized dentin, sound: sound dentin. (B) Using the μt threshold, we observed NCCLs in vivo to detect the demineralization in cervical dentin. SS-OCT scanning was performed along the red line. (C) SS-OCT image obtained along the red line in B. In SS-OCT, brightness of dentin beneath the NCCL was increased (arrow) compared with intact zone. The cervical dentin was slightly demineralized (μt : 1.25). e: enamel, d: dentin, g: gingiva.


Apparent successful mesothelial cell transplantation hampered by peritoneal activation.
Mesothelial cell transplantation has been suggested to improve mesothelial repair after surgery, recurrent peritonitis and peritoneal dialysis. In this study we evaluated mesothelial cell transplantation during the resolution phase of experimentally thioglycollate-induced peritonitis in rats. To this end 4 x 10(6) DiO-labeled autologous mesothelial cells were transplanted 1 week after peritonitis induction. Peritoneal inflammation and permeability characteristics were evaluated after another week. Mesothelial cell transplantation after peritonitis resulted in incorporation of these cells in the parietal mesothelial lining, leading to an acute transient submesothelial thickening which was not seen in transplanted animals without prior peritonitis induction. Long-term functioning of these repopulated mesothelial cells leaded to peritoneal activation as evidenced by a approximately twofold increase in peritoneal lymphocytes (P < 0.01) and omental mast cell counts (P < 0.05), accompanied by the induction of inflammation markers monocyte chemoattractant protein-1 (MCP-1) (P < 0.01) and hyaluronan (P < 0.01) in the transplanted peritonitis group, but not in rats with peritonitis without mesothelial cell transplantation or in control rats without mesothelial cell transplantation (all four parameters P < 0.01). In addition, trapping of transplanted mesothelial cells in the milky spots of omental tissue and lymphatic stomata of the diaphragm both in control and thioglycollate rats seems to increase microvascular permeability, reflected by apparent increased diffusion rates of small solutes and proteins. Altogether, our data underscore the importance of controlling peritoneal (patho)physiology and function in mesothelial transplantation protocols.


Short-term use of Lacticaseibacillus rhamnosus SD11 and the oral microbiome: Low caries RCT study.
The objective of the study was to investigate the effect of short-term lozenges containing Lacticaseibacillus rhamnosus SD11 on cariogenic pathogens and on oral microbiota. This double-blind, randomized, controlled trial included 121 subjects and was randomly divided into the control and probiotic group. All subjects were blindly administered to receive the control- or probiotic L. rhamnosus SD11 lozenges every day for 4 weeks and then followed up for another 4 weeks. After probiotic consumption, the probiotic group had significantly lower levels of Streptococcus mutans and significantly higher levels of total lactobacilli at 4 and 8 weeks compared with the baseline. The 16S rRNA sequencing revealed an increase in bacterial diversity and beneficial bacteria in the Firmicutes phylum, Bacilli class, and a reduction in the mutans streptococci group in the probiotic group. The opposite results were found in the control group. This study did not find any caries increment, nor did the subjects have any side effects after product consumption. With the limitation of a short-time study in low caries children, it showed that L. rhamnosus SD11 could increase beneficial bacteria in the Firmicutes phylum and Bacilli class that might support good oral health in children.


Effect of soy flour on nutritional, physicochemical, and sensory characteristics of gluten-free bread.
The aim of this study was to assess the effect of soy flour on nutritional, physicochemical, and sensory characteristics of gluten-free (GF) bread. In this study, corn flour was replaced with soy flour at different levels 5%, 10%, and 15% to produce a more nutritionally balanced GF bread. Physical and chemical properties, sensory evaluation and crust and crumb color were measured in bread samples. The results of evaluations showed that protein content of soy flour-supplemented GF bread significantly increased from 9.8% to 12.9% as compared to control along with an increased in fat (3.3%-4.1%), fiber (0.29%- 0.38%), and ash (1.7%-2.2%) content. Moisture (27.9%-26.5%) and carbohydrate (58.3-52.3) content decreased with the incremental addition of soybean flour. The highest total score of sensory evaluation was for the bread sample containing 15% soybean flour. The evaluation of crust and crumb showed that bread samples with 15% soy flour were significantly darker than the other bread samples. In conclusion, adding higher levels of soybean flour into GF bread can improve bread quality, sensory characteristics, and nutritional properties of bread. Nutritional status in patients with celiac disease (CD) can be improved through the produce GF bread in this way.


Thyroid hormone does not induce maturation of embryonic chicken cardiomyocytes in vitro.
Fetal cardiac growth in mammalian models occurs primarily by cell proliferation (hyperplasia). However, most cardiomyocytes lose the ability to proliferate close to term and heart growth continues by increasing cell size (hypertrophy). In mammals, the thyroid hormone triiodothyronine (T3) is an important driver of this process. Chicken cardiomyocytes, however, keep their proliferating ability long after hatching but little information is available on the mechanisms controlling cell growth and myocyte maturation in the chicken heart. Our aim was to study the role of T3 on proliferation and differentiation of embryonic chicken cardiomyocytes (ECCM), enzymatically isolated from 19-day-old embryos and to compare the effects to those of insulin-like growth factor-1 (IGF-1) and phenylephrine (PE). Hyperplasia was measured using a proliferation assay (MTS) and hypertrophy/multinucleation was analyzed morphologically by phalloidin staining of F-actin and nuclear staining with DAPI. We show that IGF-1 induces a significant increase in ECCM proliferation (30%) which is absent with T3 and PE. PE induced both hypertrophy (61%) and multinucleation (41%) but IGF-1 or T3 did not. In conclusion, we show that T3 does not induce maturation or proliferation of cardiomyocytes, while IGF-1 induces cardiomyocyte proliferation and PE induces maturation of cardiomyocytes.


