[One case of Cronkhite-Canada syndrome, in which the course from onset to spontaneous curing could be followed].
The case is a 62 years old male. No polyposis was found by upper gastrointestinal endoscopy or barium enema examination performed at the time of cholecystectomy in March 1994. Symptoms such as dysgeusia, diarrhea, loss of hair and atrophy of nails began to appear from May. Examination of the digestive tract performed in October revealed clustered polyposis in the stomach, duodenum, small intestine and large intestine. Pathologically, all the polyps were found to be of the juvenile type, so a diagnosis of Cronkhite-Canada syndrome (CCS) was made. Histologic patterns of rectal polyp after polypectomy showed well differentiated adenocarcinoma continuous with the juvenile type polyp. The above-mentioned symptoms improved with the clinical course. At present, 6 years after the development of the disease, no recurrence of polyposis in the stomach and large intestine has been found. Our results suggest that ectodermal changes and lesions of the digestive tract in CCS appear and disappear in a short time.


Ultradian oscillations in blood pressure and heart rate in free-running dogs.
A long-term (14-24 h) telemetry recording of mean arterial pressure (MAP) and heart rate (HR) was obtained from conscious unrestrained dogs (n = 9) maintained in a closed environment. MAP and HR records were analyzed for their harmonic content by the fast Fourier transform method. The power spectral density functions of MAP and HR clearly revealed the existence of coherent ultradian rhythms of MAP and HR with a period of 1-2 h. HR and MAP are in phase and sustained during a 24-h period. To elucidate the nature of these rhythms, two additional studies were conducted (n = 4) in which clonidine (200 micrograms/kg) was administered systemically. In series I, a 7-h control period preceded the administration of clonidine, whereas in series II the order was reversed. Control (series I) and recovery (series II) periods were compared with a 0- to 7-h postinjection period. The results show that clonidine drastically and significantly reduces the amplitude of both MAP and HR oscillations for an average period of 7 h. This response was very consistent in both series and in all four dogs. These results implicate the central nervous system as the origin of these rhythms.


Determinants of risk-taking in HIV-associated neurocognitive disorders.
Decision-making involves fronto-striatal brain areas that are particularly vulnerable to the effects of HIV infection. Some studies report impaired decision-making in people with HIV/AIDS with past or present addictions and/or accompanying HIV-associated neurocognitive disorders (HAND). The authors investigated risk-based decision-making in HIV/AIDS, separating individuals with or without accompanying HAND. A total of 288 HIV-infected persons underwent standardized neuropsychological testing. Participants were profiled based on neuropsychological and clinical assessments into 2 groups, neurocognitively normal (NN, n = 205) and HAND (n = 83). Risk-based decision-making was assessed via the Game of Dice Task (GDT). Sample characteristics were summarized by principal component analysis (PCA) prior to regression analyses predicting GDT performance. The NN group performed within the normative range of the GDT, but the HAND group was impaired in all GDT measures. Across all participants, GDT performance was predicted by a combination of psychiatric comorbidities, alcohol abuse, education/premorbid IQ, and neuropsychological performance. Further analyses revealed marijuana use as an important additional predictor of impaired GDT performance. Within the GDT-impaired HAND group only, past or present immunosuppression emerged as the most robust predictor of GDT performance. Metabolic disorders and antiretroviral toxicity were also predictors of GDT performance in the HAND group. The majority of HIV-infected individuals were unimpaired in the GDT. Some influence of psychiatric and substance use comorbidities on GDT performance emerged in the entire cohort. However, GDT deficits were restricted to individuals with HAND, related to immunosuppression, metabolic disorders and antiretroviral toxicity in this group only. (PsycINFO Database Record


[Development of a Computer-aided Diagnosis System to Distinguish between Benign and Malignant Mammary Tumors in Dynamic Magnetic Resonance Images: Automatic Detection of the Position with the Strongest Washout Effect in the Tumor].
We propose a computer-aided diagnostic (CAD) system that uses time-intensity curves to distinguish between benign and malignant mammary tumors. Many malignant tumors show a washout pattern in time-intensity curves. Therefore, we designed a program that automatically detects the position with the strongest washout effect using the technique, such as the subtraction technique, which extracts only the washout area in the tumor, and by scanning data in 2×2 pixel region of interest (ROI). Operation of this independently developed program was verified using a phantom system that simulated tumors. In three cases of malignant tumors, the washout pattern detection rate in images with manually set ROI was ≤6%, whereas the detection rate with our novel method was 100%. In one case of a benign tumor, when the same method was used, we checked that there was no washout effect and detected the persistent pattern. Thus, the distinction between benign and malignant tumors using our method was completely consistent with the pathological diagnoses made. Our novel method is therefore effective for differentiating between benign and malignant mammary tumors in dynamic magnetic resonance images.


[Expression of human TFF3 in Escherichia coli].
To construct recombinant human TFF3 prokaryotic expressing plasmid, express it in E. coli and identify the expressed protein. The cDNA for mature peptide of TFF3 was amplified by RT-PCR from RNA of human colon tissue and inserted into the MCS of the prokaryotic expressing plasmid pET32a (+). Then TFF3 was expressed as a fusion protein by IPTG induction. The recombinant protein was determined by SDS-PAGE and Western blot with a rabbit anti-TFF3 polyclonal antibody. Sequencing result indicated that the obtained TFF3 fragment was inserted into plasmid pET32a (+) successfully and the sequence was correct. The expression level of the fusion protein was highest after 6h induction with 1 mmol/L IPTG. The result of Western blot demonstrated that the relative molecular mass of recombinant protein was about 24 x 10(3) and the protein had good antigenicity and specificity. The expression plasmid pET32a-TFF3 was constructed and expressed successfully. This study will provide a substantial basis for further study of human TFF3.


Personalized sleep staging system using evolutionary algorithm and symbolic fusion.
This paper presents a novel system for automatic sleep staging based on evolutionary technique and symbolic intelligence. Proposed system mimics decision making process of clinical sleep staging using Symbolic Fusion and considers personal singularity with an adaptive thresholds setting up system using Evolutionary Algorithm. It proved to be an effective and promising system in personalizing sleep staging. This system can also be integrated with other medical systems to realize remote sleep monitoring or home-care.


The impact of invasive treatment of superficial venous insufficiency of the lower extremities on cardiac functions.
The aim of the study was to investigate the effect of invasive treatment for chronic venous insufficiency (CVI) on cardiac hemodynamics. Fifty three patients diagnosed with saphenofemoral junction or great saphenous vein insufficiency in a level above C3 according to Clinical-Etiology-Anatomy-Pathophysiology classification were included in the study. All the patients underwent 2D echocardiography before and 3 months after the invasive treatment. In postinvasive treatment echocardiographic assessment, significant decreases in right ventricular end-diastolic diameter (p = 0.006), TAPSE (p = 0.006), tricuspid E wave velocity (p = 0.004), tricuspid E/A ratio (p < 0.001), sPAB (p = 0.017), tricuspid lateral s' wave velocity (p = 0.004), and right ventricular free wall longitudinal strain rate (p = 0.011) were observed. The invasive treatment of superficial venous insufficiency of the lower extremities may lead to reduction in the increased venous return in the supine position subclinically.


