Necessity of adjuvants for inducing effective antibody response to zona pellucida antigens.
Rhesus monkeys evoked a vigorous antibody response to a single heteroimmunization dose of zona pellucida antigens, when these were administered along with complete Freund's adjuvant. The antisera recognized all the three major porcine zona glycoprotein families and the animals were rendered amenorrheic after such immunization. Monkeys immunized with zona without adjuvant, however, failed to show any anti-zona antibody response and had normal menstrual cycles. Zona pellucida glycoproteins are thus not effective immunogens unless administered along with a powerful adjuvant.


Dietary supplements: altered coagulation and effects on bruising.
Patient use of dietary supplements that alter coagulation or have an effect on bruising is becoming increasingly common. To identify and describe dietary supplements that alter coagulation or are reported to alter bruising during and after surgical procedures. The MEDLINE, Cochrane Collaboration, and International Bibliographic Information on Dietary Supplements databases were searched for articles using the search words "bruising," "bleeding," "coagulation," "hemostasis," "herbal medicine," "alternative medicine," and "dietary supplement." Additional sources were obtained from manual searches of recent journal articles. In vivo and in vitro evidence supports the notion that many dietary supplements alter coagulation. Limited evidence is available to support anecdotal claims of diminished postoperative bruising after the use of dietary supplements. Surgeons should be aware that many of their patients are taking dietary supplements that may alter coagulation. Because most patients will not readily volunteer this information, specific steps should be taken to obtain it prior to more extensive surgical procedures.


Biogenesis of Escherichia coli DMSO Reductase: A Network of Participants for Protein Folding and Complex Enzyme Maturation.
Protein folding and structure have been of interest since the dawn of protein chemistry. Following translation from the ribosome, a protein must go through various steps to become a functional member of the cellular society. Every protein has a unique function in the cell and is classified on this basis. Proteins that are involved in cellular respiration are the bioenergetic workhorses of the cell. Bacteria are resilient organisms that can survive in diverse environments by fine tuning these workhorses. One class of proteins that allow survival under anoxic conditions are anaerobic respiratory oxidoreductases, which utilize many different compounds other than oxygen as its final electron acceptor. Dimethyl sulfoxide (DMSO) is one such compound. Respiration using DMSO as a final electron acceptor is performed by DMSO reductase, converting it to dimethyl sulfide in the process. Microbial respiration using DMSO is reviewed in detail by McCrindle et al. (Adv Microb Physiol 50:147-198, 2005). In this chapter, we discuss the biogenesis of DMSO reductase as an example of the participant network for complex iron-sulfur molybdoenzyme maturation pathways.


Triton X-100 as a specific inhibitor of the mammalian NADH-ubiquinone oxidoreductase (Complex I).
Triton X-100 inhibits the NADH oxidase and rotenone-sensitive NADH-Q1 reductase activities of bovine heart submitochondrial particles (SMP) with an apparent Ki of 1x10-5 M (pH 8.0, 25 degrees C). The NADH-hexammineruthenium reductase, succinate oxidase, and the respiratory control ratio with succinate as the substrate in tightly coupled SMP are not affected at the inhibitor concentrations below 0.15 mM. The succinate-supported aerobic reverse electron transfer is less sensitive to the inhibitor (Ki=5x10-5 M) than NADH oxidase. Similar to rotenone, limited concentrations of Triton X-100 increase the steady-state level of NAD+ reduction when the nucleotide is added to tightly coupled SMP oxidizing succinate aerobically. Also similar to rotenone, Triton X-100 partially protects Complex I against the thermally induced deactivation and partially activates the thermally deactivated enzyme. The rate of the NADH oxidase inhibition by rotenone is drastically decreased in the presence of Triton X-100 which indicates a competition between these two inhibitors for a common specific binding site. In contrast to rotenone, the inhibitory effect of Triton X-100 is instantly reversed upon dilution of the reaction mixture. The NADH-Q1 reductase activity of SMP is inhibited non-competitively by added Q1 whereas a simple competition between Q1 and the inhibitor is seen for isolated Complex I. The results obtained show that Triton X-100 is a specific inhibitor of the ubiquinone reduction by Complex I and are in accord with our previous findings which suggest that different reaction pathways operate in the forward and reverse electron transfer at this segment of the mammalian respiratory chain.


Ring opening of nonactivated 2-(1-aminoalkyl) aziridines: unusual regio- and stereoselective C-2 and C-3 cleavage.
We have studied the ring opening of nonactivated amino aziridines 1 by water under acidic conditions. Depending on the acid used, amino aziridines are cleaved at C-3 or C-2 with high regioselectivity, and total stereoselectivity, affording chiral 2,3-diaminoalkan-1-ols 3 or 1,3-diaminoalkan-2-ols 4 in high yield.


Functional diversification of heat shock factors.
Heat shock transcription factors (HSFs) are widely known as master regulators of the heat shock response. In invertebrates, a single heat shock factor, HSF1, is responsible for the maintenance of protein homeostasis. In vertebrates, seven members of the HSF family have been identified, namely HSF1, HSF2, HSF3, HSF4, HSF5, HSFX, and HSFY, of which HSF1 and HSF2 are clearly associated with heat shock response, while HSF4 is involved in development. Other members of the family have not yet been studied as extensively. Besides their role in cellular proteostasis, HSFs influence a plethora of biological processes such as aging, development, cell proliferation, and cell differentiation, and they are implicated in several pathologies such as neurodegeneration and cancer. This is achieved by regulating the expression of a great variety of genes including chaperones. Here, we review our current knowledge on the function of HSF family members and important aspects that made possible the functional diversification of HSFs.


RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury.
Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.


Comorbidity defines asthmatic patients' risk of COVID-19 hospitalization: A global perspective.
The global epidemiology of asthma among patients with coronavirus disease 2019 (COVID-19) presents striking geographic differences, defining prevalence zones of high and low co-occurrence of asthma and COVID-19. We aimed to compare asthma prevalence among hospitalized patients with COVID-19 in major global hubs across the world by applying common inclusion criteria and definitions. We built a network of 6 academic hospitals in Stanford (Stanford University)/the United States; Frankfurt (Goethe University), Giessen (Justus Liebig University), and Marburg (Philipps University)/Germany; and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19. Asthmatic individuals were overrepresented among hospitalized patients with COVID-19 in Stanford and underrepresented in Moscow and Germany as compared with their prevalence among adults in the local community. Asthma prevalence was similar among patients hospitalized in an intensive care unit and patients hospitalized in other than an intensive care unit, which implied that the risk for development of severe COVID-19 was not higher among asthmatic patients. The numbers of males and comorbidities were higher among patients with COVID-19 in the Stanford cohort, and the most frequent comorbidities among these patients with asthma were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease. The observed disparity in COVID-19-associated risk among asthmatic patients across countries and continents is connected to the varying prevalence of underlying comorbidities, particularly chronic obstructive pulmonary disease.


Native and nonnative reactions in ethanolamine ammonia-lyase are actuated by different dynamics.
We address the contribution of select classes of solvent-coupled configurational fluctuations to the complex choreography involved in configurational and chemical steps in an enzyme by comparing native and nonnative reactions conducted at different protein internal sites. The low temperature, first-order kinetics of covalent bond rearrangement of the cryotrapped substrate radical in coenzyme B12-dependent ethanolamine ammonia-lyase (EAL) from Salmonella enterica display a kink, or increase in slope, of the Arrhenius plot with decreasing temperature. The event is associated with quenching of a select class of reaction-actuating collective fluctuations in the protein hydration layer. For comparison, a nonnative, radical reaction of the protein interior cysteine sulfhydryl group with hydrogen peroxide (H2O2) is introduced by cryotrapping EAL in an aqueous H2O2 eutectic system. The low-temperature aqueous H2O2 protein hydration and mesodomain solvent phases surrounding cryotrapped EAL are characterized by using TEMPOL spin probe electron paramagnetic resonance spectroscopy, including a freezing transition of the eutectic phase that orders the protein hydration layer. Kinetics of the cysteine-H2O2 reaction in the EAL protein interior are monitored by DEPMPO spin trapping of hydroxyl radical product. In contrast to the native reaction, the linear Arrhenius relation for the nonnative cysteine-H2O2 reaction is maintained through the solvent-protein ordering transition. The nonnative reaction is coupled to the generic local, incremental fluctuations that are intrinsic to globular proteins. The comparative approach supports the proposal that select coupled solvent-protein configurational fluctuations actuate the native reaction, and suggests that select dynamical coupling contributes to the degree of catalysis in enzymes.


Strong Electron-Deficient Polymers Lead to High Electron Mobility in Air and Their Morphology-Dependent Transport Behaviors.
Planar backbone, locked conformation, and low lowest unoccupied molecular orbital level provide polymer F4 BDOPV-2T with ultrahigh electron mobilities of up to 14.9 cm(2) V(-1) s(-1) and good air stability. It is found that the nonlinear transfer curves can be tuned to near-ideal ones by changing fabrication conditions, indicating that film morphology largely contributes to the nonlinear transfer curves in high-mobility conjugated polymers.


