Subacute neurological sequelae in mild COVID-19 outpatients.
Neurological aspect of COVID-19 is less understood compared to its respiratory and systemic effects. We aimed to define subacute neurological sequelae in patients who recovered from mild COVID-19. This study enrolled long COVID patients who had mild infection, were non-hospitalized, and admitted to our hospital with neurological complaints occurring after COVID-19. The evaluation included detailed history of the symptoms, neurological examination, blood tests and necessary investigations relevant to their personal medical situation, and also a retrospective inquiry about their respiratory and neurological status during the acute phase of infection. Descriptive statistical measures, Chi-square and Student's t-test were utilized. We identified 50 patients (29F/21M) with a mean age of 36.9 ± 1.6 (mean ± SEM). The average time from COVID-19 to admission was 99 days(min-max= 15-247). Most frequent neurological complaints were headache (42%) and cognitive dysfunction (42%). Sleep disturbance (36%), prolonged anosmia (30%), prolonged ageusia (22%), fatigue (22%), and dizziness (8%) followed. Most patients with headache experienced headache also as an acute manifestation of COVID-19 (p= 0.02). Acute-stage sleep disorders were found to be more associated with subacute cognitive symptoms than other central symptoms (p= 0.008). The most common neurological symptom in the acute phase was headache (74%). Six patients, despite the absence of any acute-stage neurological symptoms, presented with emergence of subacute neurological sequela. There were only five patients with pulmonary involvement during the acute stage, who were not different from the rest of the cohort in terms of neurological sequelae. There was no increase of inflammatory markers in the blood tests at the subacute stage, or no association of the symptoms to biochemical parameters. This study gives a description of neurological sequelae of mild COVID-19 at the subacute stage, in a relatively young group, and reveals that cognitive disturbances, as well as headache, are quite frequent.


[Epidemiological evaluation of the effectiveness of the obligatory isolation of whooping cough patients in schools].
Analysis of observations carried out under practical conditions (165 patients with pertussis from 48 foci) and the results of controlled epidemiological trial on the discontinuance of compulsory isolation of pertussis patients at schools (12 classes, 402 children) showed that isolation of the patients failed to stop the spread of infection in the focus. This was attributed to incomplete detection of the patients and their late isolation in conditions of wide incidence of mild forms and formes frustes of pertussis. When patients suffering from pertussis were left at school, there occurred no increase in the spread of the infection in the focus, in duration or severity of the disease and no increase of the period of discharge of the causative agent. However, the number of days of the patient's absence from school was greatly reduced. Taking into consideration the absence of an attack-like cough in patients with formes frustes, short duration and preponderance of the attacks at night in patients with a mild form of pertussis, no disturbances in the general condition of the child, and also no indications to the treatment, schoolchildren should be isolated by clinical indications only (pyrexia, marked catarrhal phenomena, frequent attack-like cough, complications, concomitant diseases); they can be admitted to school as soon as the mentioned signs subsided irrespective of the time lapse from the onset of the disease.


Effects of stressor predictability on escape learning and sleep in mice.
Controllable stress, modeled by escapable shock (ES), can produce significant alterations in post-stress sleep, including increased rapid eye movement (REM) sleep. Recent work has demonstrated that post-stress sleep may be influenced by stressor predictability, modeled by predictive auditory cues. In this study, we trained mice with ES, either signaled (SES) or unsignaled (UES) by auditory cues, and investigated the effects of predictability on escape learning and sleep associated with ES. Adult male BALB/cJ mice were implanted for recording electroencephalography and activity via telemetry. After the mice recovered from surgery, baseline sleep recordings were obtained. The mice were then randomly assigned to SES and UES conditions. Both groups had control over the duration of footshocks (0.5 mA; 5.0 sec maximum duration) by moving to the non-occupied chamber in a shuttlebox. SES mice were presented tones (90 dB, 2 kHz, 10 sec maximum duration) that started 5.0 sec prior to and co-terminated with footshocks. UES mice were presented identical tones that were not synchronized to shock presentation. ES training continued for 2 consecutive days (EST1 and EST2) with 20 footshock presentations (1 min inter-stimulus intervals). Seven days after EST2, the animals were re-exposed to the training chamber (context) alone for 30 min. Escape latency was used to determine successful or unsuccessful escape learning. Sleep was scored for 20 h for baseline and on each treatment day. Freezing in the training context was scored as a behavioral index of fear. Nine of 14 SES mice successfully learned escape (SESl), and 5 failed to learn escape (SESf). Compared with baseline, SESl mice, but not SESf mice, showed significantly increased post-shock REM. All UES mice learned escape and showed enhanced post-shock REM. Freezing and sleep did not differ among groups on the context re-exposure day. The results indicate that information available in a stressful situation can affect an animal's ability to learn an appropriate response and post-stress sleep. Machida M; Yang L; Wellman LL; Sanford LD. Effects of stressor predictability on escape learning and sleep in mice. SLEEP 2013;36(3):421-430.


So FCR, so good.
In this issue of Blood, Rossi et al show that certain predictive biomarkers are able to identify a subgroup of patients with chronic lymphocytic leukemia (CLL) who have an exceptionally good outcome following front-line therapy with the combination of fludarabine, cyclophosphamide, and rituximab (FCR).


Structural relaxation in supercooled orthoterphenyl.
We report molecular-dynamics simulation results performed for a model of molecular liquid orthoterphenyl in supercooled states, which we then compare with both experimental data and mode-coupling-theory (MCT) predictions, aiming at a better understanding of structural relaxation in orthoterphenyl. We pay special attention to the wave number dependence of the collective dynamics. It is shown that the simulation results for the model share many features with experimental data for real system, and that MCT captures the simulation results at the semiquantitative level except for intermediate wave numbers connected to the overall size of the molecule. Theoretical results at the intermediate wave number region are found to be improved by taking into account the spatial correlation of the molecule's geometrical center. This supports the idea that unusual dynamical properties at the intermediate wave numbers, reported previously in simulation studies for the model and discernible in coherent neutron-scattering experimental data, are basically due to the coupling of the rotational motion to the geometrical-center dynamics. However, there still remain qualitative as well as quantitative discrepancies between theoretical prediction and corresponding simulation results at the intermediate wave numbers, which call for further theoretical investigation.


Crystal structure of human bisphosphoglycerate mutase.
Bisphosphoglycerate mutase is a trifunctional enzyme of which the main function is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. The gene coding for bisphosphoglycerate mutase from the human cDNA library was cloned and expressed in Escherichia coli. The protein crystals were obtained and diffract to 2.5 A and produced the first crystal structure of bisphosphoglycerate mutase. The model was refined to a crystallographic R-factor of 0.200 and R(free) of 0.266 with excellent stereochemistry. The enzyme remains a dimer in the crystal. The overall structure of the enzyme resembles that of the cofactor-dependent phosphoglycerate mutase except the regions of 13-21, 98-117, 127-151, and the C-terminal tail. The conformational changes in the backbone and the side chains of some residues reveal the structural basis for the different activities between phosphoglycerate mutase and bisphosphoglycerate mutase. The bisphosphoglycerate mutase-specific residue Gly-14 may cause the most important conformational changes, which makes the side chain of Glu-13 orient toward the active site. The positions of Glu-13 and Phe-22 prevent 2,3-bisphosphoglycerate from binding in the way proposed previously. In addition, the side chain of Glu-13 would affect the Glu-89 protonation ability responsible for the low mutase activity. Other structural variations, which could be connected with functional differences, are also discussed.


Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of Leucopaxillus gentianeus.
A reinvestigation of the fruiting bodies of the mushroom Leucopaxillus gentianeus, allowed the isolation of two minor cucurbitane triterpenes, namely, cucurbitacin D (5) and the new metabolite 16-deoxycucurbitacin B (6). The latter compound lacks an oxygenated substituent at C-16, an unprecedented structural feature among congeners of cucurbitacin B. The cucurbitanes present in the fruiting bodies were compared with those extracted from mycelia grown on the modified Melin-Norkans (MMN) culture medium. Cucurbitacins B (1) and D (5), as well as leucopaxillones A (3) and B (4), were isolated from both sources; in contrast, 16-deoxycucurbitacin B (6) and a mixture of fatty acid esters of cucurbitacin B (2) were absent in the mycelia. A new triterpene, 18-deoxyleucopaxillone A (7), was isolated from the mycelia, but was not detected in the fruiting bodies. The antiproliferative activity of the isolated triterpenes was determined against the NCI-H460 human tumor cell line, in comparison with the antitumor compound topotecan, a well-known topoisomerase I inhibitor.