Combinatorial carbohydrate chemistry.
The application of combinatorial chemistry to the synthesis of carbohydrate-based compound collections has received increased attention in recent years. New strategies for the solution-phase synthesis of oligosaccharide libraries have been reported, and the use of monosaccharides as scaffolds in the generation of combinatorial libraries has been described. Novel approaches to the assembly of carbohydrate-based antibiotics, such as aminoglycoside analogs and vancomycin derivatives, have also been disclosed.


The effect of prolonged packing on the surface hardness of posterior composites.
This study evaluated the effect of four different packing times on the Knoop Hardness Number of three composites (Surefil, Z100 and Spectrum TPH). Ten samples of each composite were prepared for each packing time and 10 readings were made on each sample to produce the KHN. Photomicrographs were made of 147 indentations to determine whether the indentations had routinely been made on porosity-free sites. Statistical analysis was made using two-way ANOVA and least square means. Generally, as the packing time increased, the KHN decreased,and although the indentations appeared to have been made in porosity-free composite, the potential effect of porosities was not discounted. Increasing the packing time for clinical composites may result in a lower KHN and increased clinical wear, which would further increase if also associated with porosities within the composite.


Molecular Evidence of Bartonella melophagi in Ticks in Border Areas of Xinjiang, China.
Bartonella are gram-negative intracellular bacteria; certain species of Bartonella can cause diseases in mammals and humans. Ticks play a major role in the transmission of Bartonella. Xinjiang is the largest province in China according to land area and has one-third of the tick species in China; the infection rate of Bartonella in ticks in the Xinjiang border areas has not been studied in detail. Therefore, this study investigated tick infections by Bartonella in Xinjiang border areas, and the purpose of the study was to fill in gaps in information regarding the genetic diversity of tick infections by Bartonella in Xinjiang. We tested 1,549 tick samples from domestic animals (sheep and cattle) for Bartonella using ribC-PCR. Positive samples from the ribC-PCR assay for Bartonella spp. were further subjected to PCR assays targeting the ITS, rpoB and gltA genes followed by phylogenetic analyses. Bartonella DNA was detected in 2.19% (34/1,549) of tick samples, and the ITS, rpoB and gltA genes of ribC gene-positive samples were amplified to identify nine samples of Bartonella melophagi. In this study, molecular analysis was used to assess the presence and genetic diversity of B. melophagi in ticks collected from sheep and cattle from Xinjiang, China. This study provides new information on the presence and identity of B. melophagi in ticks from sheep and cattle.


Improving the gas-solids contact efficiency in a fluidized bed of CO2 adsorbent fine particles.
A modified CO(2) adsorbent is obtained by dry mixing of a Ca(OH)(2) fine powder as received with a commercial silica nanopowder. Silica nanoparticles form light agglomerates of size of the order of tens of microns, which are uniformly fluidizable. These agglomerates act as dispersants of the Ca(OH)(2) fine particles, which coat the nanoparticle agglomerates likely due to contact charging. Ca(OH)(2) particles (CO(2) adsorbent) are thus provided with a vehicle for uniform fluidization. In this way, the contact efficiency between the CO(2) adsorbent and CO(2) in the fluidized bed is greatly enhanced. Experimental results show that the improvement of Ca(OH)(2) fluidizability serves to enhance the carbonation reaction in the fluidized bed.


Dissection and Explant Culture of Murine Allantois for the In Vitro Analysis of Allantoic Attachment.
The placenta is essential for the growth and development of mammalian embryos. For this reason, numerous genetic alterations and likely also environmental insults that disturb placenta development or function can cause early pregnancy loss in mice and humans. Nevertheless, simple in vitro assays to screen for potential effects on placenta formation are lacking. Here, we focus on modeling the first and critical step in placenta formation, which consists of the attachment of the allantois to the chorion. We describe a method to rapidly assess the attachment of allantoic explants on immobilized α4β1 integrin, which serves as a chorio-mimetic substrate.This in vitro approach enables a qualitative evaluation of the attachment and spreading behavior of multiple allantois explants at different consecutive time points. The protocol may be used to investigate the effect of targeted mouse mutations, drugs, or various environmental factors that have been linked to pregnancy complications or fetal loss on allantois attachment ex vivo.


Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer.
Prostatic adenocarcinomas depend on androgen for growth and survival. First line treatment of disseminated disease exploits this dependence by specifically targeting androgen receptor function. Clinical evidence has shown that androgen receptor is reactivated in recurrent tumors despite the continuance of androgen deprivation therapy. Several factors have been shown to restore androgen receptor activity under these conditions, including somatic mutation of the androgen receptor ligand-binding domain. We have shown previously that select tumor-derived mutants of the androgen receptor are receptive to activation by bisphenol A (BPA), an endocrine-disrupting compound that is leached from polycarbonate plastics and epoxy resins into the human food supply. Moreover, we have shown that BPA can promote cell cycle progression in cultured prostate cancer cells under conditions of androgen deprivation. Here, we challenged the effect of BPA on the therapeutic response in a xenograft model system of prostate cancer containing the endogenous BPA-responsive AR-T877A mutant protein. We show that after androgen deprivation, BPA enhanced both cellular proliferation rates and tumor growth. These effects were mediated, at least in part, through androgen receptor activity, as prostate-specific antigen levels rose with accelerated kinetics in BPA-exposed animals. Thus, at levels relevant to human exposure, BPA can modulate tumor cell growth and advance biochemical recurrence in tumors expressing the AR-T877A mutation.


Marathon runner with acute hyponatremia: a neurological disorder.
We report the case of an athletic 49-year-old female who has run the 2011 Marathon of Paris and was addressed to the hospital for a confusion. The investigations revealed a cerebral edema complicating a severe hyponatremia secondary to an exercise-associated hyponatremia (EAH). Using 3% hypertonic saline solution, the evolution the patient rapidly improve allowing discharge after 7 days. We then discuss the importance of EAH in long-term efforts.


Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors participate in the analgesic but not hypnotic effects of emulsified halogenated anaesthetics.
The present study was designed to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hypnosis and analgesia induced by emulsified inhalation anaesthetics. After having established the mice model of hypnosis and analgesia by intraperitoneally injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intracerebroventricularly or intrathecally injected different doses of AMPA and then observed the effects on the sleep time using hypnosis test and the tail-withdrawal latency using the tail-withdrawal test. In hypnosis test, AMPA (50, 75 and 100 ng, intracerebroventricularly) had no distinctive effects on the sleep time of the mice treated with emulsified inhalation anaesthetics (P > 0.05). In tail-withdrawal test, AMPA (0.25, 0.5 and 1.0 ng, intrathecally) significantly and dose-dependently decreased the tail-withdrawal latency (P < 0.05 or P < 0.01) in the mice treated with emulsified anaesthetics. These results suggest that AMPA receptors may participate in the analgesic but not in the hypnotic effects induced by emulsified enflurane, isoflurane or sevoflurane.