Antibiotic Use Among Hospitalized Patients in Africa: A Systematic Review of Point Prevalence Studies.
There is paucity of data describing the rate and quality indices of antibiotics used among hospitalized patients at continental level in Africa. This systematic review evaluated the pooled prevalence, indications, and types of antibiotics used in hospitals across Africa. Three electronic databases, PubMed, Scopus, and African Journals Online (AJOL), were searched using search terms. Point prevalence studies of antibiotic use in inpatient settings published in English language from January 2010 to November 2022 were considered for selection. Additional articles were identified by checking the reference list of selected articles. Of the 7254 articles identified from the databases, 28 eligible articles involving 28 studies were selected. Most of the studies were from Nigeria (n = 9), Ghana (n = 6), and Kenya (n = 4). Overall, the prevalence of antibiotic use among hospitalized patients ranged from 27.6 to 83.5% with higher prevalence in West Africa (51.4-83.5%) and North Africa (79.1%) compared to East Africa (27.6-73.7%) and South Africa (33.6-49.7%). The ICU (64.4-100%; n = 9 studies) and the pediatric medical ward (10.6-94.6%; n = 13 studies) had the highest prevalence of antibiotic use. Community-acquired infections (27.7-61.0%; n = 19 studies) and surgical antibiotic prophylaxis (SAP) (14.6-45.3%; n = 17 studies) were the most common indications for antibiotic use. The duration of SAP was more than 1 day in 66.7 to 100% of the cases. The most commonly prescribed antibiotics included ceftriaxone (7.4-51.7%; n = 14 studies), metronidazole (14.6-44.8%; n = 12 studies), gentamicin (n = 8 studies; range: 6.6-22.3%), and ampicillin (n = 6 studies; range: 6.0-29.2%). The access, watch, and reserved group of antibiotics accounted for 46.3-97.9%, 1.8-53.5%, and 0.0-5.0% of antibiotic prescriptions, respectively. The documentation of the reason for antibiotic prescription and date for stop/review ranged from 37.3 to 100% and 19.6 to 100%, respectively. The point prevalence of antibiotic use among hospitalized patients in Africa is relatively high and varied between the regions in the continent. The prevalence was higher in the ICU and pediatric medical ward compared to the other wards. Antibiotics were most commonly prescribed for community-acquired infections and for SAP with ceftriaxone, metronidazole, and gentamicin being the most common antibiotics prescribed. Antibiotic stewardship is recommended to address excessive use of SAP and to reduce high rate of antibiotic prescribing in the ICU and pediatric ward.


Relationship of time since childbirth and other pregnancy factors to premenopausal breast cancer prognosis.
To investigate the influence of time since childbirth and other pregnancy factors on the prognosis of premenopausal breast cancer. Women who delivered an infant in Nova Scotia, Canada, between 1980 and 2001 were identified from a provincial perinatal database and linked to the Nova Scotia Cancer Registry to determine primary breast cancer diagnoses among women aged younger than 50 years. Relative risks and Cox proportional hazards ratios were calculated to quantify the relationship of time from childbirth to diagnosis and other pregnancy factors to the extent of disease at diagnosis and on survival after breast cancer diagnosis. Of the 123,323 women who delivered an infant during the study period, 716 women were diagnosed with invasive breast cancer. Women with less than 5 years between their last delivery and diagnosis were more likely to be diagnosed with later-stage disease and had poorer survival even after adjusting for stage of disease (less than 2 years, adjusted hazards ratio 2.1, 95% confidence interval 1.2-3.9; 2-4 years, hazards ratio 1.6, 95% confidence interval 0.9-2.8) compared with women with 5 years or more. For every 13 women with less than 2 years between delivery and diagnosis, one excess death will occur, compared with women with 5 or more years between delivery and diagnosis. A time interval of less than 2 years (and 2-4 years) between childbirth and breast cancer diagnosis worsens the prognosis in a dose-response fashion. Clinicians should be aware of these findings when examining women in the first 5 years after a delivery. II.


Hierarchical change-point regression models including random effects to estimate empirical critical loads for nitrogen using Bayesian Regression Models (brms) and JAGS.
The concept of critical loads is used in the framework of the Convention on Long-range Transboundary Air Pollution (UNECE) to define thresholds below which no damaging effects on habitats occur based on the latest scientific knowledge. Change-point regression models applied in a Bayesian framework are useful statistical tools to estimate critical empirical loads. While hierarchical study designs are common in ecological research, previous methods to estimate critical loads using change-point regression did not allow to analyse data collected under such a design. This method update provides an implementation of hierarchical data structure by including random effects such as study sites or as in this example tree species within the Bayesian approach of change-point regression models using two different approaches. The example data set is an European wide gradient study of the impact of climate change and air pollution on forest tree health assessed by foliar nutrient status of nitrogen (N) to phosphorus (P) from 10 different conifer tree species originated from 88 forest sites and 9 countries covering 22 years (1995-2017). Both modelling approaches using JAGS and Bayesian Regression Models using 'Stan' (brms) resulted in reasonable and similar estimations of the critical empirical load for nitrogen (CLempN) for temperate forests. These methodological examples of using different approaches of Bayesian change-point regression models dealing with random effects could prove useful to infer CLempN for other ecosystems and long-term data sets.•Hierarchical change-point regression models are suitable for estimating critical empirical loads.•The Bayesian framework of these models provides the inclusion of the current critical load and various confounding or modifying variables.•Here we present two ways of implementing hierarchical data sets in Bayesian change-point regression models using JAGS and brms.


Perforating Peripheral Ulcerative Keratitis in Syphilis.
To present a case of peripheral ulcerative keratitis with perforation in the setting of syphilis. A single observational case report in urban USA. A patient with multiple sexual partners presented with bilateral peripheral ulcerative keratitis, unilateral corneal perforation, and a pustular rash. Workup was positive for syphilis as well as HSV, HIV, and multiple autoantibody tests. Findings improved after treatment for syphilis. Bilateral peripheral ulcerative keratitis in syphilis has been reported in one prior case. However, corneal perforation in the setting of syphilis infection has not, to our knowledge, been reported previously.


Capture and allocation of nitrogen byQuercus douglasii seedlings in competition with annual and perennial grasses.
The spatial overlap of woody plant root systems and that of annual or perennial grasses promotes competition for soil-derived resources. In this study we examined competition for soil nitrogen between blue oak seedlings and either the annual grassBromus mollis or the perennial grassStipa pulchra under controlled outdoor conditions. Short-term nitrogen competition was quantified by injecting15N at 30 cm depth in a plane horizontal to oak seedling roots and that of their neighbors, and calculating15N uptake rates, pool sizes and15N allocation patterns 24 h after labelling. Simultaneously, integrative nitrogen competition was quantified by examining total nitrogen capture, total nitrogen pools and total nitrogen allocation.Stipa neighbors reduced inorganic soil nitrogen content to a greater extent than didBromus plants. Blue oak seedlings responded to lower soil nitrogen content by allocating lower amounts of nitrogen per unit of biomass producing higher root length densities and reducing the nitrogen content of root tissue. In addition, blue oak seedlings growing with the perennial grass exhibited greater rates of15N uptake, on a root mass basis, compensating for higher soil nitrogen competition inStipa neighborhoods. Our findings suggest that while oak seedlings have lower rates of nitrogen capture than herbaceous neighbors, oak seedlings exhibit significant changes in nitrogen allocation and nitrogen uptake rates which may offset the competitive effect annual or perennial grasses have on soil nitrogen content.


Ruthenium catalyzed hydroaminoalkylation of isoprene via transfer hydrogenation: byproduct-free prenylation of hydantoins.
The ruthenium catalyst derived from Ru3(CO)12 and triphos [Ph2P(CH2CH2PPh2)2] promotes the direct C-C coupling of isoprene with aryl substituted hydantoins 1a–1f at the diene C4-position to furnish products of n-prenylation 2a–2f. A mechanism involving hydantoin dehydrogenation followed by diene-imine oxidative coupling to furnish a transient aza-ruthencyclopentene is proposed.


Photoinhibition in vivo of photosystem II reactions during development of the photosystems of wheat seedlings.
Photoinhibition of O2 evolution and reactions leading to millisecond-delayed light emission (ms-DLE) of chlorophyll by illumination of leaves with excess white light were investigated in wheat seedlings greened for different times in a special chamber with constant conditions (20 degrees C; CO2 and humidity). A sharp reduction in initial and steady state rates of O2 evolution and in the intensity of different components of ms-DLE under excess light on the stage of lag-phase of chlorophyll biosynthesis (4-6h of greening) were observed. An increasing stability of the oxygen-evolving process and ms-DLE of chlorophyll during formation of the thylakoid membrane photosystems (12-24 h of greening) was shown. Rifampicin did not influence the stability of oxygen evolution whereas cycloheximide led to the intensification of photoinhibition of the initial and steady-state rates of oxygen evolution under the inhibitory light action. The early stages of photosystems formation during short time of greening of etiolated seedlings were more sensitive to the action of inhibitory light, possibly due to a weak interaction of the oxygen-evolving system components and connection with reaction centers of Photosystem II.


Altered functional connectivity associated with cognitive impairment in neuromyelitis optica spectrum disorder.
Cognitive impairment is one of the common symptoms in patients with neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism remains unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to reveal the patterns of brain activity in patients with different cognitive states. Accordingly, this study investigated functional connectivity (FC) abnormalities within and between the main cognitive networks in cognitively impaired (CI) patients with NMOSD and their correlations with cognitive performance. Thirty-four patients with NMOSD and 39 healthy controls (HC) were included. Neuropsychological evaluations and rs-fMRI scanning were performed. Patients were classified as CI (n = 16) or cognitively preserved (CP; n = 18) according to neuropsychological evaluations. Seven components representing six main cognitive networks were selected by group independent component analysis. The differences in inter- and intranetwork FC among CI, CP, and HC groups were assessed. The correlation between FC values and neuropsychological data in NMOSD was calculated. The CI group showed decreased intranetwork connectivity in the posterior default mode network (pDMN) compared with the HC group (P < 0.05, GRF corrected), and decreased internetwork connectivity between the salience network (SN) and pDMN, and between the SN and right frontoparietal network (rFPN) compared with CP and HC groups. The altered FC values were significantly correlated with cognitive performance in the whole NMOSD group. The disconnection within the pDMN and between the SN and pDMN or rFPN might suggest the neural substrates underlying cognitive impairment in NMOSD.