Transperineal retropubic approach in total pelvic exenteration for advanced and recurrent colorectal and anal cancer involving the penile base: technique and outcomes.
Complete pathological resection of locally advanced and recurrent anorectal cancer is considered the most important determinant of survival outcome. Involvement of the retropubic space with cancer threatening or involving the penile base poses specific challenges due to the potential for margin involvement and blood loss from the dorsal venous plexus. In the present study we evaluate a new transperineal surgical approach to excision of anterior compartment organs involved or threatened by cancer which facilitates exposure and visualisation of the bulbar urethra and the deep vein of the penis caudal to the retropubic space and penile base. A retrospective study was performed on male patients with tumour extension into the penile base treated at our institution using the transperineal surgical approach. Descriptive data for patient demographics, radiology, operative details, postoperative histology, complications and outcomes were collated. Ten male patients with tumour extension into the penile base were identified. Two patients had recurrent anal cancer, 6 had locally advanced primary rectal cancer and 2 had recurrent rectal cancer. All patients had exenterative surgery with excision of the penile base utilising the transperineal approach. All patients had R0 resection. No local recurrence developed after a median follow up period of 15 months. The transperineal approach to the penile base and retropubic space allows for high rates of R0 resection margin status with direct visualisation of the dorsal venous plexus, thereby minimising blood loss. In our experience, this technique is the preferred approach to excision of cancers threatening and involving the penile base and also for most male patients requiring total pelvic exenteration.


Discovery of the sinus node by Keith and Flack: on the centennial of their 1907 publication.
In 1839, Jan Evangelista Purkinje discovered a net of gelatinous fibres in the subendocardium of the heart. Walter Gaskell in the 1880s observed that the impulse of the heart began in the sinus venosus, and that this region had the most rhythmic ability. A conducting bundle between the atrium and the ventricle was found by Wilhelm His, Jr in 1893. In 1906, Sunao Tawara found a "complex knoten" of tissue at the proximal end of the His bundle. He concluded that this was the inception of an electrical conducting system which continued from the AV node through the bundle of His, divided into the bundle branches, and terminated as the Purkinje fibres. The collaboration of Arthur Keith and Martin Flack led to discovery of the sinus node, finalising the discovery of the electrical system of the heart and providing an anatomical answer to the baffling mystery: "Why does the heart beat?"


Reliability Concerns in Measuring Respondent Skin Tone by Interviewer Observation.
The current study assesses the intercoder reliability of one of the most important skin tone measurement instruments-the Massey-Martin scale. This scale is used in several high-profile social surveys, but has not yet been psychometrically evaluated. The current evaluation is only possible because, for the first time, the General Social Survey's 2010-2014 panel used the instrument to guide interviewers' skin tone observation of the same respondents in two different years (2012 and 2014). Despite the widespread use of the Massey-Martin scale to investigate potential effects of skin tone on social attitudes and outcomes, the data suggest that the measure has low intercoder reliability. Implications for researchers and survey practitioners are discussed.


Plasticity and learning in a network of coupled phase oscillators.
A generalized Kuramoto model of coupled phase oscillators with a slow varying coupling matrix is studied. The dynamics of the coupling coefficients is driven by the phase difference of pairs of oscillators in such a way that the coupling strengthens for synchronized oscillators and weakens for nonsynchronized pairs. The system possesses a family of stable solutions corresponding to synchronized clusters of different sizes. A particular cluster can be formed by applying external driving at a given frequency to a group of oscillators. Once established, the synchronized state is robust against noise and small variations in natural frequencies. The phase differences between oscillators within the synchronized cluster can be used for information storage and retrieval.


Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc.
Human telomerase reverse transcriptase (hTERT) underlies cancer cell immortalization, and the expression of hTERT is regulated strictly at the gene transcription. Here, we report that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation. Silencing Ets2 induces a decrease of hTERT gene expression and increase in human breast cancer cell death. Reconstitution with recombinant hTERT rescues the apoptosis induced by Ets2 depression. In vitro and in vivo analyses show that Ets2 binds to the EtsA and EtsB DNA motifs on the hTERT gene promoter. Mutation of either Ets2 binding site reduces the hTERT promoter transcriptional activity. Moreover, Ets2 forms a complex with c-Myc as demonstrated by co-immunoprecipitation and glutathione S-transferase pulldown assays. Immunological depletion of Ets2, or mutation of the EtsA DNA motif, disables c-Myc binding to the E-box, whereas removal of c-Myc or mutation of the E-box also compromises Ets2 binding to EtsA. Thus, hTERT gene expression is maintained by a mechanism involving Ets2 interactions with the c-Myc transcription factor and the hTERT gene promoter, a protein-DNA complex critical for hTERT gene expression and breast cancer cell proliferation.


A step in the right direction: an open-design pedometer algorithm for dogs.
Accelerometer-based technologies could be useful in providing objective measures of canine ambulation, but most are either not tailored to the idiosyncrasies of canine gait, or, use un-validated or closed source approaches. The aim of this paper was to validate algorithms which could be applied to accelerometer data for i) counting the number of steps and ii) distance travelled by a dog. To count steps, an approach based on partitioning acceleration was used. This was applied to accelerometer data from 13 dogs which were walked a set distance and filmed. Each footfall captured on video was annotated. In a second experiment, an approach based on signal features was used to estimate distance travelled. This was applied to accelerometer data from 10 dogs with osteoarthritis during normal walks with their owners where GPS (Global Positioning System) was also captured. Pearson's correlations and Bland Altman statistics were used to compare i) the number of steps measured on video footage and predicted by the algorithm and ii) the distance travelled estimated by GPS and predicted by the algorithm. Both step count and distance travelled could be estimated accurately by the algorithms presented in this paper: 4695 steps were annotated from the video and the pedometer was able to detect 91%. GPS logged a total of 20,184 m meters across all dogs; the mean difference between the predicted and GPS estimated walk length was 211 m and the mean similarity was 79%. The algorithms described show promise in detecting number of steps and distance travelled from an accelerometer. The approach for detecting steps might be advantageous to methods which estimate gross activity because these include energy output from stationary activities. The approach for estimating distance might be suited to replacing GPS in indoor environments or others with limited satellite signal. The algorithms also allow for temporal and spatial components of ambulation to be calculated. Temporal and spatial aspects of dog ambulation are clinical indicators which could be used for diagnosis or monitoring of certain diseases, or used to provide information in support of canine weight-loss programmes.


Systematic search for wide periodic windows and bounds for the set of regular parameters for the quadratic map.
An efficient method to find positions of periodic windows for the quadratic map f(x)=ax(1-x) and a heuristic algorithm to locate the majority of wide periodic windows are proposed. Accurate rigorous bounds of positions of all periodic windows with periods below 37 and the majority of wide periodic windows with longer periods are found. Based on these results, we prove that the measure of the set of regular parameters in the interval [3,4] is above 0.613960137. The properties of periodic windows are studied numerically. The results of the analysis are used to estimate that the true value of the measure of the set of regular parameters is close to 0.6139603.


A fusogenic dengue virus-derived peptide enhances antitumor efficacy of an antibody-ribonuclease fusion protein targeting the EGF receptor.
Due to its frequent overexpression in a variety of solid tumors the epidermal growth factor receptor (EGFR) is a well-established target for therapeutic interventions in epithelial cancers. In order to target EGFR in head and neck cancer, we have generated a ribonuclease (RNase) fusion protein comprising a humanized anti-EGFR antibody single-chain Fv fragment (scFv) and Ranpirnase, an RNase from Rana pipiens. Fusion of Ranpirnase to the N-terminus of the scFv via a flexible glycine-serine linker (G4S)3 resulted in very poor cytotoxicity of the fusion protein. As endosomal accumulation and lysosomal degradation have been reported to diminish the antitumor efficacy of ribonuclease or toxin-based immunoagents, we explored a fusion peptide from dengue virus that has been reported to be involved in the endosomal escape of the virus. This peptide was introduced as a linker between Ranpirnase and the scFv moiety. The modified immunoRNase exhibited exceptionally high cytotoxicity toward EGFR-expressing head and neck cell lines without affecting specificity. These results indicate that endosomal entrapment needs to be considered for Ranpirnase-based immunoagents and might be overcome by the use of tailored transduction domains from viral proteins.


Healing potential of curcumin nanomicelles in cutaneous burn wounds: an in vitro and in vivo study.
Curcumin is the active substance of turmeric and has been shown to enhance the healing potential of burn wounds. However, its high hydrophobicity and rapid degradability are great challenges for its clinical applications. The development of new curcumin formulations may provide a potential solution to these issues. In this study, we investigated the use of curcumin nanomicelles for wound dressing and evaluated their effects on fibroblast migration and proliferation in vitro. We found that the application of curcumin nanomicelles to the wounds significantly improved wound contraction and increased the expression of transforming growth factor-1 and basic fibroblast growth factor at day 14 of the healing process. Furthermore, curcumin nanomicelles reduced the expression of interleukin-1 at days 7 and 14 post-wounding. Histopathological analysis revealed that the curcumin nanomicelles-treated burn wounds exhibited more organized granulation tissue, improved angiogenesis, and enhanced re-epithelialization. Additionally, the curcumin treatment led to increased hydroxyproline content and enhanced TGF-β1 expression level in the wounds. The in vitro studies also demonstrated that the curcumin nanomicelles induced proliferation and migration of fibroblasts. Overall, our findings suggest that curcumin nanomicelles can be a promising candidate for the treatment of burn wounds.