[Early discharge and postpartum home visit during the COVID-19 pandemic at the HULP (Madrid).]
The COVID-19 pandemic caused that the Health Department of the Autonomous Region of Madrid redirected the Obstetrics, Gynecology and Neonatology emergency care. On March 24th 2020, the HULP launched a program of postpartum early discharge and home visit. The objective of this work was to detect if the care strategy "Voluntary early discharge and home visit by the midwife (2nd year EIR)" applied by the HULP during the COVID-19 pandemic had any adverse effect on the woman and/or the newborn. Cross-sectional observational descriptive study using convenience sampling among women included in the early discharge-home visit program from March 24th to May 5th 2020. 222 medical records and telephone surveys to postpartum women who complied with the inclusion criteria were analyzed. The statistical analysis was performed using SAS 9.4. The average of inpatient time was 25 hours and 15 minutes. 8.6% of newborns were sent back to the HULP, and 2.2% were readmitted for hyperbilirubinemia. 2.3% of parents took their infants to the Emergency Care Unit, but only 0.46% needed readmission. 0.4% of postpartum women were readmitted. At the discharge, 84.2% of newborns exclusively breastfed. After one week of the birth, 73.4% of infants were exclusively breastfeeding, 18% were mixed breastfeeding, and 8.6% were bottle feeding. 89.6% of women believed early discharge was appropriate. Home visit was described as "very satisfactory" in 83.3% of cases, and the care provided, in 88.7% of cases. With the early discharge-home visit program, continuity of care is provided, health problems were detected and resolved and high maternal satisfaction levels were obtained.


[The effects of ketamine, propofol and nitrous oxide on visual evoked potential during fentanyl anesthesia].
To evaluate the effects of ketamine, N2O, propofol on visual evoked potential (VEP) during fentanyl anesthesia, 14 patients undergoing transphenoid pituitary dissections were studied. Visual stimulation was done by using the goggles with red light diodes through closed eyelids and responses were recorded in one channel montage, Cz against Oz. The stimulus frequency was 1.9 flashes/sec. The VEPs were recorded from skin incision until the opening of the dura. For comparison, the preanesthesia to anesthesia values were determined. The ratio for N2 (N75) latency were 100.5 +/- 13.9% in ketamine group, 104 +/- 3.5% in N2O group, 100.5 +/- 4.2% in propofol group. The ratios for P2 (P100) latency were 97.45 +/- 5.7% in ketamine group, 101.9 +/- 3.5% in N2O group, 96.8 +/- 5.5% in propofol group. For N2P2 amplitude, the ratios were 36.3% +/- 31.4% in ketamine group, 138.5 +/- 58.0% in N2O group, 80.8 +/- 42.2% in propofol group. The percentage of inadequate recordings were 2.5 +/- 4.3% in ketamine group, 19.2 +/- 2.2% in N2O group and 20.6 +/- 16.0% in propofol group. The percentage of false positive results were 0 +/- 0% in ketamine group, 9.8 +/- 19.9% in N2O group, 12.7 +/- 13.2% in propofol group. Satisfactory anesthesia was achieved in all groups except for ketamine group which required additional medications for elevated blood pressure and intracranial pressure, and postoperative nausea and vomiting. It is concluded that there was great variability of VEP during anesthesia and surgery. Amplitude rather than latency changes were observed during anesthesia combined with fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of ginkgolides on gene expression of HIF-1alpha in primary cultured neurons].
To study the effects of ginkgolides (Gin) on the expression of hypoxia inducible factor-1 (HIF-1alpha) in hypoxic/ischemic neurons. The gene expression of HIF-1alpha pretreated with or without Gin (37.5 microg/ml) was observed by RT-PCR on primary cultured cortical neurons in the condition of hypoxia and oxygen-glucose deprivation. Some basic expression of HIF-1alpha mRNA were observed in cultured cortical neurons. The expression of HIF-1alpha mRNA increased after 24 h treatment with Gin. The level of HIF-la mRNA increased also after 1 h hypoxia and further enhanced after the pretreatment with Gin. The expression of HIF-1alpha mRNA decreased with the deprivation of both oxygen and glucose, which reversed after the pretreatment of Gin. Gin could increase the expression of HIF-1alpha mRNA in hypoxic/ischemic cortical neurons.


[Therapeutic Options for "Slow go" Patients with Chronic Lymphocytic Leukemia].
Chronic lymphocytic leukemia is a disease of older patients, most of them suffering from significant comorbidities or functional limitations (so -called 'slow- go' patients). Unfortunately, clinical trials in chronic lymphocytic leukemia have until recently focused mainly on the subgroup of younger patients in good overall condition ('go- go' patients). Clinico- biological parameters, such as performance status, calculated creatinine clearance, the number and severity of comorbidities along with individual clinical assessment can help guide decisions relating to the objectives and ultimately the intensity of treatment. Two large randomized studies have recently demonstrated that the addition of monoclonal antibodies against CD20 (obinutuzumab, rituximab and ofatumumab) to chlorambucil in untreated 'slow- go' patients resulted in a significant increase in the number of complete remissions, progression-free survival and even overall survival (for obinutuzumab and rituximab) with an acceptable safety profile. Chemoimmunotherapy combining chlorambucil with anti-CD20 antibody is thus the new standard 1st line therapy in this group of patients. Treatment of relapsed/ refractory chronic lymphocytic leukemia in 'slow- go' patients is very difficult and specific data is sparse. In this indication, we have witnessed an extraordinary breakthrough by means of small oral inhibitors interfering with B -cell receptor downstream signaling pathways: ibrutinib, the Brutons tyrosine kinase inhibitor, and idelalisib, the inhibitor of phosphatidylinositol 3- kinase δ. Both drugs radically changed the approach to the treatment of relapsed/ refractory chronic lymphocytic leukemia; relatively mild toxicity also predetermines their use in elderly/ comorbid patients. Other treatment options for relapsed/ refractory chronic lymphocytic leukemia in this subgroup include alemtuzumab, ofatumumab, high-dose glucocorticoids + anti-CD20 antibodies, or bendamustine + rituximab regimen. This review summarizes current data regarding the treatment of elderly and comorbid patients with chronic lymphocytic leukemia.


Sustained antibacterial coating with graphene oxide ultrathin film combined with cationic surface-active agents in a wet environment.
Antimicrobial surfactants contained in mouthrinse have excellent efficacy, but are not retained on the tooth surface (are rinsed away) due to their low water resistance and thus do not exhibit sustained antibacterial activity. We have developed a new coating method using graphene oxide (GO) that retains the surfactant on the tooth surface even after rinsing with water, thus providing a sustained antibacterial effect. Ultra-thin films of GO and an antimicrobial agent were prepared by (1) applying GO to the substrate surface, drying, and thoroughly rinsing with water to remove excess GO to form an ultrathin film (almost a monolayer, transparent) on the substrate surface, then (2) applying antimicrobial cationic surface active agents (CSAAs) on the GO film to form a composite coating film (GO/CSAA). GO/CSAA formation was verified by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and ζ-potential and contact angle measurements. GO/CSAA was effective at inhibiting the growth of oral pathogens for up to 7 days of storage in water, and antibacterial activity was recovered by reapplication of the CSAA. Antibacterial GO/CSAA films were also formed on a tooth substrate. The results suggest that GO/CSAA coatings are effective in preventing oral infections.