Treading Water: Tire Wear Particle Leachate Recreates an Urban Runoff Mortality Syndrome in Coho but Not Chum Salmon.
Tire tread wear particles (TWP) are increasingly recognized as a global pollutant of surface waters, but their impact on biota in receiving waters is rarely addressed. In the developed U.S. Pacific Northwest, acute mortality of adult coho salmon (Oncorhynchus kisutch) follows rain events and is correlated with roadway density. Roadway runoff experimentally triggers behavioral symptoms and associated changes in blood indicative of cardiorespiratory distress prior to death. Closely related chum salmon (O. keta) lack an equivalent response. Acute mortality of juvenile coho was recently experimentally linked to a transformation product of a tire-derived chemical. We evaluated whether TWP leachate is sufficient to trigger the acute mortality syndrome in adult coho salmon. We characterized the acute response of adult coho and chum salmon to TWP leachate (survival, behavior, blood physiology) and compared it with that caused by roadway runoff. TWP leachate was acutely lethal to coho at concentrations similar to roadway runoff, with the same behaviors and blood parameters impacted. As with runoff, chum salmon appeared insensitive to TWP leachate at concentrations lethal to coho. Our results confirm that environmentally relevant TWP exposures cause acute mortalities of a keystone aquatic species.


[Cloning and characterization of a monoterpene synthase gene from Tripterygium wilfordii].
Tripterygium wilfordii is a medicinal plant commonly used in the treatment of rheumatoid arthritis,and with pharmacological activities in anti-tumor and obesity treatment. The known active ingredients in T. wilfordii are mainly terpenoids,but with very low content. Therefore,the analysis of the biosynthesis pathway of terpenoids in T. wilfordii has become a research hotspot to solve the problem of its resources. Terpenoid synthase( TPS) is a key enzyme that catalyzes the formation of a wide variety of terpenoid skeletons. In this study,a gene fragment with an ORF of 1 785 bp was cloned from T. wilfordii. Bioinformatics analysis was performed using NCBI's BLASTP,ProtParam and Interpro online tools and MEGA 6.0 software. The response of this gene to methyl jasmonate was also detected by real-time fluorescent quantitative PCR,and its catalytic function was verified by prokaryotic expression and in vitro enzymatic assay. Bioinformatics analysis indicated that the amino acid sequence encoded by this gene had both N-terminal domain and C-terminal domain of TPS,as well as the DDxx D conserved domain of the class I of TPS family. And Tw MTS gathered together with TPS-b subfamily in the Neighbor-Joining Tree constructed with known homologous TPSs. The results of RT-PCR showed that 50 μmol·L-1 MeJA 12 h could increase the expression of Tw MTS to 735 times in the control group at 12 h,and 1 644 times at 24 h. In addition,in vitro enzymatic reaction results showed that Tw MTS can catalyze the production of β-citronellol with GPP as substrate,indicating that Tw MTS was a monoterpene synthase. The above results provided a new element for the synthetic biology database of T. wilfordii terpenoids,and laid the foundation for future biosynthesis research.


Simulation of the Velocity and Temperature Distribution of Inhalation Thermal Injury in a Human Upper Airway Model by Application of Computational Fluid Dynamics.
Inhalation injury is an important cause of death after thermal burns. This study was designed to simulate the velocity and temperature distribution of inhalation thermal injury in the upper airway in humans using computational fluid dynamics. Cervical computed tomography images of three Chinese adults were imported to Mimics software to produce three-dimensional models. After grids were established and boundary conditions were defined, the simulation time was set at 1 minute and the gas temperature was set to 80 to 320°C using ANSYS software (ANSYS, Canonsburg, PA) to simulate the velocity and temperature distribution of inhalation thermal injury. Cross-sections were cut at 2-mm intervals, and maximum airway temperature and velocity were recorded for each cross-section. The maximum velocity peaked in the lower part of the nasal cavity and then decreased with air flow. The velocities in the epiglottis and glottis were higher than those in the surrounding areas. Further, the maximum airway temperature decreased from the nasal cavity to the trachea. Computational fluid dynamics technology can be used to simulate the velocity and temperature distribution of inhaled heated air.


Doxycycline and tissue repair in rats.
Iterations in collagen turnover are integral to tissue repair. Repair gone awry, as a result of excess collagen accumulation or degradation, can contribute to pathologic ventricular remodeling. Pharmacologic interventions that would attenuate either aspect of faulty repair have therefore attracted interest. Tetracyclines, which inhibit both collagen synthesis and degradation, as well as angiogenesis, may hold promise, unrelated to their antimicrobial properties, in this regard. Assessment of their potential in rodent hearts with experimental injury can be problematic, given the often microscopic nature of tissue repair and brief involvement of matrix metalloproteinases (MMPs). We therefore selected a subcutaneous model in which granulation and fibrous tissues form over several weeks in response to croton oil and where fibrous tissue is subsequently resorbed because of high levels of collagenolytic activity. Untreated rats were compared with those given daily oral doxycycline (40 mg/kg). We harvested pouch tissue and exudate weekly for 5 weeks to assess hydroxyproline concentration and MMP activity (gelatin substrate zymography) of pouch wall and mononuclear cell count of pouch exudate. At week 2, neovascularization in pouch wall was measured by means of intravenous infusion of carmine-red dye in gelatin. The resultant "vascular cast" was solubilized and dye content quantitated with the use of spectrophotometry. Serum was assayed weekly for type I collagen carboxyterminal telopeptide (ICTP), a marker of collagen degradation. During weeks 1 and 2 and compared with untreated controls, doxycycline-treated rats had attenuated pouch tissue weight, collagen concentration, MMP2 lytic activity and vascularity, and reduced exudate volume and mononuclear cells. In vitro, doxycycline inhibited tissue gelatinolytic activity in a dose-dependent manner. At weeks 4 and 5, pouches were larger and collagen concentration was higher in doxycycline-treated rats, and serum ICTP levels were reduced at weeks 3 and 4. During the initial phase of pouch development, doxycycline exerts an inhibitory effect on tissue formation, likely mediated through its attenuation of angiogenesis and modulations of collagen turnover. As repair proceeds in subsequent weeks, doxycycline retards collagen degradation and pouch resorption by inhibiting MMPs. Doxycycline offers a multifaceted pharmacologic profile with which to modify various aspects of tissue repair in the rat.