The burden of ischemic heart disease attributable to ambient and household particulate matter pollution, 1990-2019: a global analysis.
Elevated risk of ischemic heart disease (IHD) is associated with exposure to fine particulate matter. However, there is limited data on trends and comparisons in the global burden of IHD due to household air pollution from solid fuels (HAP) and ambient particulate matter pollution (APMP), particularly in regions of varying socio-economic levels. Based on the Global Burden of Disease Study 2019 (GBD 2019), we obtained age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (ASDR) of IHD due to APMP and HAP from 1990 to 2019. Trends in the burden of IHD attributable to APMP and HAP during the period 1990 to 2019 were calculated by Joinpoint models. We estimated the relationship between ASMR with the socio-demographic indexes (SDI) and the health care accessibility and quality (HAQ) index by the Loess regression model. In 2019, the global burden of IHD ASMR attributed to APMP stabilized, but the most significant increases were observed in low-middle SDI regions. The global IHD ASMR attributed to APMP was 16.60 [95% Uncertainty Interval (UI), 13.61 to 19.44] per 100,000 population, with the highest APMP burden in middle SDI regions. From 1990 to 2019, the global ASMR for HAP-attributable IHD declined. The global ASMR of IHD attributable to HAP in 2019 was 6.30 (95% UI, 4.28 to 8.80) per 100,000 population, with the highest burden observed in the low SDI regions. From 1990 to 2019, the global burden of ASMR and ASDR of IHD attributable to APMP showed stabilization, whereas the HAP burden exhibited a decrease. There are a large burden of APMP particularly in middle SDI countries and a higher burden of HAP in low SDI countries. The burden of IHD due to APMP and HAP in men, the elderly, and populations in low, medium, and low SDI regions should be noticed.


Firing rates and dynamic correlated activities of ganglion cells both contribute to retinal information processing.
In the present study, the electrical activities of paired retinal ganglion cells, under full field light stimuli with a variety of chromatic configurations, were recorded from a small functioning piece of retina using multi-electrode array (MEA). Neurons that had increased firings at light-ON and -OFF transients and did not show color-opponent properties were investigated. Single neuronal analysis showed that firing rate of each individual neuron was dependent on the intensity of illumination. Multi-unit analyses revealed that adjacent neurons often fired in synchrony in response to light stimulation. However, in some cases, the strength of correlation between the paired neurons was higher when the retina was exposed to red or green light, and the correlation was attenuated when yellow or white light was given. This seems to suggest that the ensemble activity of non-color-opponent ganglion cells might partly participate in color-information processing, with the red- and green-pathway inputs influencing each other. Such arrangement reflects principle of parsimony: the firing rates of single neuron represent the luminance intensity, and the correlated activities may tell the brain about the color information.


Transient transmembrane secretion of H2O2: a mechanism for the citral-caused inhibition of aflatoxin production from Aspergillus flavus.
A polydopamine-Fe3O4 nanocomposite-based H2O2 electrochemical sensor is fabricated to real-time monitor the transmembrane release of reactive oxygen species from citral-treated Aspergillus flavus, revealing a mechanism involving transient transmembrane secretion of H2O2 for the citral-caused inhibition of aflatoxin production from a fungus for the first time.


Changes of neutrophil elastase and alpha 1-antitrypsin in systemic lupus erythematosus.
Contents of HNE and alpha 1-AT and the positive rates of PMN-Ab in patients with SLE were measured and tested by ELISA, immunodiffusion and protein-A rosette, respectively, and it was found that plasma HNE content was significantly higher in patients with SLE (61.0 +/- 13.9 ng/ml) than in normal controls (33.7 +/- 6.7 ng/ml, P less than 0.001), while plasma alpha 1-AT in patients with SLE (2.79 +/- 0.47 mg/ml) was similar to that in normal controls (2.55 +/- 0.38 mg/ml, P greater than 0.6). The positive rate of PMN-Ab in SLE (9.8 +/- 6.5) was also significantly higher than that in normal (0.17 +/- 0.2%, P less than 0.001). The results suggest that there is an imbalance between plasma HNE and alpha 1-AT in SLE regardless of WBC or the positive rate of PMN-Ab, with this imbalance probably being due to activation of neutrophils following multiorgan damage of SLE.


Immunobiology of Acute Chorioamnionitis.
Acute chorioamnionitis is characterized by neutrophilic infiltration and inflammation at the maternal fetal interface. It is a relatively common complication of pregnancy and can have devastating consequences including preterm labor, maternal infections, fetal infection/inflammation, fetal lung, brain, and gastrointestinal tract injury. In this review, we will discuss current understanding of the pathogenesis, immunobiology, and mechanisms of this condition. Most commonly, acute chorioamnionitis is a result of ascending infection with relatively low-virulence organisms such as the Ureaplasma species. Furthermore, recent vaginal microbiome studies suggest that there is a link between vaginal dysbiosis, vaginal inflammation, and ascending infection. Although less common, microorganisms invading the maternal-fetal interface via hematogenous route (e.g., Zika virus, Cytomegalovirus, and Listeria) can cause placental villitis and severe fetal inflammation and injury. We will provide an overview of the knowledge gleaned from different animal models of acute chorioamnionitis and the role of different immune cells in different maternal-fetal compartments. Lastly, we will discuss how infectious agents can break the maternal tolerance of fetal allograft during pregnancy and highlight the novel future therapeutic approaches.


Accelerated aging studies of UHMWPE. I. Effect of resin, processing, and radiation environment on resistance to mechanical degradation.
The resin and processing route have been identified as potential variables influencing the mechanical behavior, and hence the clinical performance, of ultra-high molecular weight polyethylene (UHMWPE) orthopedic components. Researchers have reported that components fabricated from 1900 resin may oxidize to a lesser extent than components fabricated from GUR resin during shelf aging after gamma sterilization in air. Conflicting reports on the oxidation resistance for 1900 raise the question of whether resin or manufacturing method, or an interaction between resin and manufacturing method, influences the mechanical behavior of UHMWPE. We conducted a series of accelerated aging studies (no aging, aging in oxygen or in nitrogen) to systematically examine the influence of resin (GUR or 1900), manufacturing method (bulk compression molding or extrusion), and sterilization method (none, in air, or in nitrogen) on the mechanical behavior of UHMWPE. The small punch testing technique was used to evaluate the mechanical behavior of the materials, and Fourier transform infrared spectroscopy was used to characterize the oxidation in selected samples. Our study showed that the sterilization environment, aging condition, and specimen location (surface or subsurface) significantly affected the mechanical behavior of UHMWPE. Each of the three polyethylenes evaluated seem to degrade according to a similar pathway after artificial aging in oxygen and gamma irradiation in air. The initial ability of the materials to exhibit post-yield strain hardening was significantly compromised by degradation. In general, there were only minor differences in the aging behavior of molded and extruded GUR 1050, whereas the molded 1900 material seemed to degrade slightly faster than either of the 1050 materials.


Evaluation of the Use of Zero-Augmented Regression Techniques to Model Incidence of Campylobacter Infections in FoodNet.
The Foodborne Diseases Active Surveillance Network (FoodNet) is currently using a negative binomial (NB) regression model to estimate temporal changes in the incidence of Campylobacter infection. FoodNet active surveillance in 483 counties collected data on 40,212 Campylobacter cases between years 2004 and 2011. We explored models that disaggregated these data to allow us to account for demographic, geographic, and seasonal factors when examining changes in incidence of Campylobacter infection. We hypothesized that modeling structural zeros and including demographic variables would increase the fit of FoodNet's Campylobacter incidence regression models. Five different models were compared: NB without demographic covariates, NB with demographic covariates, hurdle NB with covariates in the count component only, hurdle NB with covariates in both zero and count components, and zero-inflated NB with covariates in the count component only. Of the models evaluated, the nonzero-augmented NB model with demographic variables provided the best fit. Results suggest that even though zero inflation was not present at this level, individualizing the level of aggregation and using different model structures and predictors per site might be required to correctly distinguish between structural and observational zeros and account for risk factors that vary geographically.


A systematic analysis of nucleosome core particle and nucleosome-nucleosome stacking structure.
Chromatin condensation is driven by the energetically favourable interaction between nucleosome core particles (NCPs). The close NCP-NCP contact, stacking, is a primary structural element of all condensed states of chromatin in vitro and in vivo. However, the molecular structure of stacked nucleosomes as well as the nature of the interactions involved in its formation have not yet been systematically studied. Here we undertake an investigation of both the structural and physico-chemical features of NCP structure and the NCP-NCP stacking. We introduce an "NCP-centred" set of parameters (NCP-NCP distance, shift, rise, tilt, and others) that allows numerical characterisation of the mutual positions of the NCPs in the stacking and in any other structures formed by the NCP. NCP stacking in more than 140 published NCP crystal structures were analysed. In addition, coarse grained (CG) MD simulations modelling NCP condensation was carried out. The CG model takes into account details of the nucleosome structure and adequately describes the long range electrostatic forces as well as excluded volume effects acting in chromatin. The CG simulations showed good agreement with experimental data and revealed the importance of the H2A and H4 N-terminal tail bridging and screening as well as tail-tail correlations in the stacked nucleosomes.