Contact with Mental Health Services After Acute Care for Self-Harm Among Adults Released from Prison: A Prospective Data Linkage Study.
To determine the care pathway and rate and predictors of mental health care contact within seven days of discharge from acute care following self-harm. In a representative cohort of adults released from prisons in Queensland, Australia, we probabilistically linked person-level, statewide ambulance, emergency department, and hospital records, both prospectively and retrospectively, and community mental health service and Medicare records prospectively, to baseline survey data. We fit multivariate modified log-linked Poisson regression models to examine the association between sociodemographic, health, and criminal justice factors and mental health care contact after self-harm. Of 217 discharges from acute care following self-harm, 55% (n = 119) received mental health care within seven days of discharge. Mental health care contact was associated with substance use disorder (adjusted relative risk (ARR) = 0.48; 95% CI: 0.27-0.85), dual diagnosis (ARR = 0.58; 95% CI: 0.41-0.82), physical health-related functioning (ARR = 0.98; 95% CI: 0.97-0.99), being female (ARR = 1.39; 95% CI: 1.02-1.90), being identified as at risk of self-harm by correctional authorities (ARR = 1.50; 95% CI: 1.07-2.09), and prior engagement with state-funded mental health care (ARR = 1.55; 95% CI: 1.08-2.22). Our findings highlight the need to improve the integration of community mental health care for people who present to acute care following self-harm with a recent history of incarceration, particularly for men and those with substance use disorder or dual diagnosis.


The impact of perioperative non-steroidal anti-inflammatory drugs use on pleurodesis following thoracic surgery.
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: in patients who have had {visceral and parietal pleural symphysis}, {do NSAIDs reduce} {the efficacy of pleurodesis}? Sixteen papers were discovered in the search. Of these, 3 human studies were included in the analysis. None showed a significantly higher rate of pleurodesis failure in patients given perioperative NSAIDs. The results from the largest study met criteria for noninferiority. Within the constraints of the study, the results suggest that systemic administration of nonsteroidal anti-inflammatory medication in the perioperative period does not necessarily attenuate effective pleurodesis. However, further study is needed as there is a clear paucity of human-based studies.


Crystal growth, phase transition, and nuclear magnetic resonance of organic-inorganic hybrid perovskite NH2(CH3)2CdCl3.
Understanding the physicochemical properties of organic-inorganic hybrid materials is essential to promote their applications. In this study, a single crystal of NH2(CH3)2CdCl3 was grown, and it exhibited a monoclinic structure. Its phase transition temperatures were 460 and 470 K, and it showed sufficient thermal stability. The changes in the NMR chemical shifts of each atom in the crystal with increasing temperature were determined; the chemical shift of 1H of NH2 in the NH2(CH3)2 cation changed with temperature, which was correlated to the changes in the chemical shift of 14N in NH2. The change in 113Cd chemical shifts indicate the change of six Cl atoms around Cd in CdCl6. Therefore, the change in the coordination geometry of CdCl6 is attributed to the change in the N-H⋯Cl hydrogen bond between the NH2(CH3)2 cation and CdCl6 anion. In addition, the 13C activation energies Ea obtained from the spin-lattice relaxation time T1ρ values are smaller than those of the 1H Ea values, suggesting that is free compared to 1H in the cation. We believe that this study furthers our fundamental understanding of organic-inorganic hybrid materials to promote their practical solar cell applications.


Export of dissolved organic carbon from peatlands under elevated carbon dioxide levels.
Peatlands represent a vast store of global carbon. Observations of rapidly rising dissolved organic carbon concentrations in rivers draining peatlands have created concerns that those stores are beginning to destabilize. Three main factors have been put forward as potential causal mechanisms, but it appears that two alternatives--warming and increased river discharge--cannot offer satisfactory explanations. Here we show that the third proposed mechanism, namely shifting trends in the proportion of annual rainfall arriving in summer, is similarly unable to account for the trend. Instead we infer that a previously unrecognized mechanism--carbon dioxide mediated stimulation of primary productivity--is responsible. Under elevated carbon dioxide levels, the proportion of dissolved organic carbon derived from recently assimilated carbon dioxide was ten times higher than that of the control cases. Concentrations of dissolved organic carbon appear far more sensitive to environmental drivers that affect net primary productivity than those affecting decomposition alone.


Crevicular Porphyromonas gingivalis-specific immunoglobulin A levels in healthy and periodontitis-affected Thai cohorts.
Abstract Aim: Immunoglobulin A is a key humoral immune component involved in defense mechanisms against infections. Periodontitis, the chronic inflammatory disease causing periodontal destruction, adversely affects adults worldwide, including Thailand. As the development of periodontitis is partly mediated by immune components, levels of total and Porphyromonas gingivalis-specific immunoglobulin A in gingival crevicular fluid of Thai cohorts were studied. Gingival crevicular fluid was collected from 24 patients with severe generalized chronic periodontitis and 22 healthy controls. The amount and concentration of total and Porphyromonas gingivalis-specific immunoglobulin A in each gingival crevicular fluid sample were determined by enzyme-linked immunosorbent assay. The control group contained the highest concentrations of both types of gingival crevicular fluid-immunoglobulin A, but the lowest levels of these antibodies were found in the deep sites of the periodontitis group. Moreover, the concentrations of gingival crevicular fluid-immunoglobulin A and the degree of periodontitis severity appeared to have an inverse relationship. There was no significant difference in the amounts of gingival crevicular fluid-immunoglobulin A in the control and periodontitis groups. This study supports the hypothesis that high concentrations of specific gingival crevicular fluid-immunoglobulin A antibodies directed against Porphyromonas gingivalis, a potent periodontic microorganism, could retard periodontitis development.


Characterization of influenza virus sialic acid receptors in minor poultry species.
It is commonly accepted that avian influenza viruses (AIVs) bind to terminal α2,3 sialic acid (SA) residues whereas human influenza viruses bind to α2,6 SA residues. By a series of amino acid changes on the HA surface protein, AIVs can switch receptor specificity and recognize α2,6 SA positive cells, including human respiratory epithelial cells. Animal species, like pigs and Japanese quail, that contain both α2,3 and α2,6 SA become ideal environments for receptor switching. Here, we describe the SA patterns and distributions in 6 common minor domestic poultry species: Peking duck, Toulouse geese, Chinese ring-neck pheasant, white midget turkey, bobwhite quail, and pearl guinea fowl. Lectins specific to α2,3 and α2,6 SA (Maakia amurensis agglutinin and Sambuca nigra agglutinin, respectively) were used to detect SA by an alkaline phosphotase-based method and a fluorescent-based method. Differences in SA moieties and their ability to bind influenza viruses were visualized by fluorescent labeling of 4 different H3N2 influenza viruses known to be specific for one receptor or the other. The geese and ducks showed α2,3 SA throughout the respiratory tract and marginal α2,6 SA only in the colon. The four other avian species showed both α2,3 and α2,6 SA in the respiratory tract and the intestines. Furthermore, the turkey respiratory tract showed a positive correlation between age and α2,6 SA levels. The fact that these birds have both avian and human flu receptors, combined with their common presence in backyard farms and live bird markets worldwide, mark them as potential mixing bowl species and necessitates improved surveillance and additional research about the role of these birds in influenza host switching.