Maximizing Thread Usage for Facial Rejuvenation: A Preliminary Patient Study.
Surgical facial rejuvenation techniques with thread lifting have gained popularity. To effectively rejuvenate an aging face, it is necessary to perform both soft tissue envelop repositioning and volume restoration procedures. With the trend toward less invasive techniques and long-lasting results with minimal complications, many surgeons have continued changing the techniques. In the present study, we developed the 4 M (Multi-target, Multi-vector, Multi-layer, Multi-material) thread lift technique for long-lasting results. A prospective study was conducted on 73 patients who underwent the 4 M thread lifting procedure between January 2016 and February 2018. To evaluate the surgical outcomes objectively, two plastic surgeons compared photographs using a 5-point Global Aesthetic Improvement Scale (GAIS) at 1, 3, 6, 12, 18, and 24 months of follow-up. Based on the GAIS objective assessment, in most patients (85%) experienced better than 3 score ("improved") changes. Approximately 42.5% of the patients experienced better than 4 score ("much improved") changes. The mean GAIS grade improved significantly (p < 0.005) without decline throughout a period of 12 months. No serious adverse complication was observed except one patient, who experienced skin irregularities and dimpling for up to 9 months after the procedure. This 4 M thread lifting is the multiple layer lifting and rejuvenation using different materials in addition to the multiple targets. Using the concepts of structural rejuvenation, the 4 M thread lifting technique presented modest to significant improvement, maintaining good results at 12 months after procedure. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy.
Isocitrate dehydrogenase 1 and 2 (IDH1/2) are enzymes recurrently mutated in various types of cancer, including glioma, cholangiocarcinoma, chondrosarcoma, and acute myeloid leukemia. Mutant IDH1/2 induce a block in differentiation and thereby contribute to the stemness and oncogenesis of their cells of origin. Recently, small-molecule inhibitors of mutant IDH1/2 have been Food and Drug Administration-approved for the treatment of IDH1/2-mutated acute myeloid leukemia. These inhibitors decrease the stemness of the targeted IDH1/2-mutated cancer cells and induce their differentiation to more mature cells. In this review, we elucidate the mechanisms by which mutant IDH1/2 induce a block in differentiation and the biological and clinical effects of the release into differentiation by mutant-IDH1/2 inhibitors. (J Histochem Cytochem 70:83-97, 2022).


Role of aflatoxin toxicity on transmissibility and pathogenicity of H9N2 avian influenza virus in turkeys.
The study was conducted to investigate the role of aflatoxin on the infectivity and transmissibility of H9N2 AI virus. The experiment was performed on 80 non-vaccinated turkeys, divided into 4 groups of 20 birds each. Group A was kept as non-infected and a non-treated negative control; Group B was inoculated intratracheally with H9N2 AI virus (1 × 10(7) EID50) at 4 weeks of age; Group C was fed on a diet containing 0.5 ppm aflatoxin from Day 1 through the entire experiment period and Group D was fed on diet containing 0.5 ppm aflatoxin as for Group C but inoculated intratracheally with H9N2 AI virus (1 × 10(7) EID50) at the fourth week of age and then mixed with naïve birds. Infected and contact birds showed clinical signs of different severity, showing the most prominent disease signs in birds of the aflatoxin + H9N2 group. All infected birds showed virus shedding, however, the pattern of virus shedding was different for birds of the aflatoxin + H9N2 group showing pronounced virus secretion. Similarly, efficient transmission of virus was observed between infected and contact birds, but more prominent virus transmission was seen in those birds inoculated and fed aflatoxin-treated diet. Moreover, significantly lower antibody titres against H9N2 AIV were observed in birds fed aflatoxin-treated diet, indicating an immunotoxic nature of aflatoxin as the reason for poor seroconversion. Similarly, decreased IFNγ mRNA expression and higher mortality (35%) suggest an immunotoxic and immunosuppressive effect of aflatoxin leading to enhanced pathogenesis of H9N2 viruses in aflatoxin-fed birds. The immunosuppressive nature of aflatoxin might delay influenza virus clearance and this may be one of the reasons for increased pathogenicity of H9N2 LPAI viruses in turkeys under field conditions.


The effect of numeric information about the likelihood of receiving a false negative or false positive result on people's attitudes towards colorectal cancer screening using faecal immunochemical testing (FIT).
To examine the impact of numeric risk information about false negative (FN) and false positive (FP) rates in fecal immunochemical testing (FIT) on attitudes towards screening. 102 people aged 45-55, living in the UK, read 6 hypothetical vignettes presented online about the use of FIT kits to detect colorectal cancer, in which information about FN and FP rates was systematically varied. Numeric FN risk information reduced people's interest in screening, perception of screening effectiveness and lowered trust in screening compared to verbal FN information. Verbal FN information reduced perceptions of screening effectiveness and trust compared to no FN information. People with high subjective numeracy reported lower trust in screening following the provision of numeric FN information but numeracy did not moderate any other associations. FP information did not affect attitudes towards FIT testing. Numeric FN risk information decreased people's perceptions of screening effectiveness and trust in the results of screening. While it influenced people's interest in screening, the effect was small. Numeric FN information has a small effect on interest in screening and could promote informed decision making without affecting screening uptake.


Improvement of phenolic compound bioaccessibility from yerba mate (Ilex paraguariensis) extracts after biosorption on Saccharomyces cerevisiae.
Great efforts have been made to increase the bioaccessibility of bioactive compounds from plant sources. This can be achieved by the innovative and effective method of biosorption of these compounds in Saccharomyces cerevisiae obtained from the industrial fermentative process (waste yeast). In this context, this research evaluated if chemical modifications of depleted yeast can improve the capacity to biosorb the phenolic compounds and if through in vitro digestion tests, this approach can increase bioaccessibility of the secondary metabolites from yerba mate. The results showed that the chemical modification of the yeast promoted an increase in the biosorption efficiency of the bioactive compounds. Mass spectrometry peaks for the phenolic compounds reduced after biosorption as observed for the caffeic and dicaffeoylquinic acids and for kaempferol and rutin. In addition, a 10% reduction of caffeine was verified after biosorption, quantified by mass spectrometry chromatography. This showing that the compounds were retained in the cells, which was also observed by an increase of cell turgidity with scanning electron microscopy (SEM). Mid-infrared spectroscopy showed that the major bands related to the components of the compounds increased proportionally after biosorption. Furthermore, an increase of bioaccessibility of the yerba mate bioactive compounds adsorbed in S. cerevisiae was verified when compared with the crude extract.


Blastocystis sp.-An emerging cause of diarrhea post stem cell transplantation.
Protozoans are endemic in the Middle East and diarrhea workup post stem cell transplant should always include stool examination for ova and parasites. We present a case of Blastocystis sp. infection in a multiple myeloma patient who developed diarrhea on day five of post-autologous stem cell transplantation. Diarrhea is a major complication and a potential cause of mortality in this population. Testing for endemic protozoan is recommended.


Effect of inoculum pretreatment on the microbial and metabolic dynamics of food waste dark fermentation.
This study systematically evaluated and compared different inoculum pretreatment methods to quickly select dark fermentative bacteria from anaerobic sludge for the bioconversion of food waste. The hydrogen (H2) production rate was found to be highest for 'heat + CO2' treated inoculum at 140.75 ± 2.61 mL/L/h compared to control experiments (60.27 ± 2.61 mL/L/h). At the same time, H2 yield was found to be highest for alkali-treated inoculum at 157.25 ± 7.62 mL/g of volatile solids (VS) added compared to control experiments (91.61 ± 1.93 mL/g VS). Analysis of organic acids suggests a Clostridial-type fermentation with acetate (0.52 to 1.60 g/L) and butyrate (1.69 to 2.42 g/L) being the major by-products. The microbial data analysis showed that Firmicutes (63.64-90.39%), Bacteroidota (1.16-21.88%), and Proteobacteria (2.09-9.93%) were dominant at the phylum level, whereas genus-level classification showed Clostridium sensu stricto 1 (6.37-42.63%), Streptococcus (1.87-28.96%), Prevotella (0.57-16.59%), and Enterococcus (0.56-14.51%) dominated under different experimental conditions.


Determinants of BMI in patients with COPD.
COPD is characterized by significant chronic inflammation that is evident not only in the pulmonary compartment but also in the circulation. Peripheral blood features of COPD include markers of oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. The presence of a systemic inflammatory response may influence quality of life by giving rise to weight loss, muscle wasting and tissue depletion. The aim of the present study was to evaluate the determinants of body mass and the value of serum tumour necrosis factor alpha (TNF-alpha) as a marker of weight loss in COPD patients, and to correlate this with the burden of oxidative stress as measured by serum malonyldialdehyde (MDA) levels. Fifty-two male COPD patients (mean age 62.55 +/- 6.81 years) were studied. After anthropometric measurements and standard spirometry, serum TNF-alpha concentration was measured by enzyme-linked immunosorbent assay using an hTNF-alpha kit, and MDA was studied spectrophotometrically using the Yoshioka-Kawada method. The mean BMI was 24.82 +/- 3.46. BMI was lower than normal (< 19) in six patients. Mean serum TNF-alpha concentration was 14.99 +/- 8.98 pg/mL and MDA was 0.93 +/- 0.13 nmol/L. There was no significant correlation between serum MDA and TNF concentrations (P = 0.140). Serum TNF-alpha and MDA concentrations were not correlated with severity of airflow obstruction or degree of hypoxaemia (P > 0.05 for all). BMI was negatively correlated with burden of smoking (pack-years) (r = -0.392, P= 0.004); but not with pulmonary function, degree of hypoxaemia, serum TNF-alpha or MDA levels. BMI was significantly lower in current smokers than ex-smokers (P = 0.041); however, serum MDA and TNF levels were similar in both groups. The results of this study indicate that body mass is related to smoking status (both pack-years and continuance of smoking) in COPD; however, serum TNF-alpha concentration does not seem to be a good marker of weight loss in these patients.