Notes on the development of metacercaria and adult of Echinostoma porteri Fashuyi (Echinostomatidae).
The metacercaria of E. porteri was found to retain its viability for a longer time in Bulinus (Physopsis) globosus (Morelet) than in Bulinus (Bulinus) forskalii (Ehrenberg) and Lymnaea natalensis (Krauss) which is the natural host for other larval stages. It becomes infective to definitive hosts about 6 h after commencement of encystment and loses its viability after 14 days in the snail host. Development of adult takes place experimentally in chicks, pigeons and rats, but hosts show age resistance to infection. Growth of adult worm is most rapid between 4th and 6th day and declines after the 17th day. Proportionate increase in body length is higher than similar increases in size of other parts of the body.


[Systemic antifungal agents].
Invasive fungal infection is the infectious complication with highest associated mortality. Until the 90's amphotericin B was the only drug available to treat these infections. Its spectrum of antifungal activity is excellent, but its use is associated with toxicity in many cases. The development of amphotericin B lipid formulations has resulted in a significant decrease in most of the side effects associated with this drug. Triazoles are safe and effective for treating most invasive fungal infections. Fluconazole is an excellent drug for the prevention and treatment of Candida and Cryptococcus infections, itraconazole has good activity against Candida and Aspergillus, and voriconazole has shown to be better than amphotericin B for invasive aspergillosis. Caspofungin belongs to a new group of antifungal agents, the echinocandins, which are very safe and present excellent activity against Candida and Aspergillus.


Asymmetric total syntheses of two phlegmarine-type alkaloids, lycoposerramines-V and -W, newly isolated from Lycopodium serratum.
Two new Phlegmarine-type alkaloids, lycoposerramines-V and -W, were isolated from Lycopodium serratum, and their structures including the absolute configuration were established by asymmetric total synthesis involving such key steps as Johnson-Claisen rearrangement, asymmetric allylation, and ring-closing metathesis (RCM)- or SmI(2)-mediated stereoselective piperidine ring construction.


Avian flu from an occupational health perspective.
Although a pandemic scenario necessarily involves a situation in which a large number of people become infected in a nonoccupational setting, past infectious disease events have highlighted the unique role that occupational exposure may play in the emergence of disease in humans. While small-scale poultry farmers have already demonstrated their high risk of exposure and subsequent infection with H5N1 avian flu, other bird handling occupations may also be at high risk. In this review article, the author highlights the occupational health aspects of a newly emerging infectious disease, H5N1 avian flu, and the efforts being made by various authorities to confront the possibility of the next flu pandemic. Various measures potentially available to protect high-risk workers are outlined, emphasizing a hierarchy of controls in which these measures can be placed. The author postulates that, by reducing the risk of transmission of avian flu to these workers, occupational medicine can play a pivotal role in the world's effort to prepare for a pandemic, and may be uniquely positioned to contribute to the effort to delay or even avert the emergence of the next pandemic.


The role of the surgeon in the evolution of flexible endoscopy.
Several cultures, including the Egyptians, Greeks, Romans, and Arabs, made attempts to view accessible human body cavities using a variety of instruments such as spatulas and specula. The first endoscope was created in 1806 when Phillip Bozzini, a German-born urologist, constructed the lichtleiter, which used concave mirrors to reflect candlelight through an open tube into the esophagus, bladder, or rectum. Maximilian Carl-Friedrich Nitze, another German urologist, produced the first usable cystoscope in 1877 by using series of lenses to increase magnification. He was also the first to place light inside the organ of interest to aid visualization. In 1880 Mikulicz made the first gastroscope using a system similar to Nitze's cystoscope. Modern endoscopy was born with the introduction of the fiberoptic endoscope in the late 1950s. Over the ensuing 50 years endoscopy revolutionized many aspects of the surgeon's practice. Endoscopy can now be used to diagnose and often treat gastrointestinal cancer, hemorrhage, obstruction, and inflammatory conditions. This review was initiated by the SAGES Flexible Endoscopy Committee to chronicle the role of the surgeon in the development and introduction of flexible endoscopy into clinical practice, historically and in contemporary surgery. Flexible endoscopy evolved out of surgeons' need to overcome diagnostic and therapeutic challenges. There have been many recent technological advances that facilitate endoluminal therapies, and flexible endoscopy is now traversing new ground. Surgeons have been major contributors in the development of all aspects of endoscopy. There is a continually expanding list of therapeutic options available to patients. The difficult questions of which procedure, on which patient, and when can be answered best by the surgeon versed in endoscopic, laparoscopic, and open surgical techniques.


EVALUATION OF EYE LENS DOSE TO WORKERS IN THE STEAM GENERATOR AT THE KOREAN OPTIMIZED POWER REACTOR 1000.
ICRP (2011) revised the dose limit to the eye lens to 20 mSv/y based on a recent epidemiological study of radiation-induced cataracts. Maintenance of steam generators at nuclear power plants is one of the highest radiation-associated tasks within a non-uniform radiation field. This study aims to evaluate eye lens doses in the steam generators of the Korean OPR1000 design. The source term was characterized based on the CRUD-specific activity, and both the eye lens dose and organ dose were simulated using MCNP6 combined with an ICRP voxel phantom and a mesh phantom, respectively. The eye lens dose was determined to be 5.39E-02-9.43E-02 Sv/h, with a negligible effect by beta particles. As the effective dose was found to be 0.81-1.21 times the lens equivalent dose depending on the phantom angles, the former can be used to estimate the lens dose in the SG of the OPR1000 for radiation monitoring purposes.