Cutaneous malignancies of the perineum.
This review discusses multiple cutaneous malignancies that can present on the perineum. Although all of these neoplasms are uncommon, a focus will be on the more common neoplasms including extramammary Paget disease, basal cell carcinoma, squamous cell carcinoma, and melanoma. Other more rare entities discussed are superficial leiomyosarcoma, giant solitary trichoepithelioma, and cutaneous endometriosis.


A Random Walk Based Cluster Ensemble Approach for Data Integration and Cancer Subtyping.
Availability of diverse types of high-throughput data increases the opportunities for researchers to develop computational methods to provide a more comprehensive view for the mechanism and therapy of cancer. One fundamental goal for oncology is to divide patients into subtypes with clinical and biological significance. Cluster ensemble fits this task exactly. It can improve the performance and robustness of clustering results by combining multiple basic clustering results. However, many existing cluster ensemble methods use a co-association matrix to summarize the co-occurrence statistics of the instance-cluster, where the relationship in the integration is only encapsulated at a rough level. Moreover, the relationship among clusters is completely ignored. Finding these missing associations could greatly expand the ability of cluster ensemble methods for cancer subtyping. In this paper, we propose the RWCE (Random Walk based Cluster Ensemble) to consider similarity among clusters. We first obtained a refined similarity between clusters by using random walk and a scaled exponential similarity kernel. Then, after being modeled as a bipartite graph, a more informative instance-cluster association matrix filled with the aforementioned cluster similarity was fed into a spectral clustering algorithm to get the final clustering result. We applied our method on six cancer types from The Cancer Genome Atlas (TCGA) and breast cancer from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Experimental results show that our method is competitive against existing methods. Further case study demonstrates that our method has the potential to find subtypes with clinical and biological significance.


Considerations for using fluorescence polarization in the screening of G protein-coupled receptors.
Fluorescence polarization must be classified as a unique detection method relative to other intensity-based methods because both bound and unbound tracer is measured. Other fluorescence techniques require either physical removal of unbound tracer or a means for distinguishing only bound tracer. The presence of unbound tracer in the detection volume has profound consequences on how assay performance is gauged. The intent here is to provide tools for accurate assay performance assessment and to discuss some of the practical considerations necessary for understanding the advantages and limitations of the technology. An emphasis is placed on applications using G protein-coupled receptors.


Subaortic stenosis caused by two discrete membranes.
A case of subaortic stenosis caused by two discrete membranes is presented. Following demonstration of the two distinct sites of obstruction by intraventricular pressure gradients and angiocardiogram, the two membranes were excised through a transaortic approach. The importance of being aware of the occurrence of this rare anomaly is stressed, and its surgical implications are discussed.


TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b.
Despite improvements in diagnosis and treatment, breast cancer is still the most common cancer type among non-smoking females. TGF-β can inhibit breast cancer development by inducing cell cycle arrest in both, cancer cells and, as part of a senescence program in normal human mammary epithelial cells (HMEC). Moreover, TGF-β also drives cell migration and invasion, in part through the small GTPases Rac1 and Rac1b. Depletion of Rac1b or Rac1 and Rac1b in MDA-MB-231 or MDA-MB-435s breast cancer cells by RNA interference enhanced or suppressed, respectively, TGF-β1-induced migration/invasion. Rac1b depletion in MDA-MB-231 cells also increased TGF-β-induced p21WAF1 expression and ERK1/2 phosphorylation. Senescent HMEC (P15/P16), when compared to their non-senescent counterparts (P11/P12), presented with dramatically increased migratory activity. These effects were paralleled by elevated expression of genes associated with TGF-β signaling and metastasis, downregulated Rac1b, and upregulated Rac1. Our data suggest that acquisition of a motile phenotype in HMEC resulted from enhanced autocrine TGF-β signaling, invasion/metastasis-associated gene expression, and a shift in the ratio of antimigratory Rac1b to promigratory Rac1. We conclude that although enhanced TGF-β signaling is considered antioncogenic in HMEC by suppressing oncogene-induced transformation, this occurs at the expense of a higher migration and invasion potential.


Genome-Wide Characterization of Heat-Shock Protein 70s from Chenopodium quinoa and Expression Analyses of Cqhsp70s in Response to Drought Stress.
Heat-shock proteins (HSPs) are ubiquitous proteins with important roles in response to biotic and abiotic stress. The 70-kDa heat-shock genes (Hsp70s) encode a group of conserved chaperone proteins that play central roles in cellular networks of molecular chaperones and folding catalysts across all the studied organisms including bacteria, plants and animals. Several Hsp70s involved in drought tolerance have been well characterized in various plants, whereas no research on Chenopodium quinoa HSPs has been completed. Here, we analyzed the genome of C. quinoa and identified sixteen Hsp70 members in quinoa genome. Phylogenetic analysis revealed the independent origination of those Hsp70 members, with eight paralogous pairs comprising the Hsp70 family in quinoa. While the gene structure and motif analysis showed high conservation of those paralogous pairs, the synteny analysis of those paralogous pairs provided evidence for expansion coming from the polyploidy event. With several subcellular localization signals detected in CqHSP70 protein paralogous pairs, some of the paralogous proteins lost the localization information, indicating the diversity of both subcellular localizations and potential functionalities of those HSP70s. Further gene expression analyses revealed by quantitative polymerase chain reaction (qPCR) analysis illustrated the significant variations of Cqhsp70s in response to drought stress. In conclusion, the sixteen Cqhsp70s undergo lineage-specific expansions and might play important and varied roles in response to drought stress.


Quantification of the production of dihydrokaempferol by flavanone 3-hydroxytransferase using capillary electrophoresis.
A sensitive method using capillary electrophoresis for the separation, detection, and quantification of dihydrokaempferol (1) is reported. Well-resolved, sharp symmetrical peaks were obtained in grapefruit leaf extracts for 1, naringenin (2), and the internal standard, naringin (3). Long columns were required to resolve 1 from 2 in crude enzyme reactions and this resulted in run times of 60 min. The limit of detection for 1 was found to be 1.44 ng/microL (4.2 pg). The method showed excellent linearity and reproducibility. The method was used to determine the activity of flavanone 3-hydroxytransferase (F3H) in leaf tissue of grapefruit by quantification of the production of dihydrokaempferol in controlled time course reactions. The sensitivity of the method makes it adaptable to assaying F3H activity in individual young seedlings and/or in small tissue samples and requires only 100 mg of tissue.