Emergency Department/Urgent Care as Usual Source of Care and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort Study.
Having a usual source of care increases use of preventive services and is associated with improved survival in the general population. We evaluated this association in adults with chronic kidney disease (CKD). Prospective, observational cohort study. Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Usual source of care was self-reported as: 1) clinic, 2) emergency department (ED)/urgent care, 3) other. Primary outcomes included incident end-stage kidney disease (ESKD), atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, hospitalization events, and all-cause death. Multivariable regression analyses to evaluate the association between usual source of care (ED/urgent care vs clinic) and primary outcomes. Among 3,140 participants, mean age was 65 years, 44% female, 45% non-Hispanic White, 43% non-Hispanic Black, and 9% Hispanic, mean estimated glomerular filtration rate 50 mL/min/1.73 m2. Approximately 90% identified clinic as usual source of care, 9% ED/urgent care, and 1% other. ED/urgent care reflected a more vulnerable population given lower baseline socioeconomic status, higher comorbid condition burden, and poorer blood pressure and glycemic control. Over a median follow-up time of 3.6 years, there were 181 incident end-stage kidney disease events, 264 atherosclerotic events, 263 incident heart failure events, 288 deaths, and 7,957 hospitalizations. Compared to clinic as usual source of care, ED/urgent care was associated with higher risk for all-cause death (HR, 1.53; 95% CI, 1.05-2.23) and hospitalizations (RR, 1.41; 95% CI, 1.32-1.51). Cannot be generalized to all patients with CKD. Causal relationships cannot be established. In this large, diverse cohort of adults with moderate-to-severe CKD, those identifying ED/urgent care as usual source of care were at increased risk for death and hospitalizations. These findings highlight the need to develop strategies to improve health care access for this high-risk population.


Clinical and bacteriological evaluation of the efficacy of piperacillin in children with pneumonia.
We aimed to prospectively evaluate the clinical and bacteriological effects of piperacillin in children with pneumonia. Twenty-eight patients (6 months to 5 years of age) with pneumonia were treated with piperacillin. In the same period, 95 strains of Haemophilus influenzae and 41 strains of Streptococcus pneumoniae were isolated in our department and the minimum inhibitory concentration (MIC) of piperacillin was determined. The clinical efficacy of piperacillin was excellent in 4 cases, good in 23, and fair in 1; the response rate was 96.4% (27/28). Among the isolates from our department, there were 4 strains (9.8%) of penicillin-susceptible S. pneumoniae (PSSP), 32 strains (78.0%) of penicillin-intermediate-resistant S. pneumoniae (PISP), and 5 strains (12.2%) of penicillin-resistant S. pneumoniae (PRSP). Against S. pneumoniae, the MIC50 and MIC90 for piperacillin were 0.5 microg/ml and 2 microg/ml, respectively. Panipenem showed the best results, followed by piperacillin, ampicillin, and flomoxef. Among the isolates from our department, there were 51 strains (53.7%) of beta-lactamase-negative ampicillin-susceptible H. influenzae, 42 strains (44.2%) of beta-lactamase-negative ampicillin-resistant H. influenzae, 1 strain (1.1%) of beta-lactamase-positive ampicillin-resistant H. influenzae, and 1 strain (1.1%) of beta-lactamase-positive amoxicillin-clavulanic acid-resistant H. influenzae. The MIC50 and MIC90 for piperacillin against H. influenzae were 0.0625 microg/ml and 0.125 microg/ml, respectively. Tazobactam/piperacillin and piperacillin showed the best results, followed by panipenem, ampicillin, and flomoxef. Piperacillin proved to be very useful for the treatment of pneumonia in children.


Characterisation of cyclic adenosine 3':5'-monophosphate phospodiesterase from Walker carcinoma sensitive and resistant to bifunctional alkylating agents.
Walker carcinoma cell lines sensitive or resistant to bifunctional alkylating agents have been found to contain multiple forms of cyclic AMP phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 220.127.116.11). These activities have been resolved using Sepharose 6B gel filtration and their apparent molecular weights have been estimated. The enzyme appears to occur in four active forms of apparent mol. wts of greater than 1 000 000, 430 000, 350 000 and 225 000, when assayed at low substrate concentrations. Evidence has been obtained which suggests that all four forms of the enzyme are composed of subunits of mol. wt of approximately 15 000 and are interconvertible. While the ionic strength of the buffer affected the predominance of the different forms, the presence of cyclic AMP at 10(-6) M had no effect on aggregation or dissociation of the enzyme. An activity shift from high molecular weight forms of the enzyme to low molecular weight forms has been found in the resistant tumour at low substrate concentration. No change in elution profile between sensitive and resistant tumours was observed for the low affinity form of the enzyme. The pH optima of the enzymes with both high and low affinity for the substrate was found to be pH 8.0 in the sensitive line. In the resistant tumour the pH optima of the high affinity form is shifted to pH 8.4 while the low affinity form remains at pH 8.0. The high affinity forms of the phosphodiesterase in the sensitive and resistant tumour also differed in their inhibition by theophylline. In both cases inhibition was of the competitive type with Ki values for the sensitive and resistant lines being 2.35 and 0.32 mM, respectively. There was no significant difference in the inhibition of the low affinity form between the sensitive and resistant tumour.


MicroRNAs Regulating Signaling Pathways: Potential Biomarkers in Systemic Sclerosis.
Systemic sclerosis (SSc) is a multisystem fibrotic and autoimmune disease. Both genetic and epigenetic elements mediate SSc pathophysiology. This review summarizes the role of one epigenetic element, known as microRNAs (miRNAs), involved in different signaling pathways of SSc pathogenesis. The expression of key components in transforming growth factor-β (TGF-β) signaling pathway has been found to be regulated by miRNAs both upstream and downstream of TGF-β. We are specifically interested in the pathway components upstream of TGF-β, while miRNAs in other signaling pathways have not been extensively studied. The emerging role of miRNAs in vasculopathy of SSc suggests a promising new direction for future investigation. Elucidation of the regulatory role of miRNAs in the expression of signaling factors may facilitate the discovery of novel biomarkers in SSc and improve the understanding and treatment of this disease.


Prevalence and burden of headache in children and adolescents in Austria - a nationwide study in a representative sample of pupils aged 10-18 years.
Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of "undifferentiated headache" (UdH) defined as mild headache lasting less than 1 hour. Within the context of a broader national mental health survey, children and adolescents aged 10-18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence [urban or rural] and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire. Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%; p < 0.001). UdH, migraine, TTH and H15+ were reported by 26.1%, 24.2%, 21.6% and 3.0% of participants. Attributable burden was high, with 42% of those with headache experiencing restrictions in daily activities. Medication use (50% overall) was highest in H15+ (67%) and still considerable in UdH (29%). HrQoL was reduced for all headache types except UdH. Participants in single parent or patchwork families had a higher probability of migraine (respectively, OR 1.5, p < 0.001; OR 1.5, p < 0.01). Participants with a migration background had a lower probability of TTH (OR 0.7, p < 0.01). Headache disorders are both very common and highly burdensome in children and adolescents in Austria. This study contributes to the global atlas of headache disorders in these age groups, and corroborates and adds knowledge of the new yet common and important diagnostic category of UdH. The findings call for action in national and international health policies, and for further epidemiological research.


Development of and Progression of Overt Heart Failure in Nonobstructive Hypertrophic Cardiomyopathy.
Only few studies aimed at identifying predictors of heart failure (HF) in hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic analyses are lacking in these patients and little is known about the natural progression of left ventricular (LV) abnormalities and their association with HF development. Aim of this study was to assess the prognostic value of LV global longitudinal strain (GLS) and other clinical and echocardiographic characteristics for the development of HF in patients with nonobstructive HC; furthermore, changes in echocardiographic parameters over time were correlated with HF development. Echocardiography was performed in 236 HC patients (68% men, age: 50 ± 14 years) at their initial visit and during follow-up (6.5(4.1 to 9.8) years). The end point of new HF development or progression to New York Heart Association class III/IV was noted and echocardiographic changes over time were compared among patients with and without HF using linear mixed model analysis. In total, 40 patients reached the HF end point. Multivariable cox regression analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22), p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were independently associated with the HF end point. Echocardiographic parameters, including GLS and LAVI, remained stable over time in patients without HF end point, but changed significantly in patients who developed HF (group-time interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV dysfunction is a progressive phenomenon in nonobstructive HC patients which can be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline as well as their changes over time are associated with HF.


PROPELLER EPI: an MRI technique suitable for diffusion tensor imaging at high field strength with reduced geometric distortions.
A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice.


Case reports: lisinopril-induced erythroderma in an 85-year-old male.
An 85-year-old male presented with a case of erythroderma secondary to lisinopril ingestion without a previous history of skin disease. While ACE inhibitors have been shown to elicit psoriatic erythroderma in previous cases, to our knowledge this is the first case report of iatrogenic erythroderma secondary to lisinopril in a patient without dermatologic comorbidities.