Is endoscopic therapy the treatment of choice in all patients with chronic pancreatitis?
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas characterized by destruction of the pancreatic parenchyma with subsequent fibrosis that leads to pancreatic exocrine and endocrine insufficiency. Abdominal pain and local complications (bile duct or duodenal stenosis and pancreatic tumor) secondary to CP are indications for therapy. At the beginning, medical therapy is used. More invasive treatment is recommended for patients with pancreatic duct stones (PDS) and pancreatic obstruction in whom standard medical therapy is not sufficient. Recently, Clarke et al assessed the long-term effectiveness of endoscopic therapy (ET) in CP patients. The authors compared ET with medical treatment. They reported that ET was clinically successful in 50% of patients with symptomatic CP. In this commentary, current CP treatment, including indications for ET and surgery in CP patients, is discussed. Recommendations for endoscopic treatment of CP according to the European Society of Gastrointestinal Endoscopy Clinical Guidelines are reviewed. Different surgical methods used in the treatment of CP patients are also discussed. ET is the most useful in patients with large PDS, pancreatic duct obstruction and dilation. It should be the first-line option because it is less invasive than surgery. Surgery should be the first-line option in patients in whom ET has failed or in those with a pancreatic mass with suspicion of malignancy. ET is a very effective and less invasive procedure, but it cannot be recommended as the treatment of choice in all CP patients.


Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma.
Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients.


Pharmacokinetic and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Streptococcus pneumoniae.
Infections caused by Streptococcus pneumoniae place a considerable personal and economic burden on both patients and healthcare systems. As the resistance of S. pneumoniae to older antimicrobial agents such as penicillin, cephalosporins, and macrolides has increased, new antimicrobials with good activity against S. pneumoniae have been developed. The newer fluoroquinolones, including levofloxacin, gatifloxacin and moxifloxacin provide a safe and easy tool in the treatment of S. pneumoniae infections. However, there have been recent reports of levofloxacin-resistant strains of S. pneumoniae. Pharmacokinetics and pharmacodynamics can be used to determine which fluoroquinolone delivers the best coverage against S. pneumoniae, and also the 24-h AUC/MIC ratio (the AUIC) required to impede the emergence of bacterial resistance. Monte Carlo analysis suggests that moxifloxacin, with 4-8-fold greater activity and higher AUIC against S. pneumoniae than levofloxacin or gatifloxacin, provides the best coverage in terms of probability of cure and probability of minimizing emergence of resistance.


Update on programs for achieving Specialist in Blood Banking certification in the United States: 2023.
A person who has achieved the Specialist in Blood Banking (SBB) certification is a medical laboratory scientist who receives advanced training in blood banking and transfusion medicine and has passed an examination given by the American Society for Clinical Pathology. There are several pathways or "eligibility routes" to qualify for the examination to obtain SBB certification, with the most common route involving enrollment in a Commission on Accreditation of Allied Health Education Programs-accredited SBB program. The goal of this study was to compile information about the current accredited SBB programs in the United States and SBB exam statistics for purposes of assessing changes in the programs and detecting trends in SBB exam takers and pass rates. SBB program coordinators were surveyed about qualitative and quantitative aspects of their programs. Current data, changes over time, and nationally available data were tabulated for comparison. This information may be helpful for all medical laboratory scientists interested in considering further studies and certification in blood banking and transfusion medicine.


Clinical effect of abdominal aortic aneurysm endografting: 7-year concurrent comparison with open repair.
We compared the effectiveness and clinical outcome of open repair versus endovascular aortic aneurysm repair (EVAR) in achieving prevention of abdominal aortic aneurysm (AAA)-related death and graft-related complications. Over 7 years from 1997 to 2003, 1119 consecutive patients underwent elective treatment of infrarenal AAAs, 585 with open repair and 534 with EVAR. Patients were regularly followed up at 1, 6, 12 months, and every 6 months thereafter, in EVAR group, and at 3 and 12 months, and yearly thereafter after open repair. Preoperative, intraoperative, and follow-up data were stored in a prospective database. Median follow-up was similar in the 2 groups: 33 months (interquartile range [IQR], 13-50 months) in the EVAR group vs 35 months (IQR, 15-54 months) in the open repair group. EVAR group patients were older than patients in the open repair group: 73 years vs 72 years (P = .04). There were statistical significant differences between the EVAR group and the open repair group with respect to AAA median diameter (52 mm vs 56 mm), coronary disease rate (46% vs 37%; P = .001), pulmonary disease rate (56% vs 38%; P < .0001), and American Society of Anesthesiologists IV score rate (16% vs 6%; P < .0001). Thirty-day mortality in the EVAR group was 0.9% (5 of 534 patients), compared with 4.1% (24 of 585 patients; P = .001) in the open repair group, and major morbidity was 9.1% (49 of 534 patients) vs 18.6% (109 of 585 patients; P < .0001), respectively. The incidence of secondary procedures in the EVAR group was 15.7%, compared with 3% in the open repair group (P < .0001). There were no deaths related to secondary procedures in either group. Six AAAs (1.1%) ruptured after EVAR, 3 of which were fatal; in the open repair group 1 patient (0.2%) underwent successful repeat operatation to treat iliac pseudoaneurysm rupture 5 years after the original procedure. Kaplan-Meier estimates for freedom from aneurysm-related death at 84 months were 97.5% in the EVAR group and 95.9% in the open repair group (log rank test, P = .008). Kaplan-Meier survival estimates at 84 months were 67.1% in the open repair group and 66.9% in the EVAR group (P = NS). At the same interval the risk for secondary procedures was 49.4% for the EVAR group and 7.1% for the open repair group. Of the 11 variables analyzed with logistic analysis, open surgery (hazard ratio [HR], 11; 95% confidence interval [CI], 2.5-54.2; P = .002), American Society of Anesthesiologists IV score (HR, 7.1; 95% CI, 2.7-18.8; P = .0001), and age (HR, 1.06; 95% CI, 1.04-1.13; P = .04) were positive independent predictors of perioperative mortality. Our data suggest that at a maximum follow-up of 7 years, patients who undergo EVAR show lower perioperative and late aneurysm-related mortality compared with a younger and substantially healthier group of patients with aneurysms treated with open repair. The higher need for secondary procedures in the endovascular group did not affect superiority of the overall performance of EVAR in the early and late intervals.


Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade.
Objective. The purpose of the study was to elucidate the molecular mechanism of tenacissoside H (TDH) inhibiting esophageal carcinoma infiltration and proliferation. Methods. In vitro, EC9706 cells were treated with TDH. Cells proliferation and cell cycle were assayed. PI3K and NF-κB mRNAs expression were determined by real time PCR. In vivo, model of nude mice with tumor was established. Mice were treated with TDH. Inhibition ratio of tumor volume was calculated. PCNA expression was examined. Protein expression in PI3K/Akt-NF-κB signaling pathway was determined. Results. In vitro, TDH significantly inhibited cells proliferation in a time-and-dose-dependent manner. TDH arrested the cell cycle in S phase and significantly inhibited PI3K and NF-κB mRNA expression, compared with blank controlled group (P < 0.05). In vivo, TDH strongly inhibits tumor growth and volume. PCNA expression was significantly decreased after treatment of TDH. TDH downregulated proteins expression in PI3K/Akt-NF-κB transduction cascade (P < 0.05). Conclusion. TDH inhibited esophageal carcinoma infiltration and proliferation both in vitro and in vivo. The anticancer activity has relation to arresting the cell cycle at the S phase, inhibited the PCNA expression of transplanted tumors in nude mice, and regulated the protein expression in the PI3K/Akt-NF-κB transduction cascade.


Decolonization of Staphylococcus aureus in Healthcare: A Dermatology Perspective.
The bacterium Staphylococcus aureus is responsible for significant morbidity, mortality, and financial burden in healthcare. It easily colonizes susceptible patients and can cause recurrent infections, especially in populations at risk. In addition to treating sequelae of infections, there is a growing body of literature aimed at decolonizing susceptible patients in order to prevent infection and also to prevent spread. Such strategies are widely employed in surgical, intensive care, and hospitalist fields. Staphylococcus aureus involvement has been implicated in the pathogenesis and persistence of many dermatologic diseases that are treated in the outpatient setting. This review serves to summarize current evidence for the management of Staphylococcus aureus colonized patients, as well as the evidence available for decolonization. We further characterize the role that colonization may play in atopic dermatitis, recurrent infections, hand eczema, cutaneous T-cell lymphoma, and also in surgical infections after Mohs surgery.


Effects of tea constituents on cell cycle progression of human leukemia U937 cells.
Tea and tea constituents are known to induce apoptosis in a variety of cancerous cells, suggesting their beneficial effects as chemopreventive agents. Previous studies have shown that low molecular weight constituent catechins and high molecular weight fractions of tea have the apoptosis-inducing activity, but that their action mechanisms may be different. Since cell cycle arrest is known to be one of the underlying mechanisms of apoptosis, we examined the effects of these tea constituents on cell cycle progression of human leukemia U937 cells. The results showed that the high molecular weight fractions of green tea and black tea caused G2/M arrest associated with up-regulation of p21/Waf1, but that epigallocatechin gallate, a major component of green tea catechins, gave little effects of cell cycle progression and p21/Waf1 expression. Thus, the present results suggest the difference in the apoptosis-induction mechanism between the two types of tea constituents.