Fibrillary glomerulonephritis presenting as crescentic glomerulonephritis.
Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that commonly presents clinically with hypertension, proteinuria, microscopic hematuria, and varying degree of renal insufficiency. Histologically, FGN can present with different patterns of glomerular injury, more commonly mesangioproliferative, membranoproliferative, and membranous nephropathy. While crescent formation has been described in some kidney biopsy series of FGN, crescentic glomerulonephritis pattern of glomerular injury has been rarely described. Optimal therapy and outcomes in FGN presenting with crescentic GN is not currently known. We report an adult patient who presented with massive proteinuria and severe renal failure. The kidney biopsy revealed crescentic FGN (C-FGN). The patient remained dialysis dependent despite immunosuppressive therapy. We also briefly review FGN, and the few reported cases of C-FGN that presented as rapidly progressive or advanced renal failure in the literature.


Inter-surgeon Variability in Cystic Artery Lymph Node Excision during Laparoscopic Cholecystectomy.
Introduction Expert opinion recommends that surgeons perform a laparoscopic cholecystectomy (LC) in a standardized manner by dissecting the hepatobiliary triangle lateral to the cystic artery lymph node (LN) to minimize the rate of a major bile duct injury. Methods To determine whether surgeons performed a laparoscopic cholecystectomy in a standardized manner, the study assessed the variability in the frequency of an LN excision. All LCs that were performed at a single hospital were identified from a prospective dataset. The presence of an LN was retrospectively determined from the histology report. Results Twenty-seven surgeons were recorded to have performed 2332 laparoscopic cholecystectomies. Out of the total number of patients, 76.8% were female. The median patient age was 42.4 years. About 60.8% of the LCs were elective, while 39.2% of them were acute. Nineteen pathologists reported that in 99% of the specimens - the LN status of 1831 (78.5%) gallbladders was reported and analyzed. Overall, the LN yield per surgeon varied from 0% to 50% (mean 18.7%). Conclusion The high inter-surgeon variability in the rate of LN excision during laparoscopic cholecystectomy shows that surgeons dissect the hepatobiliary triangle differently. The LN yield may also represent a surrogate marker of surgical technique (which is easy to measure).


Cannabis Use, Lung Cancer, and Related Issues.
The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes, with millions of regular users around the world. The recreational use of cannabis is reflective of its neuropsychiatric effects, such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment. Increasing evidence supports cannabis in the management of chemotherapy-induced nausea and vomiting (CINV) and for pain management; however, studies are limited, particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products. Smoking cannabis has not been proved to be a risk factor in the development of lung cancer, but the data are limited by small studies, misclassification due to self-reporting of use, small numbers of heavy cannabis smokers, and confounding of the risk associated with known causative agents for lung cancer (such as parallel chronic tobacco use). Cannabis and its biologically effective derivatives warrant additional research, ideally, controlled trials in which the cannabidiol and the delta-9-tetrahydrocabinol strength and use are controlled and documented.


Synthesis of stable isotope labelled steroid bis(sulfate) conjugates and their behaviour in collision induced dissociation experiments.
Steroid bis(sulfate) metabolites derived from the two-fold sulfation of unconjugated precursors represent an important yet understudied portion of the steroid profile. The investigation of these compounds in fields such as medicine or anti-doping science relies on mass spectrometry (MS) as the principal tool to identify and quantify biomarkers of interest and depends in turn on access to steroid reference materials and their stable isotope labelled (SIL) derivatives. A new [18O] stable isotope label for sulfate metabolites is reported, which allows for the selective, late-stage and 'one-pot' synthesis of a variety of SIL-steroid conjugates suitable as MS probes and internal standards. The method is applied to more comprehensively study the MS behaviour of steroid bis(sulfate) compounds through collision-induced dissociation (CID) experiments.


[Fundamental study on effects of different form of mouthguards on modal shape and damping ratio of human dry mandible].
Effect of 6 types of mouthguards on the vibratory characteristics of the human dry mandible was investigated by means of modal analysis with the impact test method. In this study, 20 test points were established on the mandible and the modal shape and damping ratio of the vibration of the mandible itself and the mandible each attached with a mouthguard were analyzed by using the FFT analyzer (CF-6400) and personal computer (PC-9801FA) with a modal analyzing software (VIBRANT-PC). The results were as follows: 1. With regard to the modal shape, there was almost no difference among the mandibles and each mandible with 6 types of mouthguard. 2. With regard to the damping ratio, there was a significant difference between the mandible itself and mandible with each mouthguard. And the effect of the mandible with each mouthguard on the damping ratio was different.


Are stem cells a potential therapeutic tool in coeliac disease?
Despite the growing understanding of its pathogenesis, the treatment of coeliac disease is still based on a lifelong gluten-free diet that, although efficacious, is troublesome for affected patients, and a definitive cure is still an unmet need. In this regard, the development of new chemical- and biological-derived agents has often resulted in unsatisfactory effects when tested in vivo, probably because of their ability to target only a single pathway, whilst the immunological cascade responsible for tissue injury is complex and redundant. The advent of cellular therapies, mainly based on the use of stem cells, is an emerging area of interest since it has the advantage of a multi-target strategy. Both haematopoietic and mesenchymal stem cells have been employed in the treatment of refractory patients suffering from autoimmune diseases, with promising results. However, the lack of immunogenicity makes mesenchymal stem cells more suitable than their haematopoietic counterpart, since their transplantation may be performed in the absence of a myeloablative conditioning regimen. In addition, mesenchymal stem cells have been shown to harbour strong modulatory effects on almost all cells involved in immune response, together with a potent regenerative action. It is therefore conceivable that over the next few years their therapeutic use will increase as their biological interactions with injured tissues become clearer.


LINK-A lncRNA activates HIF1α signaling and inhibits podocyte cell apoptosis in diabetic nephropathy.
Previous studies have revealed that long intergenic non-coding RNA for kinase activation (LINK-A), a long non-coding RNA (lncRNA) promotes disease progression in triple-negative breast cancer by activating hypoxia-inducible factor 1α (HIF1α). However, the activation of HIF1α has also been demonstrated to improve diabetic nephropathy. It is therefore reasonable to expect that LINK-A may also participate in diabetic nephropathy. In the current study, the expression of LINK-A lncRNA and HIF1α was determined in renal biopsies of patients with diabetic nephropathy. LINK-A lncRNA and HIF1α expression levels were detected by reverse transcription quantitative (RT-q) PCR and ELISA in diabetic patients without complications and used as controls. Correlations between LINK-A lncRNA and HIF1α expression were analyzed using Pearson's correlation coefficient. Effects of lncRNA and HIF1α overexpression on LINK-A lncRNA expression, HIF1α expression and cell apoptosis were assessed using RT-qPCR, western blotting and a cell apoptosis assay. The results revealed that LINK-A lncRNA and HIF1α were downregulated in patients with diabetic nephropathy, as well as in diabetic patients without complications. The lowest expression of LINK-A lncRNA and HIF1α were observed in healthy controls. A positive correlation was identified between LINK-A lncRNA and HIF1α in both patients groups, but not in the control group. LINK-A lncRNA and HIF1α overexpression inhibited the apoptosis of mouse podocyte cells under a high glucose treatment. LINK-A lncRNA overexpression also promoted HIF1α expression in mouse podocyte cells, while HIF1α overexpression did not significantly affect LINK-A lncRNA expression. In conclusion, LINK-A lncRNA may activate HIF1α signaling resulting in the improvement of diabetic nephropathy treatment.