Deep Listwise Triplet Hashing for Fine-Grained Image Retrieval.
Hashing is a practical approach for the approximate nearest neighbor search. Deep hashing methods, which train deep networks to generate compact and similarity-preserving binary codes for entities (e.g. images), have received lots of attention in the information retrieval community. A representative stream of deep hashing methods is triplet-based hashing that learns hashing models from triplets of data. The existing triplet-based hashing methods only consider triplets that are in the form of (q,q+,q-) , where q and q+ are in the same class and q and q- are in different classes. However, the number of possible triplets is approximately the cube of training examples, triplets used in the existing methods are only a small fraction of all possible triplets. This motivates us to develop a new triplet-based hashing method that adopts many more triplets in training phase. We propose Deep Listwise Triplet Hashing (DLTH) that introduces more triplets into batch-based training and a novel listwise triplet loss to capture the relative similarity in new triplets. This method has a pipeline of two steps. In Step 1, we propose a novel way to generate triplets from the soft class labels obtained by knowledge distillation module, where the triplets in the form of (q,q+,q-) are a subset of the newly obtained triplets. In Step 2, we develop a novel listwise triplet loss to train the hashing network, which seeks to capture the relative similarity between images in triplets according to soft labels. We conduct comprehensive image retrieval experiments on four benchmark datasets. The experimental results show that the proposed method has superior performances over state-of-the-art baselines.


Membrane lipid composition modulates the binding specificity of a monoclonal antibody against liposomes.
A hybridoma secreting a monoclonal IgM 'anti-liposome' antibody was produced after injecting a mouse with liposomes containing dipalmitoylphosphatidylcholine, cholesterol, dicetyl phosphate, and lipid A. The antibody was selected by assaying for complement-dependent damage to liposomes lacking lipid A. The monoclonal antibody reacted best with liposomes containing the original immunizing mixture of lipids. Deletion of individual lipid constituents from liposomes diminished the ability of the liposomes to bind (adsorb) the antibody. Binding of the antibody was enhanced by including lipid A or galactosylceramide in the lipid bilayer, or by substituting egg phosphatidylcholine for dimyristoyl- (or dipalmitoyl-) phosphatidylcholine. Sphingomyelin could be substituted for dimyristoylphosphatidylcholine without altering the adsorption of antibody. Although the monoclonal anti-liposome antibody was completely inhibited by phosphocholine, it was probably not a conventional anti-phosphocholine antibody. The antibody apparently had a partial specificity for phosphate, and was inhibited by glycerophosphocholine, glycerophosphate, sodium phosphate, sodium sulfate, and inositol hexaphosphate, but not by choline or inositol.


Rac1 modulates the vitreous-induced plasticity of mesenchymal movement in retinal pigment epithelial cells.
The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected. One-way design with multiple levels and repeated measurement design. The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes. Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis. Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin. Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766. Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy.


Species difference in increased vascular permeability by synthetic leukotriene C4 and D4.
The activity of synthetic LTC4 was tested in guinea-pig ileum and was 200 times more potent than histamine in contraction of the ileum (3 x 10(-11) M- 3 x 10(-9) M). The activities of LTC4 and LTD4 in increased vascular permeability in guinea pigs, rats and rabbits were compared with those of histamine, bradykinin and prostaglandin (PG) E2. LTC4 was approximately equipotent to bradykinin on a molar basis in guinea pigs and rats and 5-100 times more potent than histamine. LTD4 was about 10 times more potent than LTC4 in guinea pigs and was equipotent to LTC4 in rats. On the contrary, in rabbits, neither LTC4 (up to 30 nmole/site) nor LTD4 (1 nmole/site) induced the dye exudation. These results show that species difference is present in activity of LTC4 and LTD4 in vascular permeability. Furthermore, in guinea pigs, the vascular permeability increased by LTC4 was not affected after pretreatment with pyrilamine (2.5 mg/kg, i.v.), and LTC4 and LTD4 did not potentiate the activity of bradykinin in vascular permeability.


Induction of Light Tolerance Using Narrowband UV-B in Solar Urticaria.
Solar urticaria is an uncommon photodermatosis. First-line treatment is with antihistamines; second-line treatment includes induction of light tolerance using UV phototherapy. We aimed to describe and evaluate the effectiveness of a desensitization protocol with narrowband UV-B in patients with solar urticaria. We performed a retrospective study of patients with solar urticaria with an action spectrum in the UV-A range, the visible light range, or both who had received therapy with narrowband UV-B for induction of light tolerance. Short courses of treatment were administered (<20 sessions, 3 per week) during spring. The initial dose was determined according to the skin type. The Skindex-29 was administered before treatment and after summer; a nonvalidated questionnaire was also administered after summer to evaluate disease activity and satisfaction with treatment. We included 8 patients with an action spectrum (4 with visible light and 4 with UVA plus visible light). Seventeen courses (1-6 per patient) were administered per year. The number of sessions per year ranged from 11 to 20. The mean dose of narrowband UV-B per course was 7.45J/cm2. No patients experienced flares or adverse effects during treatment. The response was satisfactory in 6 patients. The improvement in the overall Skindex-29 score was greater than 20% in 78.6% of cases. The improvement in the function and symptoms subscales was over 20% in 71% and 64% of cases, respectively. Induction of light tolerance with narrowband UV-B in solar urticaria is safe and effective in a high percentage of patients.


The use of intrauterine contraceptive devices, pelvic inflammatory disease, and Chlamydia trachomatis infection.
With the same epidemiologic approach taken in a recent study that suggested that oral contraceptive use may not protect against chlamydial pelvic inflammatory disease, the risks of chlamydial pelvic inflammatory disease were evaluated for intrauterine contraceptive device users. Compared with women using no method of contraception, intrauterine contraceptive device users were not found to be at any higher risk of cervical chlamydial infection. Whether this places intrauterine contraceptive device users at no increased risk of chlamydial pelvic inflammatory disease cannot be ascertained from the available data. Further research is needed before any conclusions can be made regarding the risks of chlamydial pelvic inflammatory disease to users of intrauterine contraceptive devices, oral contraceptives, and other contraceptive methods.


Mediastinal involvement by myxoid liposarcoma.
Metastatic involvement of the mediastinum by liposarcoma is uncommon, and clinical experience in its management is limited. A patient with liposarcoma of the lower extremity having a concomitant anterior mediastinal mass as the only manifestation of distant metastatic involvement is described.


Monoclonal antibodies to the HN glycoprotein of Newcastle disease virus. Biological characterization and use for strain comparisons.
We have isolated nine hybridomas secreting monoclonal antibodies directed against the HN glycoprotein of D26 strain of Newcastle disease virus (NDV) and classified them into three groups by their biological reactivities. The group I antibodies from six clones had high hemagglutination inhibition (HI) and neutralization titers, and exhibited neuraminidase inhibition (NI) activity with substrates, both bovine fetuin and N-acetyl neuraminlactose, although the levels of maximum inhibition were greater with the former substrate. The group II antibodies from two clones also had high HI activity but showed a strongly substrate-dependent NI, with efficient inhibition against fetuin and a total lack of inhibition against neuraminlactose. These antibodies had neutralization capacity but the titers were much lower than those of group I antibodies. One clone (group III) secreted antibody which exhibited HI and NI with either substrate but no detectable neutralization activity. Frequency of isolation of antigenic variants and competitive binding assays have shown that group I and group II antibodies may recognize distinct regions not overlapping each other whereas antibodies placed within each of the two groups are to the respective same overlapping regions. The site of group III seemed to be close to or overlap the group I determinant but distinct from group II region. Using the isolated monoclonal antibodies we compared seven heterologous strains by HI and neutralization tests as well as by enzyme-linked immunosorbent assay. The results indicated that the regions recognized by group I antibodies would be conserved among the strains whereas those by the other two antibody groups might undergo considerable changes.


Attitude of cancer patients toward diagnosis disclosure and their preference for clinical decision-making: a national survey.
There is still contradictory evidence on disclosure preferences regarding cancer diagnosis. The aim of this study was to evaluate the preference of cancer patients for knowing the truth about their disease, as well as the factors that might have an impact on these preferences. This study was conducted in 11 cancer centers in Iran. A questionnaire was used to collect data, and all patients above 15 years of age who were willing to participate were included in the study. The patients were asked if they were aware of the malignant nature of their disease, and if they came to know about their disease at the time of initial diagnosis, or later. The patients were then asked about the way they looked upon their disease. In the final part of the questionnaire, the participants were asked the level of involvement they prefer to have in making treatment decisions. In total, 1226 patients were enrolled in this study, only 565 (46.7%) of whom were aware of their disease at the time of diagnosis, and 878 (72.7%) at the time of interview, while 980 (85.2%) were willing to receive information about their disease. Patients' awareness was significantly associated with age under 50 years, female gender, having breast, skin or head and neck cancer, and having medical care in Shiraz or Hamadan while it was not associated with the stage or accompanying illness. While the majority of Iranian cancer patients prefer to be aware of the nature of their disease and have an active role in treatment decision making, they do not receive this information.


Effects of low-intensity pulsed ultrasound on the differentiation of C2C12 cells.
Low-intensity pulsed ultrasound (LIPUS) is known to accelerate bone regeneration, but the precise cellular mechanism is still unclear. The purpose of this study was to determine the effect of LIPUS on the differentiation of pluripotent mesenchymal cell line C2C12. The cells were cultured in differentiation medium with or without the addition of LIPUS stimulation. The ultrasound signal consisted of 1.5 MHz at an intensity of 70 mW/cm2 for 20 min for all cultures. To verify the cell lineage after LIPUS stimulation, mRNA expression of cellular phenotype-specific markers characterizing osteoblasts (Runx2, Msx2, Dlx5, AJ18), chondroblasts (Sox9), myoblasts (MyoD), and adipocytes (C/EBP, PPARgamma) was studied using real-time polymerase chain reaction analysis. The protein expression of Runx2 and activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were performed using Western blotting. The mRNA expression of Runx2, Msx2, Dlx5, AJ18, and Sox9 was increased markedly by the LIPUS stimulation, whereas the expression of MyoD, C/EBP, and PPARgamma was drastically decreased. In the Western blot analysis, LIPUS stimulation increased Runx2 protein expression and phosphorylation of ERK1/2 and p38 MAPK. Our study demonstrated that LIPUS stimulation converts the differentiation pathway of C2C12 cells into the osteoblast and/or chondroblast lineage via activated phosphorylation of ERK1/2 and p38 MAPK.