A safe treatment for congenital fibrovascular pupillary membrane.
The purpose of this study was to describe the clinical features and management of fibrovascular pupillary membrane. Four patients with congenital fibrovascular pupillary membrane were recruited. Comprehensively, ophthalmic examinations were performed. Peripheral iridectomy was performed to create a tunnel for blunt dissection of adhesion between the membrane and the lens capsule. Bipolar radiofrequency diathermy was then used to cut the membrane utilizing its coagulation effect. All four patients received uneventful membranectomy surgeries. The follow-up duration ranged from 9 to 16 months. All patients recovered well. Visual behavior was central and steady. The natural pupil size ranged from 2 to 3 mm. No sign of visual axis obstruction, cataract formation, or intraocular pressure elevation was detected during the follow-up. No second surgery was needed for all patients. Fibrovascular pupillary membrane is a rare unilateral disease impairing visual acuity in children. Using the technique combining peripheral iridectomy with bipolar radiofrequency, diathermy can simplify the traditional surgery procedures and reduce the risks when removing fibrovascular pupillary membranes.


Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced Transcriptome of Human Cells.
One of the major challenges in environmental science is monitoring and assessing the risk of complex environmental mixtures. In vitro bioassays with limited key toxicological end points have been shown to be suitable to evaluate mixtures of organic pollutants in wastewater and recycled water. Omics approaches such as transcriptomics can monitor biological effects at the genome scale. However, few studies have applied omics approach in the assessment of mixtures of organic micropollutants. Here, an omics approach was developed for profiling bioactivity of 10 water samples ranging from wastewater to drinking water in human cells by a reduced human transcriptome (RHT) approach and dose-response modeling. Transcriptional expression of 1200 selected genes were measured by an Ampliseq technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial dilutions of each sample. Concentration-effect models were used to identify differentially expressed genes (DEGs) and to calculate effect concentrations (ECs) of DEGs, which could be ranked to investigate low dose response. Furthermore, molecular pathways disrupted by different samples were evaluated by Gene Ontology (GO) enrichment analysis. The ability of RHT for representing bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the results of previous in vitro bioassays. Finally, the relative potencies of the mixtures indicated by RHT analysis were consistent with the chemical profiles of the samples. RHT analysis with human cells provides an efficient and cost-effective approach to benchmarking mixture of micropollutants and may offer novel insight into the assessment of mixture toxicity in water.


Color vision varies more among populations than among species of live-bearing fish from South America.
Sensory Bias models for the evolution of mate preference place a great emphasis on the role of sensory system variation in mate preferences. However, the extent to which sensory systems vary across- versus within-species remains largely unknown. Here we assessed whether color vision varies in natural locations where guppies (Poecilia reticulata) and their two closest relatives, Poecilia parae and Poecilia picta, occur in extreme sympatry and school together. All three species base mate preferences on male coloration but differ in the colors preferred. Measuring opsin gene expression, we found that within sympatric locations these species have similar color vision and that color vision differed more across populations of conspecifics. In addition, all three species differ across populations in the frequency of the same opsin coding polymorphism that influences visual tuning. Together, this shows sensory systems vary considerably across populations and supports the possibility that sensory system variation is involved in population divergence of mate preference.


Variations in bovine embryo production between individual donors for OPU-IVF are closely related to glutathione concentrations in oocytes during in vitro maturation.
Variations in embryo production between individual oocyte donors represent a serious problem in cattle production, when implementing ovum pick-up (OPU) and in vitro maturation (IVM) of oocytes. However, the precise cause of this problem is unknown. Here, we aimed to investigate the relationship between the glutathione (GSH) concentration in IVM oocytes and embryo development to explore a potential cause of the variations between individual donors. First, we found a high positive correlation (r = 0.80) between the GSH concentration in IVM oocytes and the blastocyst development rate of oocytes collected in the same OPU session for each donor (N = 11). Second, we selected two donors with significantly different blastocyst development rates. In samples from these donors, we examined the dynamics of oocytes GSH concentrations, and the gene expression of the glutathione synthetase (GSS) and glutathione peroxidase (GPX) genes in cumulus-oocyte complexes (COCs) during IVM. At 0 and 24 h after IVM, oocytes from the donor with the highest blastocyst development rate (high donor) exhibited significantly higher oocyte GSH concentrations than oocytes from the donor with the lowest blastocyst development rate (low donor, P < 0.05). At 4 and 9 h after IVM, GSH concentrations gradually decreased in oocytes from both donors. The GSS expression levels at 0, 4, and 9 h after IVM were significantly higher in COCs from the high donor than in COCs from the low donor (P < 0.05). The expression levels of GPX, a marker of oxidative stress, at 4 and 9 h after IVM were significantly higher in COCs from the low donor than in COCs from the high donor. Finally, adding cysteine into the IVM medium of oocytes collected in the same OPU session from the low donor significantly increased oocytes GSH concentrations and blastocyst development rates (P < 0.05). In conclusion, we showed that oocyte GSH concentrations were related to the differences in embryo development between individual donors. Our results suggested that increasing the GSH concentration in IVM oocytes could reduce the individual differences in embryo production between donors.


Pulse oximetry: what the nurse needs to know.
Rationale and key points Measurement of peripheral oxygen saturation (SpO2) is used to identify early hypoxia in patients and evaluate the effectiveness of oxygen therapy. Nurses should be aware of the procedure for using a pulse oximeter to measure SpO2 levels and the normal range for SpO2 readings. » A pulse oximeter is used to measure SpO2 levels, and involves placing a probe on the patient's finger, toe or ear lobe. » A SpO2 level of less than 90% is a clinical emergency. If the SpO2 level is below 94%, the nurse should assume the patient is hypoxic until proven otherwise, and therefore they may require supplemental oxygen administration. » Nurses should be aware of the factors that might affect SpO2 readings, including anaemia, peripheral vasoconstriction, dark skin tone and skin discolouration.


The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47.
The basic helix-loop-helix (bHLH) transcription factors E12 and E47 regulate cellular differentiation and proliferation in diverse cell types. While looking for proteins that bind to E12 and E47 by the yeast interaction trap, we isolated the rat (r) homologue of the human (h) polymyositis-scleroderma autoantigen (PM-Scl), which has been localized to the granular layer of the nucleolus and to distinct nucleocytoplasmic foci. The rPM-Scl and hPM-Scl homologues are 96% similar and 91% identical. We found that rPM-Scl mRNA expression was regulated by growth factor stimulation in cultured rat aortic smooth muscle cells. rPM-Scl bound to E12 and E47 but not to Id3, Gax, Myb, OCT-1, or Max. The C terminus of rPM-Scl (amino acids 283-353) interacted specifically with a 54-amino acid domain in E12 that is distinct from the bHLH domain. Finally, cotransfection of rPM-Scl and E47 specifically increased the promoter activity of a luciferase reporter construct containing an E box and did not affect the basal activity of the reporter construct. rPM-Scl appears to be a novel non-HLH-interacting partner of E12/E47 that regulates E2A protein transcription.


Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer.
MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.


Microwave to near-infrared conversion with a millimeter-scale wireless laser for activating molecular transducers.
Light-activated molecular transducers enable precise manipulation of biological processes and are thus powerful tools for studying or treating disease. Their use in vivo, however, is currently limited by the low penetration of light through biological tissue. While electromagnetic fields at microwave frequencies can penetrate thick tissue, they do not provide direct control over molecular transducers. Here, we describe a miniaturized, wirelessly powered laser capable of delivering high intensity near-infrared light in tissue. The device is about 2.5 mm in the largest dimension, weighs less than 30 mg, and can be wirelessly powered through >1 cm of tissue. This device could be used in emerging bioelectronics-based treatments that combine the precision of light with the penetration depth of microwaves.


Increased rate of factor V Leiden mutation in patients with cerebral venous thrombosis.
We investigated the association between cerebral venous thrombosis and hereditary resistance to activated protein C (APC) in 12 consecutive German patients with non-fatal cerebral venous thrombosis and in 187 controls without a history of thrombotic disorder. Three patients (25%) had a mutation in the factor V Leiden gene against only one subject in the control group. This difference was significant (P < 0.05), with an odds ratio of 11.7 (1.5-87; 95% confidence interval). Two patients carrying the mutation had additional common risk factors for thrombosis, and 2 had a positive family history of thromboembolism. We conclude that inherited APC resistance by a mutation in factor V Leiden is an important risk factor in non-fatal cerebral venous thrombosis. We recommend testing for APC resistance and, if abnormal for factor V Leiden mutation in patients with cerebral venous thrombosis.