The influence of packed cell volume versus plasma proteins on thromboelastographic variables in canine blood.
Determine the correlation between kaolin-activated thromboelastography (TEG) variables (R, K, angle, and maximum amplitude [MA]) and PCV, fibrinogen concentration (FC), and total fibrinogen (TF) in an ex vivo model. Two healthy adult mixed-breed dogs. Citrated whole blood was obtained and separated into packed red cells, platelet rich plasma, and platelet poor plasma (PPP). An aliquot of PPP was heated to denature heat labile proteins (fibrinogen, factor V, factor VIII). Blood components were recombined for analyses of 6 physiological scenarios: anemia with low fibrinogen; anemia with moderate fibrinogen; anemia with normal fibrinogen; anemia with normal saline; normal PCV and normal fibrinogen; and normal PCV and low fibrinogen. A Kruskal-Wallis test, along with linear regressions on pairwise combinations of TEG variables, was used to determine the correlation between TEG variables and PCV, FC, and TF. Maximum amplitude correlated with FC (R2 0.60, P < 0.001) and TF (R2 0.57, P < 0.001) but not PCV (R2 0.003, P = 0.7). Angle and K time were moderately correlated with FC ([angle: R2 0.53, P < 0.001]; [K: R2 0.55, P < 0.001]) and TF ([alpha angle: R2 0.52, P < 0.001]; [K: R2 0.51, P < 0.001]) but not PCV. The R time was weakly correlated with PCV (R2 0.15, P < 0.009) but not FC or TF. In an ex vivo model, plasma proteins but not PCV impacted TEG variables. This suggests that TEG changes noted with anemia are imparted by changes in available fibrinogen in a fixed microenvironment rather than artifact of anemia.


Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.
Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.


Variations in positron emission tomography-computed tomography findings for patients receiving neoadjuvant and non-neoadjuvant therapy for non-small cell lung cancer.
The aims of this study were to predict locoregional lymph node (LN) metastases using positron emission tomography-computed tomography (PET-CT) and investigate variations in PET-CT findings for patients receiving neoadjuvant (NT) and non-neoadjuvant (non-NT) for non-small cell lung cancer (NSCLC). Data from 578 consecutive patients from January 2010 to December 2015 who met this study inclusion criteria were retrospectively reviewed. All patients underwent curative and complete resections for NSCLC in a Korean hospital. We analyzed the associations between maximum standard uptake value (SUVmax) and pathological stage, compared disease-free survival (DFS) and overall survival (OS), investigated relationships among SUVmax values, evaluated LN status and compared pathologically negative and positive LNs by SUVmax, and assessed the influence of neoadjuvant therapy on SUVmax. All LNs were analyzed separately for N1 and N2. (I) For non-NT, we found significantly positive associations between pathological stage and SUVmax (tumor, N1 LN, and N2 LN, all P<0.001). For NT, we found positive correlations between pathological stage and tumor and N2 LN SUVmax, except for N1 LN (tumor P=0.005, N1 LN P=0.981, N2 LN P=0.045); (II) for non-NT, the low SUVmax group had higher DFS and OS than the high SUVmax group (DFS: tumor SUVmax P<0.001, N1 LN SUVmax P=0.002, N2 LN SUVmax P=0.027; OS: tumor SUVmax P<0.001, N1 LN SUVmax P=0.006, N2 LN SUVmax P=0.006). For NT, the low SUVmax group had nonsignificantly higher DFS and OS than the high SUVmax group. When age, sex, and SUVmax were equal, pathological stages were significantly higher for NT than non-NT (P<0.001). Non-NT had significantly higher DFS (P=0.001) and OS (P=0.024) than NT; (III) for non-NT, tumor, N1 LN, and N2 SUVmax were positively associated (all P<0.001). For NT, tumor and N2 SUVmax (P<0.001), and N1 and N2 SUVmax (P=0.025) correlated positively; tumor and N1 LN SUVmax did not (P=0.911); (IV) for non-NT, there was significant cutoff values for prediction of LN metastases using both tumor and LN SUVmax (N1 LN: tumor SUVmax cutoff 5.95, sensitivity 66.3%, specificity 66.0%, area =0.748, P<0.001; N1 LN SUVmax cutoff 2.05, sensitivity 57.83%, specificity 66.43%, area =0.676, P<0.001) (N2 LN: tumor SUVmax cutoff 5.95, sensitivity 63.04%, specificity 63.95%, area =0.726, P<0.001; N2 LN SUVmax cutoff 2.05, sensitivity 65.22%, specificity 69.96%, area =0.678, P<0.001). For NT, no SUVmax values significantly predicted LN metastases; () Pathologically malignant and benign LN SUVmax after neoadjuvant therapy were not different (N1 LN P=0.570, N2 LN P=0.105). For non-NT, pathologically malignant LN SUVmax was significantly higher than pathologically benign LN SUVmax (N1 LN P<0.001, N2 LN P=0.001). This study showed variations in PET-CT findings for NT and non-NT, which should be verified for evaluation and management, especially for surgery planning. SUV max is not a reliable predictor of lymphatic involvement after neoadjuvant therapy in patients with NSCLC. Surgery should not be withheld or delayed based on lack of knowledge about variations in PET-CT findings, which must be interpreted in conjunction with other conditions. Further studies on interpretation of PET-CT findings, especially for NT, are needed for better management and prognosis.