Spatial distribution, sources identification, and health risk assessment polycyclic aromatic hydrocarbon compounds and polychlorinated biphenyl compounds in total suspended particulates (TSP) in the air of South Pars Industrial region-Iran.
South Pars Industrial Energy Zone, located in the southwest of Iran along the Persian Gulf coast, encompasses many industrial units in the vicinity of urban areas. This research study investigated the effects of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) on human health and the environment. Suspended particulate matters (SPM) in the air sampled, in summer and winter 2019, from ten stations next to industrial units and residential areas. The samples were analyzed by gas chromatography-mass spectrometry (GC-MS). Spatial distribution maps of pollutants in the region were prepared using GIS software. The highest carcinogenic risk due to PAHs and PCBs measured as ([Formula: see text]) and ([Formula: see text], respectively. According to the US Environmental Protection Agency limit ([Formula: see text]), the cancer risks from PAH compounds were significant and need further investigation. The PCB cancer risks were within acceptable ranges. The highest adsorption ratios for PAHs were obtained through skin and PCBs by ingestion. The maximum measured non-carcinogenic hazard indexes (HI) turned out to be 0.037 and 0.023 for PAH and PCB, respectively, and were reported as acceptable risks. The predominant source of PAH in industrial areas was liquid fossil combustion, and in urban areas replaced by coal-wood-sugarcane combustion. Petrochemical complexes, flares, power plants (69%), electric waste disposal sites, and commercial pigments (31%) were reported as PCB sources. Industries activities were the most effective factors in producing the highest level of carcinogenic compounds in the region, and it is necessary to include essential measures in the reform programs.


The perfect qMR machine: Measurement variance much less than biological variance.
Implementing quantitative MR (qMR) methodology can be a time-consuming task, sometimes seemingly without an end. The concept of the Perfect qMR Machine offers the possibility that the implementation is complete and that no further improvements are needed. This is achieved by making the measurement repeatability variance much less than the biological variance. Thus the proposal is: A Perfect Quantitative MR machine is one that, in making a measurement, contributes no significant extra variation to that which already exists from biological variation. A medal system (platinum, gold, silver and bronze) recognises different sources of biological variance, depending on the type of measurement being carried out (whether a serial study or a group comparison), and different kinds of measurement variance (single machine or multi-centre). A perfect machine can in principle be demonstrated for each quantitative measure (T1, ADC etc).


Response of primary rabbit kidney proximal tubule cells to estrogens.
The effects of estrogens on the growth and function of primary rabbit kidney proximal tubule (RPT) cells have been examined in hormonally defined phenol red-free medium. 17beta-estradiol was observed to stimulate growth at dosages as low as 10(-10) M. The growth stimulatory effects of 17beta-estradiol were mitigated in the presence of hydrocortisone, suggesting that these two steroid hormones acted at least in part by common mechanisms. The effects of other steroids known to interact with the estrogen receptor were examined. Alpha estradiol was found to be growth stimulatory over a concentration range of 10(-9) to 10(-8) M, albeit to a lower extent than beta estradiol. In addition, the anti-estrogen tamoxifen was also growth stimulatory (unlike the case with the human mammary tumor cell line MCF-7). The effects of several metabolic precursors of 17beta-estradiol were examined, including testosterone, which was growth stimulatory, and progesterone, which was growth inhibitory. The growth stimulatory effects of 17beta-estradiol, alpha estradiol, and tamoxifen could possibly be explained by their interaction with an estrogen receptor. Indeed, metabolic labelling and immunoprecipitation studies indicated the presence of such an estrogen receptor in the primary cultures. The rate of biosynthesis of the estrogen receptor was found to be affected by the presence of exogenously added 17beta-estradiol. 17beta-estradiol was also observed to increase the activity of two brush border enzymes, alkaline phosphatase and gamma glutamyl transpeptidase, during the growth phase of the primary cultures.


Determination of thrombopoietin-derived peptides recognized by both cellular and humoral immunities in healthy donors and patients with thrombocytopenia.
Thrombopoietin (TPO) is a cytokine that promotes megakaryocytopoiesis and thrombopoiesis and is considered a drug suitable for patients with thrombocytopenia. However, unexpected severe thrombocytopenia has developed in some healthy individuals participating in phase I clinical trials with a pegylated recombinant human megakaryocyte growth factor (PEG-rHuMGDF) that contained the first 163 amino acids of endogenous TPO, which resulted in hampering the further development of clinical trials. Autoimmune responses to PEG-rHuMGDF, which cross-reacted with endogenous TPO, were suggested to be involved in this rare but severe adverse event, although the immunogenic epitopes have not yet been determined. To better understand the molecular basis of such autoimmune reactions, we investigated the reactivity of 18 TPO-derived peptides with HLA-A2-binding motifs to plasma and T cells, both from patients with thrombocytopenia (n=24) and from healthy donors (HDs) (n=24). Four peptides, including those possessing amino acids in receptor-binding sites, were preferentially reactive to plasma from at least 20% of the patients, whereas one peptide at position 101-109 was equally reactive to those of the patients and the HDs. Each of the five peptides had the ability to induce peptide-specific cytotoxic T lymphocytes (CTLs) in both groups, albeit with less frequency among the patients. More important, each of these five peptides had the ability to induce HLA-A2-restricted and peptide-specific CTL activity reactive to cells that produce TPO. These results may provide new insights to gain a better understanding of autoimmune reactions to TPO.


Efficacy of an imidacloprid/flumethrin collar against fleas, ticks and tick-borne pathogens in dogs.
Tick-borne diseases comprise a group of maladies that are of substantial medical and veterinary significance. A range of tick-borne pathogens, including diverse species of bacteria and protozoa, can infect both dogs and humans. Hence, the control of tick infestations is pivotal to decrease or prevent tick-borne pathogen transmission. Therefore, different commercial products with insecticidal, repellent or both properties have been developed for use on dogs. Recently, a collar containing a combination of imidacloprid 10% and flumethrin 4.5% has proven effective to prevent tick and flea infestations in dogs under field conditions and the infection by some vector-borne pathogens they transmit under laboratory-controlled conditions. From March 2011 to April 2012, a field study was conducted in a private shelter in southern Italy to assess the efficacy of the imidacloprid/flumethrin collar against tick and flea infestations and to determine if this strategy would decrease tick-borne pathogen transmission in young dogs. A total of 122 animals were enrolled in the study and randomly assigned to group A (n = 64; collared) or group B (n = 58; untreated controls). Dogs were examined monthly for ticks and fleas and systematically tested for selected tick-borne pathogens. Compared to controls, the collar provided overall efficacies of 99.7% and 100% against tick and flea infestation, respectively. The overall efficacy for the prevention of tick-borne pathogens (i.e., Anaplasma platys and Babesia vogeli) was 91.6%. This study demonstrates that the imidacloprid/flumethrin collar is efficacious against flea and tick infestation as well as tick-borne pathogen transmission to dogs under field conditions.


"A Threat to All Texas Physicians:" TMA Backs Surgeon in Defamation Suit.
Miguel Gomez, MD's well-publicized legal fight isn't over yet. In its latest turn, the Texas Medical Association is still standing behind the surgeon as he fights to uphold a verdict against one of the state's largest nonprofit hospital systems for defaming him.


Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in avian myeloblasts. Mode of action of 25-hydroxycholesterol.
25-Hydroxycholesterol inhibits cholesterol biosynthesis by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Addition of 25-hydroxycholesterol to chicken myeloblasts caused a rapid inhibition of HMG-CoA reductase activity, producing approximately an 80% decrease in enzyme activity after 60 min. The mode of action of 25-hydroxycholesterol was determined by immunoprecipitating radiolabeled enzyme from 25-hydroxycholesterol-treated myeloblasts. The decline in enzyme activity due to addition of 25-hydroxycholesterol was not associated with increased levels of [32P]PO4 incorporation into the immunoprecipitated reductase polypeptide (Mr = 94,000). Hence, 25-hydroxycholesterol did not appear to regulate reductase activity by enzyme phosphorylation, as observed for other modulators of HMG-CoA reductase. However, 25-hydroxycholesterol was shown to inhibit reductase activity by causing a 350% increase in the relative rate of reductase degradation and a 72% decrease in the relative rate of reductase synthesis. These alterations in the rates of degradation and synthesis occurred rapidly (within 10-30 min after addition of 25-hydroxycholesterol) and can account completely for the 25-hydroxycholesterol-induced inhibition of enzyme activity. The rapid decline in the rate of synthesis of HMG-CoA reductase in 25-hydroxycholesterol-treated cells was not associated with concomitant changes in the levels of reductase mRNA; therefore, suggesting that 25-hydroxycholesterol must inhibit the rate of reductase synthesis by translational regulation. We also present evidence that mRNA purified from chicken myeloblasts codes for two reductase polypeptides of Mr = 94,000 and 102,000.


[Detection of serum DKK1 in multiple myeloma and myeloma bone disease].
To study the association between the level of serum DKK1 and disease course of multiple myeloma(MM)as well as myeloma bone disease. This study enrolled 145 cases of MM(including 79 newly diagnosed MM, 19 responded MM, 47 relapsed or progressive MM) whose lytic bone disease were evaluated by conventional radiography, ELISA was used to detect the concentration of serum DKK1. Serum DKK-1 elevated in newly diagnosed MM compared with normal donors[2 155(646-35 251)vs 1 487(646-2 577) ng/L, P=0.000], those responded[1 136(431- 3 582) ng/L, P=0.001]and relapsed/progressive MM[1 695(431-3 582) ng/L, P=0.037], and the level of relapsed/progressive MM was marginally higher than the responded ones. Moreover, MM patients without lytic lesions in conventional radiography had significantly lower DKK- 1 levels than those with lytic bone disease[1 910(660-26 925)vs 2 519(646-35 251) ng/L, P=0.005]. Notably serum DKK-1 correlated with the number of bone lesions[0 vs 1-3 vs >3 lesions: 1 910(660-26 925)vs 2 155(1 369-5 974)vs 2 547(646-35 251)ng/L, P=0.018]. DKK-1 serum concentration correlated with disease course of MM and myeloma bone disease, indicating that DKK-1 was an important factor for the extent of bone disease, which supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.