KIT receptor-positive cells in the bovine corpus luteum are primarily theca-derived small luteal cells.
The tyrosine kinase KIT receptor, the protooncogene CD117, plays a key role in growth and maturation of oocytes and follicles. Relevant data are sparse for the corpus luteum (CL). We first confirmed the presence of KIT mRNA and KIT protein in bovine CL homogenates. We then localized KIT-positive (KIT+) cells in CL sections by immunohistochemistry. At the CL stage of early development, the former theca transforming into capsule/septa showed a strong band-like KIT+ immunoresponse. In addition, CD45+ leukocytes in septa included subpopulations of CD45+/KIT+ and CD14+/KIT+ leukocytes as validated by double immunofluorescence localization. At the early secretory stage, KIT+ cells appeared within the septa/capsule region and in the periphery of the CL parenchyma, there forming a complex network. This was separate from the capillary bed as determined by double staining for CD117 and FVIII-related endothelial cell antigen (FVIIIr). The KIT+ network coincided with cells positive for cytochrome P450 17alpha-hydroxylase, a thecal cell-specific enzyme. The late secretory stage was defined by an advanced manifestation of the KIT+ network in the CL periphery. At the stage of regression, the KIT+ network was absent. The CL of pregnancy expressed high levels of KIT mRNA and KIT protein uniformly throughout pregnancy. The KIT+ immunolocalization revealed small fibroblast-like cells, luteal cells with granules, and clusters of large luteal cells with staining of the cell membrane. We conclude that a majority of KIT+ cells in the bovine CL are primarily theca-derived small luteal cells, and that a minority represent KIT+ leukocytes, in some cases KIT+ monocytes.


The jellification of north temperate lakes.
Calcium (Ca) concentrations are decreasing in softwater lakes across eastern North America and western Europe. Using long-term contemporary and palaeo-environmental field data, we show that this is precipitating a dramatic change in Canadian lakes: the replacement of previously dominant pelagic herbivores (Ca-rich Daphnia species) by Holopedium glacialis, a jelly-clad, Ca-poor competitor. In some lakes, this transformation is being facilitated by increases in macro-invertebrate predation, both from native (Chaoborus spp.) and introduced (Bythotrephes longimanus) zooplanktivores, to which Holopedium, with its jelly coat, is relatively invulnerable. Greater representation by Holopedium within cladoceran zooplankton communities will reduce nutrient transfer through food webs, given their lower phosphorus content relative to daphniids, and greater absolute abundances may pose long-term problems to water users. The dominance of jelly-clad zooplankton will likely persist while lakewater Ca levels remain low.


Home language and societal language skills in second-generation bilingual adults.
Research aims were (a) to test competing predictions regarding the levels of heritage and societal language proficiency among young adults who experienced early exposure to both languages, and (b) to identify sources of individual differences in degree of bilingualism. Participants comprised 65 Spanish-English bilinguals who reported using both languages on a weekly basis, 25 native English monolinguals, and 25 native Spanish monolinguals. Language and literacy skills were assessed with a battery of standardized and research-based assessments. Degree of bilingualism was calculated for the bilingual participants. Paired sample t-tests compared the bilinguals' skills in English to their skills in Spanish. Hierarchical regression evaluated factors related to their degree of bilingualism. Independent sample t-tests compared bilinguals' single-language skills to monolinguals. The bilinguals' English skills were stronger than their Spanish skills on every measure. Thus, degree of bilingualism was largely a function of level of Spanish skill and was associated with concurrent Spanish exposure. Bilinguals' English skills were not different from the monolinguals except in speed of lexical access. The bilinguals' Spanish skills were significantly lower than the Spanish monolinguals on every measure except in accuracy judgments for grammatically correct sentences. Previous studies of bilingual adults have focused on sequential bilinguals and previous studies of heritage language speakers have focused on their grammatical skills. This is the first study, to our knowledge, to assess a wide range of functionally relevant skills in adults with early exposure to a heritage and societal language. These findings demonstrate that early exposure to and continued use of a home language does not interfere with the achievement of societal language and literacy skills, while also demonstrating that even a widely and frequently used home language may not be acquired to the same skill level as a societal language used in school.


Treatment of acute asthma. Lack of therapeutic benefit and increase of the toxicity from aminophylline given in addition to high doses of salbutamol delivered by metered-dose inhaler with a spacer.
We conducted a randomized, double-blind, placebo-controlled study to determine if intravenous aminophylline adds any benefit to high doses of inhaled salbutamol in patients who presented for treatment of acute asthma. We studied 94 patients (mean age, 35.6 +/- 11.2 years) with moderate to severe acute asthma. All patients received therapy with salbutamol delivered with metered-dose inhaler (MDI) into a spacer device (Volumatic) in four puffs (400 micrograms) at 10-min interval, and intravenous hydrocortisone (500 mg). Patients were randomly assigned to receive either a loading dose of intravenous aminophylline followed by a routine infusion (n = 45) or an equal volume of placebo as a loading dose and infusion (n = 49). The two groups showed no differences in measurements of peak expiratory flow, FEV1, and FVC at baseline and at the end of treatment. However, the patients treated with aminophylline had significantly more adverse effects (p < 0.05). There were no differences in the final mean dose of salbutamol (6.3 +/- 44.5 mg for the placebo group and 5.8 +/- 4.2 mg for the aminophylline group), hospital admission rate (10.2 percent for the placebo group and 9.0 percent for the aminophylline group), and mean duration of Emergency Department treatment (2.5 +/- 1.83 h for the placebo group and 2.37 +/- 1.75 h for the aminophylline group). The results were similar when the patients were divided in accord with the degree of respiratory obstruction (baseline FEV1 < 30 percent of predicted) and theophylline level at 30 min of treatment (placebo group patients with theophylline level < 10 mg/L vs aminophylline group patients with theophylline level > or = 10 mg/L). We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled salbutamol in the treatment of acute exacerbations of asthma.


Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents.
Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional ('hot') and cognitive control ('cold') neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of 'hot' emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of 'cold' cognition.


[Methylation and protein expression of RASSF2 in prostate cancer].
To investigate the role of the epigenetic inactivation of Ras association domain family 2 (RASSF2) in the occurrence and development of prostate cancer by detecting the methylation and protein expression of RASSF2 in the tissues of prostate cancer and prostatic hyperplasia. We obtained genome DNA from 30 formalin-fixed paraffin-embedded specimens of prostate cancer (experimental group) and another 30 of prostatic hyperplasia (control group). We detected the methylation of RASSF2 by methylation-specific PCR (MSP) and its protein expression by immunohistochemistry. The rates of RASSF2 promoter hypermethylation and the absence of its protein expression were 66.7% (20/30) and 70.0% (21/30) respectively in the experimental group, significantly higher than 6.7% (2/30) and 3.3% (1/30) in the control group (P < 0.05). The promoter hypermethylation of RASSF2 was significantly correlated with the absence of its protein expression (P < 0.05). The epigenetic inactivation of RASSF2 is involved in the occurrence of prostate cancer, and is expected to be a target of molecular diagnosis and treatment of prostate cancer.


Morphological investigation of neurofibrillary tangles in Alzheimer's disease.
There are two types of neurofibrillary tangles, namely, a twisted tubule and a straight or uniform tubule in the same cell in the brain with Alzheimer's disease. However, in some parts of the same fibril, both the twisted and straight tubules clearly could be seen as a continuation of each other. This finding suggests that both of the tubules have a deep relation to each other, especially at the molecular level. This might also suggest the possibility of both tubules which mutually transform into each other.


[Detection of interferon-induced transmembrane-1 gene expression for clinical diagnosis of colorectal cancer].
To investigate the expression of the interferon-induced transmembrane-1 (IFITM1) gene in colorectal cancer (CRC) tissue and the serum anti-IFITM1 antibody responses of the patients and assess their value in clinical diagnosis of CRC. Semi-quantitative RT-PCR was performed to detect IFITM1 mRNA expression in the specimens of normal colonic mucosa, CRC tissue, inflammatory polyps, adenomatous polyps, gastric cancer, esophageal carcinoma and liver cancer tissues. Serum samples were collected from the patients to detect anti-IFITM1 antibody responses using Western blotting. The clinicopathological features of the carcinoma expressing IFITM1 gene were analyzed. IFITM1 mRNA was expressed in 47.4 % (18/38) of the CRC specimens, a rate significantly higher than that in adenomatous polyps [15% (3/20)] and gastric cancer [4.8% (1/21)]; no obvious IFITM1 expression was found in normal colonic mucosa, inflammatory polyp, esophageal carcinoma or liver cancer tissues (P<0.001 or P<0.05). IFITM1 mRNA was strongly expressed in CRC at the expression level of 0.8048-/+0.2273, which was significantly higher than that in adenomatous polyps (0.4447-/+0.0989, P<0.001). No anti-IFITM1 antibody response was detected in healthy human sera, but in the CRC patients, the serum antibody response was detected at the rate of 36.8% (14/38), significantly higher than the rate of 9.5% (2/21) in gastric cancer (P<0.05). No antibody response was detected in esophageal carcinoma, liver cancer, inflammatory polyp or adenomatous polyps. Most of the IFITM1-expressing CRC had a diameter exceeding 5 cm, often invading the serous membrane with metastasis to the lymph nodes and the distant organs; these tumors were identified mostly as well-differentiated adenocarcinoma in Dukes stage C or D. IFITM1 gene may play an important role in the pathogenesis, development and metastasis of CRC, and may serve as a potential biomarker for clinical diagnosis of CRC.


Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.
Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development.


Gap junction coupling confers isopotentiality on astrocyte syncytium.
Astrocytes are extensively coupled through gap junctions into a syncytium. However, the basic role of this major brain network remains largely unknown. Using electrophysiological and computational modeling methods, we demonstrate that the membrane potential (VM) of an individual astrocyte in a hippocampal syncytium, but not in a single, freshly isolated cell preparation, can be well-maintained at quasi-physiological levels when recorded with reduced or K(+) free pipette solutions that alter the K(+) equilibrium potential to non-physiological voltages. We show that an astrocyte's associated syncytium provides powerful electrical coupling, together with ionic coupling at a lesser extent, that equalizes the astrocyte's VM to levels comparable to its neighbors. Functionally, this minimizes VM depolarization attributable to elevated levels of local extracellular K(+) and thereby maintains a sustained driving force for highly efficient K(+) uptake. Thus, gap junction coupling functions to achieve isopotentiality in astrocytic networks, whereby a constant extracellular environment can be powerfully maintained for crucial functions of neural circuits.


Cognitive dysfunction and depression during treatment with interferon-alpha and chemotherapy.
Trials with interferon-alpha (IFN-alpha) have provided contradictory findings regarding the presence of cognitive side effects. The development of depression in some patients also raises questions about whether cognitive dysfunction might be secondary to an organic, interferon-induced mood disorder. Thirty patients with chronic myelogenous leukemia were examined before and during treatment with IFN-alpha alone or IFN-alpha and chemotherapy. Increased depressive symptoms and declines in information processing and executive functions were observed, but depression alone could not account for cognitive dysfunction. There was some evidence suggesting that exposure to chemotherapy and higher cumulative IFN-alpha dose may contribute to cognitive impairment.


[Increasing incidence of femoral neck fractures in Alborg].
The object of this investigation was to analyse the frequency of medial and pertrochanteric fractures of the femoral neck and to calculate the future number. During the period 1976-1988, 3,099 patients aged over 50 years were admitted to hospital with fractures of the femoral neck. 60% were medial femoral neck fractures. The sex ratio women:men was 2.94. The median age rose from 78 to 80 years. The annual number of fractures rose from 151 to 344. The population over 50 years of age had increased by 5.4%. The incidence increased from 3.31 per 1,000 in 1976 to 7.15 per 1,000 in 1988. By means of linear regression, the frequency in year 2010 was calculated to be 14.5 per 1,000 and the number of fractures 794. During the course of the coming 17 years, doubling of the number of medial and pertrochanteric femoral neck fractures may be anticipated, provided linear increase in the frequency occurs.


Cephalosporins. I. Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain.
Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain have been prepared by nucleophilic substitution of 7-aminocephalosporanic acid with appropriate azine thiols followed by 7-N-acylation with phenylglycine by the mixed anhydride method. Seventeen thiols of non-substituted or substituted pyridines, pyridazines, pyrimidines, pyrazines and triazines were used as the S-nucleophiles. In general, pyridazine thiols gave cephalosporins processing good antimicrobial activity against both gram-positive and gram-negative bacteria. Among them 6-hydroxypyridazine-3-thiol gave the most active compound of this series, BB-S 118 (1f), which was significantly more active than cephalexin and cephaloglycin in vitro against gram-positive and gram negative bacteria.


[Steinert's disease (dystrophia myotonica). General review].
By comments of 9 tables the main clinical and genetic features of myotonic dystrophy are recalled. Due to a most variable penetrance and expressivity, the recognition of the adult form of this autosomal dominant disease can be difficult. Congenital myotonic dystrophy is a serious disease which represents a major genetic risk for the heterozygous women, which are often very slightly affected or even not aware of their disorder. For them, prenatal diagnosis is fully justified and now possible with a small risk of error by determination of DNA polymorphism. Preclinical detection in young adults can also be improved by this new method.


Virulence characteristics and the molecular epidemiology of enteroaggregative Escherichia coli isolates from travellers to developing countries.
Enteroaggregative Escherichia coli (EAEC) is associated with diarrhoea among travellers to developing countries. EAEC virulence properties predisposing to illness are not clear. Sixty-four EAEC strains identified by a HEp-2 cell assay and isolated from faecal samples from US and European travellers to developing countries were studied for the prevalence of 11 putative virulence genes by PCR: 49 EAEC strains from adults with acute diarrhoea and 15 EAEC strains from adults without diarrhoea. E. coli strains from the stools of healthy travellers to the same region were used as controls. EAEC carrying aggR, aap, astA and set1A were identified individually more often in the stools of subjects with diarrhoea compared with those without diarrhoea (P<0.05). EAEC isolates with two or three of these genes were associated with diarrhoea compared with EAEC isolates without the presence of these genes (P<0.05). Subjects with diarrhoea who shed EAEC isolates positive for these genes were more likely than subjects shedding EAEC negative for these genes to pass stools with gross mucus (57 vs 14 %) and faecal leukocytes (40 vs 7 %) (P<0.05). This study shows the heterogeneity of gene profiles of EAEC strains found in the stools of international travellers and suggests that the presence of aggR, aap, astA or set1A, the number of genes present and stool characteristics may be markers for more virulent EAEC strains.


Dietary Inflammatory Index and Biomarkers of Lipoprotein Metabolism, Inflammation and Glucose Homeostasis in Adults.
Accumulating evidence identifies diet and inflammation as potential mechanisms contributing to cardiometabolic risk. However, inconsistent reports regarding dietary inflammatory potential, biomarkers of cardiometabolic health and metabolic syndrome (MetS) risk exist. Our objective was to examine the relationships between a food frequency questionnaire (FFQ)-derived dietary inflammatory index (DII®), biomarkers of lipoprotein metabolism, inflammation and glucose homeostasis and MetS risk in a cross-sectional sample of 1992 adults. Energy-adjusted DII (E-DII) scores derived from an FFQ were calculated. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance (NMR) spectroscopy. Serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were determined. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Our data indicate that a more pro-inflammatory diet, reflected by higher E-DII scores, was associated with potentially pro-atherogenic lipoprotein profiles characterised by increased numbers of large very low density lipoprotein (VLDL), small dense low density lipoprotein (LDL) and high density lipoprotein (HDL) particles and less large LDL and HDL particles (all p < 0.001). Inflammatory profiling identified a range of adverse phenotypes among those with higher E-DII scores, including higher complement component C3 (C3), C-reactive protein (CRP), (both p < 0.05), interleukin 6 (IL-6) and tumour necrosis factor (TNF)-α concentrations, higher WBC counts and neutrophil to lymphocyte ratio (NLR) and lower adiponectin levels (all p < 0.001). MetS risk was increased among those with higher E-DII scores (OR 1.37, 95% CI (1.01, 1.88), p < 0.05), after adjusting for potential confounders. In conclusion, habitual intake of a more pro-inflammatory diet is associated with unfavourable lipoprotein and inflammatory profiles and increased MetS risk.


On the origins of a crowded cytoplasm.
Contemporary cells show a highly crowded macromolecular content, the processes which originated this state being largely unknown. We propose that a driving force leading to the crowded cellular state could be the increase in growth rate produced by an enhanced cytoplasmic protein concentration. Briefly, in a diluted scenario, an increase in protein concentration has two opposing effects on growth rate. The favorable effect is the increase in the activity per unit volume of the component proteins and the disadvantageous effect is the concomitant increase in the protein mass per unit volume which has to be produced. In this work we show that the first effect is quantitatively more important, resulting in an overall increase in growth rate. This result was obtained with a model of E. coli and using nonmechanistic physiological arguments. The proposed driving force operates even at low protein concentrations, where the nonspecific interactions of macromolecular crowding are not significant, and could be as ancient as the first protocells. Experimental measurement of this cytoplasmic protein concentration effect in present organisms is hindered by the prevailing nonspecific interactions, product of long-term evolution. However, chemical/biochemical systems, built up to mimic properties of living cells, could be an adequate tool to test this effect.


Six-Step Total Synthesis of Azaspirene.
The total synthesis of (±)-azaspirene (1) was achieved in a total of six steps from commercially available materials. Keys to the conciseness of our synthetic approach were the effective γ-lactam formation from linear precursor 36 and successful tandem epoxidations of γ-lactam 34 to afford α,β-epoxy-γ-hydroxy-γ-lactam intermediate 14. While our streamlined synthesis of azaspirene (1) sought inspiration from its biogenetic hypothesis, experimentally observed chemical reactivity of biosynthetically relevant precursors conversely provides insights to the biological origin of this natural product.