OsGCD1 is essential for rice fertility and required for embryo dorsal-ventral pattern formation and endosperm development.
Rice fertility is critical for rice reproduction and is thus a focus of interest. Most studies have addressed male sterility and its relation to rice production. The mechanisms of regulation of embryogenesis and endosperm development are essential for rice reproduction, but remain largely unknown. Here, we report a functional analysis of the rice gene OsGCD1, which encodes a highly conserved homolog of Arabidopsis GCD1 (GAMETE CELLS DEFECTIVE1). OsGCD1 mutants were generated using the CRISPR/Cas9 system and subjected to functional analysis. The homozygote mutants cannot be obtained, whereas heterozygotes showed altered phenotypes. In the majority of aborted seeds, the endosperm nucleus divided a limited number of times. The free nuclei were distributed only at the micropylar end of embryo sacs, and their oriented positioning was blocked. In addition, aleurone differentiation was interrupted. The embryo developed slowly, and pattern formation, particularly the dorsal-ventral pattern and symmetry establishment, of embryos was disturbed. Thus, the embryos showed various morphological and structural dysplasias. Our findings reveal that OsGCD1 is essential for rice fertility and is required for dorsal-ventral pattern formation and endosperm free nucleus positioning, suggesting a critical role in sexual reproduction of both monocotyledon and dicotyledon plants.


Relationship between dynamin 1 mutation status and characteristics of recurrent episodes of exercise-induced collapse in Labrador Retrievers.
To identify characteristics of exercise-induced collapse in Labrador Retrievers and compare characteristics for dogs with various dynamin 1 gene (DNM1) mutation statuses. Retrospective cross-sectional study. 109 Labrador Retrievers with a history of recurrent exercise-induced collapse, clinically normal behavior and gait between episodes, and no reason for collapse identified via medical evaluation. Data were collected via surveys from owners of dogs that were tested for an autosomal recessive DNM1 mutation causing DNM1-associated exercise-induced collapse (d-EIC). Dogs were identified as having d-EIC (homozygous for the mutation) or not having d-EIC (heterozygous for or without the mutation). Survey data were reviewed by an investigator unaware of the genotypes of dogs, and collapse characteristics were compared between groups. 74 dogs had d-EIC; 35 dogs did not have d-EIC. Dogs with d-EIC were young (median age, 12 months) at the time of the first collapse episode; collapse in such dogs typically originated in the hind limbs and was characterized by low muscle tone, clinically normal mentation, and rapid recovery. Dogs without d-EIC were older (median age, 23 months) than dogs with d-EIC; such dogs had various characteristics of collapse that were not consistent with a single disease. Characteristics of exercised-induced collapse in Labrador Retrievers with various DNM1 genotypes were identified in this study; findings may help distinguish dogs with d-EIC from those with other types of collapse conditions. Characteristics of collapse in Labrador Retrievers that were not homozygous for the DNM1 mutation differed substantially among dogs and may have been attributable to multiple causes.


Bladder cancer 2000: molecular markers for the diagnosis of transitional cell carcinoma.
The search continues for better tumor markers to improve the rate of detection of transitional cell carcinoma (TCC) more quickly in larger populations and to predict the possibility of disease recurrence. Among several new tests currently being screened, telomerase and hyaluronic acid/hyaluronidase (HA/HAase) have shown sensitivity and specificity equal to or better than cytology, and other promising tumor markers are being investigated. Although no marker has yet replaced the need to perform cystoscopy and cytology, the new tests can minimize the cost and difficulty of screening and long-term surveillance of patients who have or are at risk for bladder cancer.


Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis.
We postulated that the coagulopathy initiated by the inflammatory response to severe sepsis would be reflected by changes in the platelet count and prothrombin time that convey prognostic information. To examine this hypothesis, we looked at the utility of a simple evolving disseminated intravascular coagulation (DIC) score that awarded 1 point for each of the following: a) an absolute platelet count <100 x 10/L; b) a prothrombin time >15.0 secs; c) a 20% decrease in platelets; and d) a >0.3-sec increase in prothrombin time in predicting outcome in patients with severe sepsis. Prospective observational study. Intensive care units of university medical center. Patients were 163 critically ill severe sepsis patients. None. Patients were clinically classified as having capillary leak syndrome (n = 24), multiple organ failure with death from sepsis (n = 37), or multiple organ failure with recovery (n = 57) or as well (n = 45) if they showed rapid improvement in their modified Multiple Organ Dysfunction Syndrome (MODS) score (which did not score for thrombocytopenia). Patients with capillary leak syndrome had the highest Acute Physiology and Chronic Health Evaluation II score, modified MODS, and prothrombin time and the lowest platelet counts, whereas well patients had the most normal values. The simple evolving DIC score increased with worsening clinical class and was associated with worsening organ failure (increased modified MODS). Mortality rate increased from 10% for a simple evolving score of 0 to 73% for a score of 4 (p < .01). Overall, 86% of those with a score < or =1 survived, whereas 85% of those with a score of > or =2 developed multiple organ failure and half of them died from sepsis. The simple evolving DIC score calculated in the first 48 hrs from two readily available global coagulation markers appears to reflect the severity of the underlying disorder. It can be easily calculated at the bedside and provides useful prognostic information for the patient with severe sepsis.