Selected culturable enteric bacterial populations are modified by diet acidification and the growth promotant Tylosin.
To determine the effect of diet acidification and an in-feed antibiotic growth promotant (Tylosin, Ty) on selected culturable bacterial populations in the gastrointestinal tract (GIT) of mice. Female C57Bl mice were given a standard diet supplemented with Acid Pak (AP) or Ty in the drinking water. After 21 days, lumen and adherent populations of Enterobacteriaceae, enterococci/streptococci, and lactic acid bacteria (LAB) from the ileum, caecum, colon and faeces were enumerated. General intestinal health was assessed by the frequency of haemolytic bacteria in the different intestinal compartments. Contrary to expectations, AP and Ty significantly increased haemolytic bacteria in the lumen of the caecum and colon (P<0.05). The small but significant growth-enhancing effect of Ty (P<0.05) was associated with decreases in enterococci/streptococci and surprisingly, LAB, as well as increases in coliforms. AP, which failed to improve growth rates, reduced coliforms, had limited effects on enterococci/streptococci, and specifically failed to promote the growth of LAB populations in all intestinal compartments. Ty supplementation was also associated with a significant increase in macrolide-resistant enterococci throughout the GIT. Dietary acidification is less effective than Ty in modulating the population dynamics of selected culturable populations of enteric bacteria. The mouse can provide a useful experimental model to examine the effects of new dietary supplements, formulations or regimes on changes in microbial population dynamics, including monitoring for antibiotic resistance.


Investigation on the chemiluminescence reaction of the phenylhydrazine-luminol-peroxide system.
We studied the chemiluminescence (CL) oxidation of phenyl hydrazine-luminol with various organic and inorganic peroxides. Maximum CL intensity for this system was obtained for t-butylhydroperoxide. The enhancement in CL depended strongly on pH and was greatest at pH 12.5. The solvent drastically enhanced the CL intensity. DMSO was found to increase the CL intensity many-fold as compared to acetonitrile and water. The effect of temperature on CL intensity has also been studied. The CL spectra revealed a broad peak at 425 nm, which suggests excited 3-aminophthalate ion as the luminophor. A mechanism to explain the reactions is suggested.


[Prescription to elderly patients: reducing underuse and adverse drug reactions and improving adherence].
Many elderly people take multiple medications, usually for multiple health disorders. This "polymedication" increases the risk of iatrogenic disorders, may affect adherence to treatment, and represents an economic burden for society. It is therefore essential to optimize drug prescription to the elderly. The general practitioner is most involved in treating the elderly, who tend not to consult specialists as frequently as younger adults do. Most elderly subjects with comorbidities and polymedication are excluded from clinical trials, and geriatrics is not considered a priority during medical training. Three suboptimal prescription modalities have been described in the elderly population : "overuse", "misuse", and "underuse". Adverse drug reactions are frequent in the elderly and have a major economic cost. They are behind about 10 % of hospital admissions over the age of 65, and 20 % over 80. Yet most advers drug reactions are preventable. The public health consequences of non adherence to drug therapy are poorly documented. Elderly people may have several risk factors for non adherence, and a combination of measures may be necessary to improve the situation.


[Traumatic superior orbital fissure syndrome: Update].
The traumatic superior orbital fissure syndrome is an uncommon complication of craniomaxillofacial trauma. The diagnosis is clinical and associates ophtalmoplegia (constantly at initial clinical examination), ptosis and anaesthesia of the forehead. Young men victim of road traffic accidents are most often affected. CT-scan usually shows facial and/or craniofacial fractures more or less spreading towards the superior orbital fissure. The absence of fracture seen at the X-rays does not eliminate the diagnosis. Initial management should be multidisciplinary (maxillofacial surgeons, ophthalmologists and neurosurgeons) and conducted early if possible. It combines high-dose corticosteroids and decompression surgery if necessary. Abstention may be indicated in cases of delayed diagnosis with spontaneous improvement. Symptoms improve early but follow-up should be extended over several months given the recovery time.


Circulating immune complexes in rats bearing chemically induced tumours. II. Characterization of sera from different stages of tumour growth.
Sera from rats bearing intraperitoneal implants of an aminoazo dye-induced hepatoma were fractionated by Sephadex G200 and DEAE-cellulose ion exchange column chromatography. Isolated fractions were examined for their capacity to bind [125I]C1q as a measure of immune complex levels, and for their ability to bind soluble tumour-specific antigen as well as to react with antigens expressed at the surface of viable hepatoma cells. Elevated levels of circulating immune complexes in unfractionated serum were directly detectable during early tumour development although, following serum fractionation, immune complexes were identified at both early and late stages of tumour growth. The present findings suggest that the detection of immune complexes in unfractionated samples of late tumour-bearer serum using a C1q-binding assay is masked by the increasing production of tumour-specific antibodies and by a shift from complement fixing to non-complement-fixing tumour-specific antibodies.


Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4-aminobiphenyl.
4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed.


Cerebral Thrombosis: A Neurogenetic Approach.
Cerebral venous thrombosis (CVT) is a severe multifactorial condition with various clinical manifestations that may include headache, papilledema, seizures, focal deficits, coma and death. The mortality rate of untreated CVT is up to 50%, but it drops to 10% when CVT is properly treated. Prevention of CVT is feasible through healthy lifestyle, genetic counseling, molecular genetic analysis for common thrombophilia-related mutations, and prophylactic anticoagulative medication.


A sandwich-type electrochemical immunosensor based on Au-rGO composite for CA15-3 tumor marker detection.
A sensitive detection of carbohydrate antigen 15-3 (CA15-3) levels may allow for early diagnosis and monitoring the treatment of breast cancer, but this can only be made in routine clinical practice if low-cost immunosensors are available. In this work, we developed a sandwich-type electrochemical immunosensor capable of rapid detection of CA15-3 with an ultra-low limit of detection (LOD) of 0.08 fg mL-1 within a wide linear concentration range from 0.1 fg mL-1 to 1 µg mL-1. The immunosensor had a matrix of a layer-by-layer film of Au nanoparticles and reduced graphene oxide (Au-rGO) co-electrodeposited on screen-printed carbon electrodes (SPCE). The high sensitivity was achieved by using secondary antibodies (Ab2) labeled with horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2) as signal amplifiers, and hydroquinone (HQ) was used as an electron mediator. The immunosensor was selective for CA15-3 in human serum and artificial saliva samples, robust, and stable to permit storage at 4 °C for more than 30 days. With its high performance, the immunosensor may be incorporated into future point-of-care (POC) devices to determine CA15-3 in distinct biological fluids, including in blood and saliva samples.


Skin reactions to pimecrolimus cream 1% in patients allergic to propylene glycol: a double-blind randomized study.
The low concentration of propylene glycol (PG) in pimecrolimus cream makes it unlikely that the cream will induce a PG-related irritant or allergic contact dermatitis. To assess reactions to pimecrolimus cream in patients who are allergic to PG. A pilot double-blind within-patient study in 20 patients, with patch testing followed by a repeated open application test (ROAT). Limitations were that patch tests and ROATs were performed on normal skin, which may be less likely to develop an allergic response than would areas of active dermatitis. Positive PG patch-test results were confirmed in 16 patients. Patch-test scores were compatible with allergic reactions in only two patients. However, ROAT scores were negative for these two patients. Reactions with pimecrolimus or vehicle during ROAT were identified in three patients, but an allergic reaction was uncertain because none of these patients reacted with both pimecrolimus cream and vehicle. Reactions with pimecrolimus were significantly less frequent (p<.01) and less severe (p=.02) than with PG. In patients allergic to PG, pimecrolimus cream showed a very low potential to elicit allergic skin reactions.


A comparative CT evaluation of pharyngeal airway changes in class III patients receiving bimaxillary surgery or mandibular setback surgery.
The purpose of this study was to compare the morphologic changes of the upper airway space in Class III patients who underwent mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback) by computed tomography at 2 levels: soft palate and base of tongue. The sample consisted of 47 subjects in 2 groups who had been diagnosed as having Class III skeletal deformities and had been treated by mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback). Anteroposterior, lateral, and cross-sectional area dimensions of the airway at the level of soft palate and base of tongue were measured pre- and postoperatively on computed tomography images. Anteroposterior dimensions of the airway decreased in both groups (P < .0001); however, the reduction was significantly less in cases treated with bimaxillary surgery (P < .05). In the mandibular setback surgery group, the cross-sectional area of the airway decreased significantly (P < .001). Although the cross-sectional area of the airway decreased in the bimaxillary surgery group, the reduction was not statistically significant (P > .05). This study suggests that bimaxillary surgery can prevent narrowing of the upper airway in the correction of Class III deformities in comparison with mandibular setback surgery used as the sole treatment. Computed tomography was valuable in determining the effects of surgical treatment on pharyngeal airway dimensions.