Effects of puerarin on the pharmacokinetics of astragaloside IV in rats and its potential mechanism.
Context: Puerarin and astragaloside IV (AS-IV) are sometimes used together for the treatment of disease in Chinese clinics, however, the drug-drug interaction between puerarin and AS-IV is still unknown.Objective: This study investigates the effects of puerarin on the pharmacokinetics of astragaloside IV in rats and clarifies its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of astragaloside IV (20 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of puerarin (100 mg/kg/day for 7 days) were investigated. The effects of puerarin on the transport and metabolic stability of AS-IV were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 48.58 ± 7.26 to 72.71 ± 0.62 ng/mL), and decrease the oral clearance (from 47.5 ± 8.91 to 27.15 ± 9.27 L/h/kg) of AS-IV. The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of astragaloside IV from 1.89 to 1.26, and the intrinsic clearance rate of astragaloside IV was decreased by the pre-treatment with puerarin (34.8 ± 2.9 vs. 41.5 ± 3.8 μL/min/mg protein).Discussion and conclusions: These results indicated that puerarin could significantly change the pharmacokinetic profiles of astragaloside IV, via increasing the absorption of astragaloside IV or inhibiting the metabolism of astragaloside IV in rats.


Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.
To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O2-) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF2α receptor antagonist) or SQ29584 [PGH2/thromboxane TXA2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O2- and hydrogen peroxide (H2O2) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature.


Pax-6, a murine paired box gene, is expressed in the developing CNS.
A multigene family of paired-box-containing genes (Pax genes) has been identified in the mouse. In this report, we describe the expression pattern of Pax-6 during embryogenesis and the isolation of cDNA clones spanning the entire coding region. The Pax-6 protein consists of 422 amino acids as deduced from the longest open reading frame and contains, in addition to the paired domain, a paired-type homeodomain. Beginning with day 8 of gestation, Pax-6 is expressed in discrete regions of the forebrain and the hindbrain. In the neural tube, expression is mainly confined to mitotic active cells in the ventral ventricular zone along the entire anteroposterior axis starting at day 8.5 of development. Pax-6 is also expressed in the developing eye, the pituitary and the nasal epithelium.


Felodipine in primary pulmonary hypertension. Report of two cases.
Two women with primary pulmonary hypertension were treated with felodipine, a vasodilating agent. A marked reduction in pulmonary artery pressure was noted in one, whereas the other showed no reduction in pressure but an increase in blood flow and a decrease in pulmonary vascular resistance.


[The epidemiology of medical errors: a few issues in methodology].
Epidemiological research is needed to determine how many medical errors are made in hospitals. An estimation of error risk requires knowledge of the number of errors made and the total number of patients treated. But how do we define the term 'error'? The outcome of a medical intervention alone is insufficient; the entire treatment process has to be taken into account. For the estimation of error, two different approaches are available: retrospective chart review or prospective ethnographic observation. Both methods should account for processes and outcomes. Both methods have their limitations and can produce measurement errors. In particular, the low reproducibility of the determination of error is worrisome. To achieve safer health care, emphasis should be placed on control of processes, rather than outcomes.


Thermal inactivation kinetics of Rabdosia serra (Maxim.) Hara leaf peroxidase and polyphenol oxidase and comparative evaluation of drying methods on leaf phenolic profile and bioactivities.
Inactivation kinetics of peroxidase and polyphenol oxidase in fresh Rabdosia serra leaf were determined by hot water and steam blanching. Activation energy (52.30 kJ mol(-1)) of polyphenol oxidase inactivation was higher than that (20.15 kJ mol(-1)) of peroxidase. Water blanching at 90 °C or steam blanching at 100 °C for 90 s was recommended as the preliminary treatment for the retention of phenolics. Moreover, comparative evaluation of drying methods on the phenolics profiles and bioactivities of R. serra leaf were conducted. The results indicated that only intact leaf after freeze drying retained the initial quality. The sun- and air-dried leaves possessed identical phenolic profiles. The homogenised leaf (after freeze-drying) possessed a lower level of phenolics due to enzymatic degradation. Good antioxidant activities were detected for the sun- and air-dried leaves. There was insignificant difference in anti-tyrosinase and anti-α-glucosidase activities among sun-, air-, and freeze-dried leaves.


Regulation of pH in rat brain synaptosomes. I. Role of sodium, bicarbonate, and potassium.
1. We investigated the regulation of intracellular pH (pHi) in rat brain isolated nerve terminals (synaptosomes), using fluorescence pH indicators and time-resolved fluorescence spectroscopy. 2. The resting pHi was not significantly affected by the presence or absence of HCO3-. Removal of external Na+, in the absence or presence of HCO3- caused a rapid acidification of pHi. The recovery from acid loads was primarily due to the activity of the Na+/H+ exchanger, confirming the relevance of this transport system in synaptosomes. 3. Our data revealed that in synaptosomes the activity of the Na+/H+ exchanger was not regulated by either protein kinase C or kinase A. In contrast, Ca2+ played an important role in the regulation of Na+/H+ exchanger. This was supported by the observation that 4Br-A23187 induced a Na(+)-dependent alkalinization of the resting pHi and greatly enhanced the initial rate and the degree of the recovery from acid loads. 4. In most eukaryotic cells, HCO3(-)-based transport mechanisms play an important role in pHi regulation. In synaptosomes, however, HCO3- transport is not significantly involved in pHi regulation, because the presence or absence of HCO3- does not affect resting pHi nor the rate of pHi recovery to acid loads. Further studies to address the role of Cl- and HCO3- in pHi regulation in synaptosomes are discussed in the companion paper. 5. Increasing the concentration of Ko+ also resulted in a rise of steady-state pHi by a processes that is Ca2+ and HCO3- independent. This alkalinization could be due to either K+/H+ exchanger activity, K(+)-induced depolarization, reduction of delta microH+, or a direct reduction of delta microK+. Calculated H+ driving forces suggest that the reduction in the inwardly directed H+ leak is sufficient to explain this K(+)-induced alkalinization because it changes the delta microH+ by virtue of setting the membrane potential difference (Em) to the K+ equilibrium potential (EK+).


Critical examination of resilience and resistance in african american families: Adaptive capacities to navigate toxic oppressive upstream waters.
African American families navigate not only everyday stressors and adversities but also unique sociocultural stressors (e.g., "toxic upstream waters" like oppression). These adverse conditions are consequences of the historical vestiges of slavery and Jim Crow laws, often manifested as inequities in wealth, housing, wages, employment, access to healthcare, and quality education. Despite these challenges, African American families have developed resilience using strength-based adaptive coping strategies, to some extent, to filter these waters. To advance the field of resilience research, we focused on the following questions: (1) what constitutes positive responses to adversity?; (2) how is resilience defined conceptually and measured operationally?; (3) how has the field of resilience evolved?; (4) who defines what, when, and how responses are manifestations of resilience, instead of, for example, resistance? How can resistance, which at times leads to positive adaptations, be incorporated into the study of resilience?; and (5) are there case examples that demonstrate ways to address structural oppression and the pernicious effects of racism through system-level interventions, thereby changing environmental situations that sustain toxic waters requiring acts of resilience to survive and thrive? We end by exploring how a re-conceptualization of resilience requires a paradigm shift and new methodological approaches to understand ways in which preventive interventions move beyond focusing on families' capacity to navigate oppression and target systems and structures that maintain these toxic waters.


Effects of dehydration methods on quality characteristics of yellow passion fruit co-products.
The production and processing of fruits generate a large amount of residues, which are usually disposed of or under-used, representing losses of raw material and energy. The present paper investigates the effect of four dehydration techniques (convective, infrared, microwave and freeze-drying) on yellow passion fruit (Passiflora edulis f. flavicarpa) co-products and the influence of the main variables on moisture removal and bioactive compounds. The compounds analyzed were total phenolics, total flavonoids, ascorbic acid and pectin. The content of phenolics and flavonoids increased after dehydration in all techniques investigated and the process temperatures directly affected the ascorbic acid content. Microwave dehydration showed the best results for most bioactive compounds analyzed, if performed in suitable process conditions. However, the highest levels of pectin content were obtained by freeze-drying and convective dehydration. This study reinforces the importance of the adequate use of passion fruit co-products due to the high levels of bioactive compounds in this material. Microwave dehydration presented the best results, which indicates the potential use of this technique for a better exploitation of fruit co-products. Larger quantities of pectin were extracted from samples dehydrated through methodologies with long-time process and low temperatures, such as convective drying and freeze-drying. © 2017 Society of Chemical Industry.


A C57BL/6J Fancg-KO Mouse Model Generated by CRISPR/Cas9 Partially Captures the Human Phenotype.
Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in the repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in the interpretation of genotype-related phenotype. We created a Fancg-KO (KO) mouse model using CRISPR/Cas9 to exclude these confounders. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. The intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting the loss of FANCG can be embryonically lethal. KO mice displayed infertility and hypogonadism, but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to the crosslinking agents cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. The reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. This project provides a new, genetically, and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.


Using ergodicity of chaotic systems for improving the global properties of the delayed feedback control method.
A modified delayed feedback control algorithm with the improved global properties is proposed. The modification is based on the ergodic features of chaotic systems. We do not perturb the system until its state approaches a desired unstable periodic orbit and then we activate the delayed feedback control force. To evaluate the closeness of the system state to the target orbit, a special algorithm is devised. For continuous-time systems, it can be implemented by means of a simple low-pass filter. An additional low-pass filter can be used for selection of the particular orbit from several unstable orbits of the same period.