CD4+CD25+FoxP3+ regulatory T cells and cytokines interact with estradiol in cases of missed abortion.
The aim of this study was to examine the interaction of estradiol (E2) with CD4+CD25+FoxP3+ regulatory T (Treg) cells and cytokines in cases of missed abortion (MA). The peripheral blood lymphocytes from patients with MA and controls (normal pregnancy and non-pregnant females) were isolated from the blood by Ficoll density gradient centrifugation. CD4+CD25+ Treg cells were isolated from peripheral blood mononuclear cells (PBMCs). The frequencies of CD4+CD25+FoxP3+ Treg cells and mRNA expression of transcription factor forkhead box protein 3 (FoxP3) in the peripheral blood of MA (n=33), normal pregnancy (n=33) and non-pregnant females (n=27) were determined by intracellular three-color flow cytometry and quantitative polymerase chain reaction (qPCR), respectively. The serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured by enzyme-linked immunosorbent assay (ELISA) and a chemiluminescent immunoassay was used to examine the serum E2 levels. It was observed that the percentage of Foxp3+ T cells in the peripheral blood of patients with MA were lower compared with those in the normal pregnancy and healthy non-pregnant controls. The results demonstrated that MA patients exhibited decreased levels of a peripheral Th2-related cytokine (IL-4) and E2. Furthermore, the low levels of CD4+CD25+Foxp3+ T cells and IL-4 correlated positively with serum concentrations of E2. The data indicated that maternal immunological changes may reverse maternal tolerance in MA, and this phenomenon may be due to the interaction of E2 with CD4+CD25+Foxp3+ T cells and cytokines in MA.


Prospective evaluation of 100 robotic-assisted unilateral adrenalectomies.
Our aim was to determine the learning curve for robotic adrenalectomy and factors that influence operative time and cost. We prospectively evaluated of 100 consecutive patients who underwent robotic, unilateral, transperitoneal adrenalectomy. The mean operative time for robotic-assisted adrenalectomy was 95 minutes and conversion rate was 5%. Pathology was aldosteronoma (n = 39), pheochromocytoma (n = 24), nonfunctional adenoma (n = 19), Cushing adenoma or hyperplasia (n = 16), and cyst (n = 2). Morbidity and mortality rates were 10% and 0%, respectively. The mean operative time decreased by 1 minute every 10 cases. Operative time improved more for junior surgeons than for senior surgeons (P = .006) after the first 50 cases. By multiple regression analysis, surgeon's experience (-18.9 +/- 5.5), first assistant level (-7.8 +/- 3.2), and tumor size (3 +/- 1.4) were independent predictors of operative time (P < .001 each). The robotic procedure was 2.3 times more costly than lateral transperitoneal laparoscopic adrenalectomy (euro4102 vs euro1799). Surgeon experience, resident training level, and tumor size are important variables for robotic-assisted, unilateral adrenalectomy and should be taken into account when this approach is evaluated. Controlled studies need to be performed to show potential relevant clinical benefits that could balance costs.


The Studies of Archaeological Pottery with the Use of Selected Analytical Techniques.
Modern analytical methods play an important role in archaeological objects, including ceramics. This review focuses on the use of analytical methods such as: gas chromatography coupled mass spectrometry, Fourier transform infrared spectroscopy, time-of-flight secondary ion mass spectrometry (ToF-SIMS), powder X-ray diffraction with thermal analysis to study the chemical and mineralogical composition of archaeological samples and organic residues preserved inside. In this paper, special attention was paid to the ToF-SIMS method, which allows the determination of characteristic ions on the surface of ceramic samples.


Chromosomal imbalances in laryngeal and hypopharyngeal cancers detected by comparative genomic hybridization.
The prognostic divergence of laryngeal and hypopharyngeal carcinomas is well known. Hypopharyngeal tumors are characterized by frequent metastasis formation and local recurrence, which is the source of the unfavorable prognosis of this subtype. The aim of this study was to define chromosomal alterations associated with the aggressive behavior of hypopharyngeal tumors. Twenty-nine head and neck squamous cell carcinomas (larynx n = 14 and hypopharynx n = 15) were analyzed by comparative genomic hybridization (CGH). Fluorescence in situ hybridization (FISH) was used to validate the CGH data and to compare the amplification pattern of the most frequently altered gene (cyclin-D1, CCND1) located on 11q13. The average number of genetic alterations was significantly higher in the hypopharyngeal tumors (P = 0.02). A good correlation of FISH and CGH data were seen. Gains on 11q13 were present in both subtypes, whereas amplification of CCND1 was associated with the aggressive phenotype by FISH. Chromosomal alteration, which was rarely detected in hypopharyngeal tumors but was observed in more than 50% of laryngeal carcinomas, was 8q gain. Our CGH and FISH data show that head and neck squamous cell carcinomas contain complex cytogenetic alterations and further support the hypothesis that different molecular pathways are responsible for the progression of differently localized tumors of the upper aerodigestive tract.


An unusual pleomorphic sarcoma in a hybrid mallard.
An unusual pleomorphic sarcoma from a hybrid mallard (Anas platyrhynchos) is described. Rhabdomyosarcoma was considered in the original differential diagnoses but rejected due to lack of specific characteristics generally seen in these tumors. The histologic characteristics described are consistent with mammalian sarcomas recorded in the literature as malignant fibrous histiocytoma.


Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free-living population of men and women.
The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. Caucasian men (n = 96) and women (n = 217) 20-29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. Among men, consumption of sucrose was 60 +/- 6, 48 +/- 4, and 39 +/- 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 +/- 4, 53 +/- 2, and 44 +/- 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption.


Lichen planopilaris-like eruption during treatment with tyrosine kinase inhibitor nilotinib.
Tyrosine kinase inhibitors are effective as a target therapy for malignant neoplasms. Imatinib was the first tyrosine kinase inhibitor used. After its introduction, several other drugs have appeared with a similar mechanism of action, but less prone to causing resistance. Even though these drugs are selective, their toxicity does not exclusively target cancer cells, and skin toxicity is the most common non-hematologic adverse effect. We report an eruption similar to lichen planopilaris that developed during therapy with nilotinib, a second generation tyrosine kinase inhibitor, in a patient with chronic myeloid leukemia resistant to imatinib. In a literature review, we found only one report of non-scarring alopecia due to the use of nilotinib.