Effect of ultrasound on preheated resin composites used as ceramic luting agents.
This study investigated the effect of ultrasound application when luting ceramic using two preheated composites that show distinct responses to preheating at 69°C: Filtek Z100 and Z350XT. RelyX Veneer was the control. Feldspar disks were luted using the resin-based luting agents (RBLAs), and ultrasound was tested. Biaxial flexure strength (σbf) was calculated at z-axial positions of the luted disks (z=0; z=-t2). Microtensile bond strength (μTBS) to ceramic was tested (n=30). Data were analyzed at α=0.05. At z=0, the σbf was higher for Z350 when ultrasound was not used. When ultrasound was applied, the σbf was similar between Z350 and Z100. At z=-t2, differences across the RBLAs were observed: Z350 was superior than Z100 and control without ultrasound. Ultrasound increased σbf for Z100 at both axial positions. The preheated composites yielded higher μTBS than the control. Ultrasonication increased the mechanical performance of ceramic luted with Z100 without influencing the film thickness.


The unrecognized prevalence of chronic kidney disease in diabetes.
Diabetes mellitus and chronic kidney disease (CKD) are common and exhibit synergistic associations with premature mortality. Current diabetes guidelines in the UK recommend annual urinary albumin and serum creatinine determinations to screen for diabetic kidney disease. The aim of this study was to estimate the burden of CKD in patients with diabetes and examine the ability of serum creatinine and albuminuria to detect clinically meaningful CKD compared with estimated glomerular filtration rate (eGFR). All adults known to have diabetes in primary and secondary care in Salford, UK, alive with independent renal function on 1 January 2004 were included in this observational study (n=7596). Demographic and laboratory parameters were obtained from the Electronic Patient Record. eGFR was determined using the 4-variable modification of diet in renal disease (MDRD) formula. Clinically meaningful CKD was defined as an eGFR <60 ml/min/1.73 m(2). Creatinine and albuminuria were measured in the preceding 2 years in 82.3 and 55.2% of subjects, respectively. In patients with CKD, normoalbuminuria was present in 48.8%, and serum creatinine was normal (<or=120 micromol/l) in 54.7%. An abnormal serum creatinine (>or=120 micromol/l) had a sensitivity and specificity of 45.3 and 100%, respectively, to identify CKD. The combination of abnormal creatinine and albuminuria had an improved performance but still failed to detect a large number with CKD (sensitivity 82.4%, specificity 75.4%). Serum creatinine failed to identify CKD more often in females (OR 8.22, CI 6.56-10.29). Undiagnosed CKD is common in diabetes. Current screening strategies, based on creatinine or albuminuria, fail to identify a considerable number of subjects with CKD. Incorporating eGFR into screening for CKD would identify individuals earlier in the natural history of the disease and enable early effective treatment to delay progression of CKD.


[Conization of the uterine cervix in prevention and diagnosis of cancer (author's transl)].
The result of conization of the uterine cervix in 446 cases was reviewd regarding the diagnostic and preventive therapeutic value of the procedure with special attention to post-operative complications. Conizations for benign lesions of the cervix in 33 patients resulted in a well formed cervix with squamous epithelium covering of the ectocervix in 32 patients. There was only 1 failure. In 413 diagnostic conizations with extensive microscopic work-up the lesion was only completely removed in 62% of the cases. In spite of careful colposcopy and Schiller iodine marking the external margin of the cone biopsy material went through the atypical lesion in 51% of the cases. It is therefore necessary to extend the limits of the cone biopsy specimen in all cases as far to the periphery and upwards into the canal as feasible. The incidence of early and late complications was 10.9%. In 133 conizations with hemostasis by cauterization the complication rate was 22.6%. This rate was reduced to a complication rate of 5.2% in 261 cases with hemostasis by suture. The commonest early complication was cervical bleeding. The only late complication was stenosis of the cervical canal. After conization of the cervix 18 of 22 pregnancies were uncomplicated. The increased incidence of cervical dystocia following conization of the cervix is significant and was the indication for Caesarean Section in 6 cases. For the prevention of cancer, the indication for conization of the cervix should be diminished in favor of an increase of the indication for hysterectomy because of the high failure rate of conization to prevent cancer (37%) and because of the relatively high incidence of complications of conization.


Trema and parasponia hemoglobins reveal convergent evolution of oxygen transport in plants.
All plants contain hemoglobins that fall into distinct phylogenetic classes. The subset of plants that carry out symbiotic nitrogen fixation expresses hemoglobins that scavenge and transport oxygen to bacterial symbiotes within root nodules. These "symbiotic" oxygen transport hemoglobins are distinct in structure and function from the nonoxygen transport ("nonsymbiotic") Hbs found in all plants. Hemoglobins found in two closely related plants present a paradox concerning hemoglobin structure and function. Parasponia andersonii is a nitrogen-fixing plant that expresses a symbiotic hemoglobin (ParaHb) characteristic of oxygen transport hemoglobins in having a pentacoordinate ferrous heme iron, moderate oxygen affinity, and a relatively rapid oxygen dissociation rate constant. A close relative that does not fix nitrogen, Trema tomentosa, expresses hemoglobin (TremaHb) sharing 93% amino acid identity to ParaHb, but its phylogeny predicts a typical nonsymbiotic hemoglobin with a hexacoordinate heme iron, high oxygen affinity, and slow oxygen dissociation rate constant. Here we characterize heme coordination and oxygen binding in TremaHb and ParaHb to investigate whether or not two hemoglobins with such high sequence similarity are actually so different in functional behavior. Our results indicate that the two proteins resemble nonsymbiotic hemoglobins in the ferric oxidation state and symbiotic hemoglobins in the ferrous oxidation state. They differ from each other only in oxygen affinity and oxygen dissociation rate constants, two factors key to their different functions. These results demonstrate distinct mechanisms for convergent evolution of oxygen transport in different phylogenetic classes of plant hemoglobins.


Infarction of a vertebral pedicle causing acute spinal cord compression.
We present a case of acute spinal cord compression due to haemorrhage following recurrent infarction of the right pedicle of the second lumbar vertebra. Such a case has not previously been reported and we describe the radiological and operative findings. Magnetic resonance imaging was particularly helpful in precisely localizing the lesion and planning surgery. The most likely diagnosis remained a solitary neoplastic deposit until confirmation of recurrent infarction was made on histological examination of the operative specimen. The histological findings were also in keeping with the episodic progression of the patients symptoms.


Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence.
The neutral theory of molecular evolution predicts that the ratio of polymorphisms to fixed differences should be fairly uniform across a region of DNA sequence. Significant heterogeneity in this ratio can indicate the effects of balancing selection, selective sweeps, mildly deleterious mutations, or background selection. Comparing an observed heterogeneity statistic with simulations of the heterogeneity resulting from random phylogenetic and sampling variation provides a test of the statistical significance of the observed pattern. When simulated data sets containing heterogeneity in the polymorphism-to-divergence ratio are examined, different statistics are most powerful for detecting different patterns of heterogeneity. The number of runs is most powerful for detecting patterns containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one end of the gene has high polymorphism and the other end has low polymorphism; and a newly developed statistic, the mean sliding G statistic, is most powerful for detecting patterns containing one or two peaks of polymorphism with reduced polymorphism on either side. Nine out of 27 genes from the Drosophila melanogaster subgroup exhibit heterogeneity that is significant under at least one of these three tests, with five of the nine remaining significant after a correction for multiple comparisons, suggesting that detectable evidence for the effects of some kind of selection is fairly common.