Tetrandrine, an immunosuppressive alkaloid isolated from Steohania tetrandra S. Moore, induces the generation of Treg cells through enhancing fatty acid oxidation.
Our previous studies have demonstrated that tetrandrine can induce the generation of regulatory T (Treg) cells in vitro and in vivo. But, the underlying mechanism of tetrandrine remains obscure. Naïve CD4+ T cells are isolated from the mesenteric lymph nodes of mice for the differentiation of Treg cells. Flow cytometry is used to detect the frequencies of Treg cells. Non-targeted metabolomics analysis based on UHPLC-QTOF/MS is performed to assess the intracellular metabolic profiles. ChIP-PCR analysis is conducted to detect the level of H3K27ac at Foxp3 promoter and CNS regions. Tetrandrine treatment alters the metabolic profile of Treg cells, and pathway enrichment of differential metabolites mainly involves fatty acid oxidation (FAO). Tetrandrine promotes the mRNA expression of carnitine palmitoyl transferase-1, and increases the level of acetyl coenzyme A (acetyl-CoA) and the intracellular oxygen consumption rate. Either CPT1 inhibitor (etomoxir) or siRNA markedly diminishes the promotion of tetrandrine on Treg cell differentiation. Furthermore, tetrandrine enhances the acetylation of H3K27 in the promoter and CNS1 regions of Foxp3 through the acetyl-CoA derived from FAO. In the mice with collagen-induced arthritis, tetrandrine also induces Treg cell generation through FAO pathway. In addition, tetrandrine enhances the immunosuppressive function of Treg cells both in vitro and in vivo. The findings indicate that tetrandrine promotes Treg cell differentiation by enhancing FAO-mediated Foxp3 acetylation, and the CPT1-mediated FAO can serve as the target for the discovery of novel inducers of Treg cell generation.


Therapeutic applications of microbubbles.
Microbubbles, currently used as contrast agents have potential therapeutic applications. Microbubbles, upon insonation of sufficiently intense ultrasound will cavitate. Cavitation with microbubbles can be used to dissolve blood clots or deliver drugs. Targeting ligands and drugs can be incorporated into microbubbles to make highly specific diagnostic and therapeutic agents for activation with ultrasound. In this paper I will review some of these potential applications and experimental results using such agents for thrombolysis, drug and gene delivery.


MAnorm2 for quantitatively comparing groups of ChIP-seq samples.
Eukaryotic gene transcription is regulated by a large cohort of chromatin-associated proteins, and inferring their differential binding sites between cellular contexts requires a rigorous comparison of the corresponding ChIP-seq data. We present MAnorm2, a new computational tool for quantitatively comparing groups of ChIP-seq samples. MAnorm2 uses a hierarchical strategy for normalization of ChIP-seq data and assesses within-group variability of ChIP-seq signals based on an empirical Bayes framework. In this framework, MAnorm2 allows for abundant differential ChIP-seq signals between groups of samples as well as very different global within-group variability between groups. Using a number of real ChIP-seq data sets, we observed that MAnorm2 clearly outperformed existing tools for differential ChIP-seq analysis, especially when the groups of samples being compared had distinct global within-group variability.


Patients with alcohol problems in the emergency department, part 2: intervention and referral. SAEM Substance Abuse Task Force. Society for Academic Emergency Medicine.
Early intervention and appropriate referral of patients with alcohol problems have the potential to reduce alcohol-related morbidity and mortality. Part 1 of this series introduced screening tools that can be applied in the ED to allow early detection of at-risk drinkers. This article was developed by members of the SAEM Substance Abuse Task Force and describes assessment and intervention techniques once the at-risk or dependent drinkers has been identified. Appropriate aftercare and referral of patients found to have alcohol problems are also discussed.


Expression and purification of the active soluble form of Bacillus sphaericus binary toxin for structural analysis.
The binary toxin produced from Bacillus sphaericus is highly toxic against larvae of Culex and Anopheles mosquitoes. The two major components of the binary toxin are 42-kDa BinA and 51-kDa BinB, which are produced as crystalline inclusions during sporulation. Currently, there is no detailed knowledge of the molecular mechanism of the binary toxin, mainly due to the lack of structural information. Herein, we describe an expression protocol with modified conditions allowing production of soluble, biologically active BinA and BinB for further structural analysis. The binA and binB genes from B. sphaericus 2297 strain were independently cloned and fused with a polyhistidine tag at their N-termini. Both (His)(6)-tagged BinA and (His)(6)-tagged BinB were expressed as soluble forms at low temperature. Highly pure proteins were obtained after two-step purification by Ni-NTA affinity and size exclusion chromatography. In vitro activation by trypsin digestion generated a resistant fragment, of 40kDa for BinA, and of 45kDa for BinB, and an oligomeric complex of BinA and BinB in solution was observed after proteolytic activation. Their functional and structural properties were confirmed by a biological assay and far-UV circular dichroism, respectively. The mixture of BinA and BinB, either as a protoxin or as a trypsin-activated form, exhibited high mosquito-larvicidal activity against Culex quinquefasciatus larvae with LC(50) of about 10ng/ml, while no toxicity was observed from the single binary toxin component. Results from far-UV circular dichroism of BinA and BinB suggest the presence of mainly β-structure. The expression and purification protocols reported here will be useful for the production of the active and homogeneous binary toxin to allow further detailed structural investigation.


Critical evaluation of several years' activity aimed at the diagnosis of asymptomatic diabetes in the Province of Florence. Revision of method.
The authors have based this critical evaluation on the methods at present adopted for mass screening for symptomatic diabetes in a group of 39,405 subjects, in full working activity. The results obtained from these tests confirm the social importance of this illness in the active population. However, the authors suggest that the glycosuria test be abandoned as the primary discriminating criterium and suggest that blood glucose assay in specimens drawn two hours after a standard glucose and load (50 g as proposed by WHO) and the singling out of potential diabetic individuals by reason of their family and physiological background be adopted for this purpose. The relationship between diabetes, obesity, dysmetabolism and cardiovascular alterations lead us to stress once more the importance of primary prevention, aimed at correcting the eating habits and life style of patients with a potential predisposition to the illness.


Comprehensive reutilization of iron in iron ore tailings: preparation and characterization of magnetic flocculants.
A large number of iron ore tailings (IOTs) are produced in steel industry, posing threat to the environment during its storage and disposal. To effectively reutilize Fe in IOTs, we propose a comprehensive utilization scheme: (1) most Fe in IOTs is extracted by concentrated hydrochloric acid to form FeCl3 flocculants; (2) after separation from the FeCl3 flocculants, a small amount of Fe is absorbed on the residue solids, which is further washed out to synthesize micron Fe3O4 as magnetic seeds. Results show that the as-synthetic FeCl3 flocculants meet the product standard for FeCl3 flocculants in China (GB/T 4482-2018) after a series of treatments including rotary evaporation, neutralization, and dilution and have comparable performance with commercial polyaluminum chloride (PAC) and polyaluminum ferric chloride (PAFC). Moreover, the addition of synthetic superparamagnetic Fe3O4 (as magnetic seeds) doubled the flocculation rate compared with as-synthetic FeCl3 flocculants alone. Finally, the reutilization of Fe in IOTs can create a direct economic value of ¥ 1.27/kg IOTs, and produce 745 g high-silicon residues for further reutilization, which indicates that our comprehensive utilization scheme is of great application potential.


Structure of membrane lipids and physico-biochemical properties of the plasma membrane from Thermoplasma acidophilum, adapted to growth at 37 degrees C.
Thermoplasma acidophilum, a mycoplasma-like organism, grows optimally at 56 degrees C and pH2. The low temperature extreme of growth is 37 degrees C. The plasma membrane of cells grown at 37 degrees C was isolated and characterized physicobiochemically. Membrane lipids which comprise 25% of the membrane dry weight consist mainly of two repetitively methyl-branched C40 side chains that were ether-linked to two glycerol molecules. The lipid structures were elucidated by combined gas chromatography-mass spectroscopy, direct probe mass spectroscopy and 13C NMR. 37 degrees C-grown cells contained lipids with 42% more pentane cyclization than the 56 degrees C-grown cells. In 37 degrees C-grown cells, phospholipid and serine content decreased by about 10% each, carbohydrate content increased by 5%. EPR studies demonstrated an increase in membrane lipid fluidity of 37 degrees C-grown cells with an upper transition temperature at 35 degrees C which was shifted down by 10 degrees C compared with cells grown at 56 degrees C. Membrane-bound ATPase activities also indicated similar changes upon adaptation. There is a close correlation between membrane fluidity and physiological functioning of this membrane-bound enzyme.


[Tuberculosis of the large intestine--a differential diagnosis of inflammatory and neoplastic colon tumors].
We report on a case of ileocoecal tuberculosis. The clinical, radiological, endoscopic and pathologic findings are considered. The differential diagnosis between tuberculosis, chronic inflammatory bowel diseases and carcinoma of the colon are described.


Applying Research-Based Teaching Strategies in a Biomedical Engineering Programming Course: Introduction to Computer Aided Diagnosis.
There are increasing calls for the use of research-based teaching strategies to improve engagement and learning in engineering. In this innovation paper, we detail the application of research-based teaching strategies in a computer programming focused biomedical engineering module. This four-week, one-credit undergraduate biomedical engineering (BME) programming-based image processing module consisted of a blend of lectures, active learning exercises, guided labs, and a final project. Students completed surveys and generated concept maps at three time points in the module (pre, mid, and post) to document the impact of integrating research-based teaching strategies. Students demonstrated a significant (p < 0.05) increase in conceptual knowledge, confidence with material, and belief in the usefulness of material from the beginning to end of the module. Students also had high (> 4 out of 5) perceptions of gains in knowledge and attitudes toward instructor support. Overall, the novel design utilized multiple research-based pedagogies and increased students' conceptual knowledge, self-efficacy, and perceived usefulness of material. The proposed design is an example of how multiple research-based instructional strategies can be integrated into an undergraduate biomedical engineering course. The online version contains supplementary material available at 10.1007/s43683-021-00057-w.