Best hits of 11110110111: model-free selection and parameter-free sensitivity calculation of spaced seeds.
Spaced seeds, also named gapped q-grams, gapped k-mers, spaced q-grams, have been proven to be more sensitive than contiguous seeds (contiguous q-grams, contiguous k-mers) in nucleic and amino-acid sequences analysis. Initially proposed to detect sequence similarities and to anchor sequence alignments, spaced seeds have more recently been applied in several alignment-free related methods. Unfortunately, spaced seeds need to be initially designed. This task is known to be time-consuming due to the number of spaced seed candidates. Moreover, it can be altered by a set of arbitrary chosen parameters from the probabilistic alignment models used. In this general context, Dominant seeds have been introduced by Mak and Benson (Bioinformatics 25:302-308, 2009) on the Bernoulli model, in order to reduce the number of spaced seed candidates that are further processed in a parameter-free calculation of the sensitivity. We expand the scope of work of Mak and Benson on single and multiple seeds by considering the Hit Integration model of Chung and Park (BMC Bioinform 11:31, 2010), demonstrate that the same dominance definition can be applied, and that a parameter-free study can be performed without any significant additional cost. We also consider two new discrete models, namely the Heaviside and the Dirac models, where lossless seeds can be integrated. From a theoretical standpoint, we establish a generic framework on all the proposed models, by applying a counting semi-ring to quickly compute large polynomial coefficients needed by the dominance filter. From a practical standpoint, we confirm that dominant seeds reduce the set of, either single seeds to thoroughly analyse, or multiple seeds to store. Moreover, in http://bioinfo.cristal.univ-lille.fr/yass/iedera_dominance, we provide a full list of spaced seeds computed on the four aforementioned models, with one (continuous) parameter left free for each model, and with several (discrete) alignment lengths.


Lorazepam effects on Word Memory Test performance: a randomized, double-blind, placebo-controlled, crossover trial.
The Word Memory Test (WMT) is a common measure of symptom validity. To investigate the effects of acute benzodiazepines on WMT scores, oral lorazepam 2 mg (LOR) and placebo were administered 1 week apart in a randomized, double-blind, placebo-controlled, crossover study. A total of 28 participants completed the study and were administered the WMT during each drug condition. Within-participant comparisons of LOR vs placebo revealed significant LOR effects for Immediate Recognition (p = .007) and Consistency (p = .019), but not Delayed Recognition (p = .085). Significant LOR effects were present for Reaction Time Measures (Immediate Recognition RT, p = .013; Delayed Recognition RT, p = .001; Multiple Choice RT, p = .011) and Delayed Memory scores (Multiple Choice, p = .007; Paired Associates, p = .029; Free Recall, p = .001). A pattern similar to crossover results was detected for LOR vs placebo between-group differences for initial test assessment scores. When examined using publisher recommended cut scores for the principal WMT measures, there were six participants failing the WMT during initial LOR testing; all six subsequently performed in the normal range upon retesting with placebo. One participant failed WMT during placebo and obtained passing scores during LOR. These data indicate that multiple WMT measures may be affected by acute LOR dosing, and provide additional evidence that potential latent variables and their effects on both SVT performance and cognitive function should be part of the clinical decision-making process.


Profile differences in tetrodotoxin transfer to skin and liver in the pufferfish Takifugu rubripes.
Tetrodotoxin (TTX) was intramuscularly administered to nontoxic cultured specimens of the pufferfish Takifugu rubripes to investigate differences in the toxin transfer and accumulation profiles between the skin and liver. Test fish were administered TTX at doses of 30 (Low dose; LD), 100 (Medium dose; MD), and 300 (High dose; HD) μg/individual, respectively. Liquid chromatography/mass spectrometry analysis for TTX revealed that the TTX concentration in both the skin (0.48-1.7 μg/g) and liver (0.43-6.0 μg/g) at 24 h after the toxin administration increased with an increase in the dose. The TTX accumulation ratio (ratio (%) of accumulated TTX in each tissue (μg/tissue) to the administered dose (μg/individual)) of the skin (11.1-38.6) significantly decreased with an increase in the dose, whereas that of the liver (18.4-21.3) was almost constant irrespective of the dose. Immunohistochemical observations of the skin sections revealed TTX-positive signals in basal cells in LD, but as the dose increased, TTX-positive signals were also observed in the epidermis. In the liver sections, TTX-positive signals were rarely observed in LD and MD, but the TTX was distributed throughout the liver tissue in HD.


Preventive effect of Xanthoria parietina polyphenols on the complications of diabetes in white rat.
Polyphenols have shown antioxidant activity and an ability to prevent the toxic effects of oxidative stress in diabetes. The objective of this study was to evaluate the hypoglycemic and antioxidant effect of the methanolic extract of Xanthoria parietina on rats diabetes induced by streptozotocin (40 mg/g). The results obtained show that streptozotocin induces diabetes in the animal characterized by hyperglycemia, elevation of oxidative stress markers and a decrease of enzymatic and non-enzymatic antioxidant defense system. However, the methanolic extract results in a marked improvement in the antioxidant state in the liver. Indeed our results show a decrease in the malonyldialdehyde concentration of 25.91% and an increase in the reduced glutathione rate of 23.62%, an increase in the superoxide dismutase activity of 23.53% and catalase activity of 49.10%. The effect of the polyphenolic extract on the blood glucose level is tested on rats rendered hyperglycemic. The feeding with the extract showed a significant hypoglycaemic effect during 120 minutes of treatment. In conclusion, the present study suggests that Xanthoria parietina has a beneficial effect on the control of blood glucose, lipid profile and oxidative status, activating antioxidant enzymes and decreasing lipid peroxidation in the liver. Such treatments may help reduce the development of complications associated with diabetes.


Temperature-dependent electrical resistivity of macroscopic graphene nanoplatelet strips.
This paper studies the temperature dependence of the electrical resistivity of low-cost commercial graphene-based strips, made from a mixture of epoxy and graphene nanoplatelets. An equivalent homogenous resistivity model is derived from the joint use of experimental data and simulation results obtained by means of a full three-dimensional (3D) numerical electrothermal model. Three different types of macroscopic strips (with surface dimensions of cm2) are analyzed, differing in their percentage of graphene nanoplatelets. The experimental results show a linear trend of resistivity in a wide temperature range (-60°C to +60°C), and a negative temperature coefficient . The derived analytical model of temperature-dependent resistivity follows the simple law commonly adopted for conventional conducting materials, such us copper. The model is then validated by using the graphene strips as heating elements by exploiting the Joule effect. These results suggest that such materials can be used as thermistors in sensing or heating applications.


Successful unilateral thoracoscopy for bilateral ectopic mediastinal parathyroidectomy.
Ectopic parathyroid glands are frequently located in the thymus and may become hyperplasic in patients with secondary hyperparathyroidism. When medical management fails, surgical removal is required, using either a traditional open sternotomy approach or video-assisted thoracic surgery (VATS). We were able to excise large, bilateral, mediastinal parathyroid glands using only left VATS. To the authors' knowledge, this is the first reported case of the use of unilateral thoracoscopic subtotal thymectomy for the excision of bilateral ectopic mediastinal parathyroid glands.


Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG.
Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.


Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis.
The NF-kappaB signaling pathway promotes the immune response in rheumatoid arthritis (RA) and in rodent models of RA. NF-kappaB activity is regulated by the IKK-2 kinase during inflammatory responses. To elucidate how IKK-2 inhibition suppresses disease development, we used a combination of in vivo imaging, transcription profiling, and histopathology technologies to study mice with antibody-induced arthritis. ML120B, a potent, small molecule inhibitor of IKK-2, was administered to arthritic animals, and disease activity was monitored. NF-kappaB activity in diseased joints was quantified by in vivo imaging. Quantitative reverse transcriptase-polymerase chain reaction was used to evaluate gene expression in joints. Protease-activated near-infrared fluorescence (NIRF) in vivo imaging was applied to assess the amounts of active proteases in the joints. Oral administration of ML120B suppressed both clinical and histopathologic manifestations of disease. In vivo imaging demonstrated that NF-kappaB activity in inflamed arthritic paws was inhibited by ML120B, resulting in significant suppression of multiple genes in the NF-kappaB pathway, i.e., KC, epithelial neutrophil-activating peptide 78, JE, intercellular adhesion molecule 1, CD3, CD68, tumor necrosis factor alpha, interleukin-1beta, interleukin-6, inducible nitric oxide synthase, cyclooxygenase 2, matrix metalloproteinase 3, cathepsin B, and cathepsin K. NIRF in vivo imaging demonstrated that ML120B treatment dramatically reduced the amount of active proteases in the joints. Our data demonstrate that IKK-2 inhibition in the murine model of antibody-induced arthritis suppresses both inflammation and joint destruction. In addition, this study highlights how gene expression profiling can facilitate the identification of surrogate biomarkers of disease activity and treatment response in an experimental model of arthritis.


Premonitory epidermolysis bullosa acquisita mimicking eyelid dermatitis: successful treatment with rituximab and protein A immunoapheresis.
We report a unique case of a 71-year-old female patient with epidermolysis bullosa acquisita. The patient initially presented with the clinical symptoms of bilateral eyelid dermatitis that occurred several months prior to the development of oral and pharyngeal erosions and blisters. While no contact allergy was found by patch testing, direct immunofluorescence microscopy demonstrated linear deposits of IgG at the basement membrane zone. By indirect immunofluorescence microscopy on human salt-split skin, IgG antibodies bound to the dermal side of the split. Immunoblot analysis showed predominant IgG4 reactivity of the patient's serum with the recombinant non-collagenous-1 domain of type VII collagen. Because of treatment resistance to systemic corticosteroids, dapsone, and colchicine, we initiated a combination treatment of protein A immunoapheresis and rituximab. With this treatment, complete remission was achieved within 4 months. Our case highlights that epidermolysis bullosa acquisita may initially mimic an eyelid dermatitis. Consequently, dermatologists should be aware of this rare differential diagnosis of eyelid dermatitis where a contact allergy or atopic dermatitis is absent.


Thermotrophic effect of melatonin in adrenalectomized and thyroidectomized rats.
A single injection of 25 micrograms melatonin induced hyperthermia in rats. The mechanism(s) by which melatonin induces hyperthermia is not clear. In this study the thermotrophic effects of melatonin were studied in adrenalectomized (ADX) and thyroidectomized (TX) rats to ascertain if melatonin-induced hyperthermia is mediated through these glands, as both these glands play a significant role in mammalian thermoregulation. Melatonin (25 micrograms) was administered as a single subcutaneous injection at 06.00, 12.00, 18.00, and 24.00 h. Body temperatures were recorded, using an anal thermometer at hourly intervals, round the clock. In the scotophase the animals were located using dim red light and injected. Although the administration of melatonin to both intact and ADX rats resulted in a rise in body temperature, the effect was more pronounced in the former compared to the latter group. Melatonin induced hyperthermia only during the photophase of the diurnal cycle; in the scotophase the response was either poor or nil. In TX rats melatonin was ineffective in inducing hyperthermia in either the photophase or scotophase. The body temperatures of TX rats and melatonin-injected TX rats were parallel. The results indicate that in ADX rats melatonin induced minor hyperthermia, whereas in TX animals it failed to produce any hyperthermia. The findings suggest that melatonin induces hyperthermia probably through its action on thyroid activity. Other mechanisms of action cannot be ruled out, however.