Integrated dystrophin analysis using immunocytochemical, biochemical and genetic techniques.
Immunocytochemistry is a powerful tool for the elucidation of clinical problems, particularly when used in conjunction with complementary techniques such as immunoblotting and DNA analysis. We would like to present an experimental example which illustrates the way these three different disciplines were brought together to investigate the defective gene product in X-linked muscular dystrophy.


Co-inhibition of adenosine 2b receptor and programmed death-ligand 1 promotes the recruitment and cytotoxicity of natural killer cells in oral squamous cell carcinoma.
Adenosine promotes anti-tumor immune responses by modulating the functions of T-cells and natural killer (NK) cells in the tumor microenvironment; however, the role of adenosine receptors in the progression of oral squamous cell carcinoma (OSCC) and its effects on immune checkpoint therapy remain unclear. In this study, we obtained the tumor tissues from 80 OSCC patients admitted at the Shandong University Qilu Hospital between February 2014 and December 2016. Thereafter, we detected the expression of adenosine 2b receptor (A2BR) and programmed death-ligand 1 (PD-L1) using immunohistochemical staining and analyzed the association between their expression in different regions of the tumor tissues, such as tumor nest, border, and paracancer stroma. To determine the role of A2BR in PD-L1 expression, CAL-27 (an OSCC cell line) was treated with BAY60-6583 (an A2BR agonist), and PD-L1 expression was determined using western blot and flow cytometry. Furthermore, CAL-27 was treated with a nuclear transcription factor-kappa B (NF-κ B) inhibitor, PDTC, to determine whether A2BR regulates PD-L1 expression via the NF-κ B signaling pathway. Additionally, a transwell assay was performed to verify the effect of A2BR and PD-L1 on NK cell recruitment. The results of our study demonstrated that A2BR and PD-L1 are co-expressed in OSCC. Moreover, treatment with BAY60-6583 induced PD-L1 expression in the CAL-27 cells, which was partially reduced in cells pretreated with PDTC, suggesting that A2BR agonists induce PD-L1 expression via the induction of the NF-κ B signaling pathway. Furthermore, high A2BR expression in OSCC was associated with lower infiltration of NK cells. Additionally, our results demonstrated that treatment with MRS-1706 (an A2BR inverse agonist) and/or CD274 (a PD-L1-neutralizing antibody) promoted NK cell recruitment and cytotoxicity against OSCC cells. Altogether, our findings highlight the synergistic effect of co-inhibition of A2BR and PD-L1 in the treatment of OSCC via the modulation of NK cell recruitment and cytotoxicity.


Interlayer coherent composite Fermi liquid phase in quantum Hall bilayers.
We introduce an interlayer coherent composite Fermi liquid for nu = 1/2 + 1/2 bilayers, in which interlayer Coulomb repulsion drives exciton condensation of composite fermions. As a result, composite fermions propagate coherently between layers--even though electrons do not--and form bonding and antibonding Fermi seas. This phase is compressible with respect to symmetric currents but quantum Hall-like in the counterflow channel. Quantum oscillations of the composite Fermi seas generate a new series of incompressible states at nu = p/[2(p +/- 1)] per layer (p an integer), which is a bilayer analogue of Jain's sequence.


Porcine endothelium activated by anti-alpha-GAL antibody binding mediates increased human neutrophil adhesion under flow.
Neutrophils participate in acute vascular rejection (AVR) of organ xenografts. Induced antibodies (Abs), including anti-Galalpha1,3Gal (alpha-Gal) Abs, have been suggested to cause AVR. We investigated the adhesion of naive human neutrophils to porcine aortic endothelial cells (PAECs) stimulated with anti-alpha-Gal Abs under conditions of flow. In addition, the ability of human neutrophils to adhere to human and porcine endothelium under static and flow conditions was evaluated. In a flow-adhesion assay, a significant increase in adhesion of human neutrophils to PAECs, but not to human aortic endothelial cells (HAECs), was detected 6 hours after anti-alpha-Gal Ab-binding. After Ab stimulation, PAECs expressed CD62E and increased levels of CD106, indicating an activated endothelial cell (EC) phenotype. In a migration assay, supernatants from Ab-stimulated PAECs induced migration of human neutrophils, which was partially blocked by anti-porcine (p) interleukin (IL)-8 Abs and an antagonist to platelet-activating factor (PAF). In static and flow-adhesion assays, no difference in adhesion of human neutrophils to unstimulated or tumor necrosis factor (TNF)-alpha-stimulated HAECs and PAECs could be detected. Our data suggest that anti-alpha-Gal Abs play an important role in the initiation of AVR by mediating adhesion and recruitment of neutrophils within an organ xenograft. In contrast with previous investigations, our data argues against a differential recognition of PAECs and HAECs by human neutrophils. Thus, to prevent AVR and accomplish long-term xenograft survival, it will be important to remove anti-alpha-Gal Abs before and after pig-to-human transplantation.


[Determination of methyl ethyl ketone in urine by headspace gas chromatography].
Objective: To establish a method for determination of methyl ethyl ketone in urine by headspace gas chromatography. Methods: In the urine sample(hereinafter referred to as urine sample), methyl ethyl ketone is pretreated by headspace technology, and a certain amount of head air is injected into the gas chromatograph, separated by capillary column, detected by hydrogen flame ionization detector, and the retention time is qualitative and the peak height is high. Peak area. Results: Good linearity was in the range of 0.01 to 6.0 μg/ml with a regression equation of y=13.316x+0.8497 and γ=0.9997.The minimum detectable concentration of methyl ethyl ketone was 0.01 μg/ml. The range intra-day RSD and inter-day RSD were 2.2%-5.5% and 2.5%-6.1% respectively. Urine samples can be stored for 20 days in the refrigerator at 4 ℃. Conclusion: The method has a high advantage of sensitivity and accuracy, and also easy to operate. Therefore, it is suitable for the determination of methyl ethyl ketone in urine.


[Complete genome sequence of 84FLi, a Hantaan virus strain isolated from the liver of fetus aborted by a pregnant women with hemmorrhagic fever with renal syndrome].
To study the complete genome sequence of the Chinese Hantaan virus vaccine strain 84FLi and learn about its molecular characters. The virus strain 84FLi was isolated from the liver of a fetus aborted by pregnant women with hemorrhagic fever with renal syndrome. The cDNAs of L M and S segments were amplified fragment by fragment using RT-PCR. The purified PCR products were sequenced directly or cloned into pMD18-T vector and then sequenced. The complete genome of strain 84FLi was composed of L ( 6 533 bp) M (3 616 bp) and S (1 688 bp) coding 2151 1135 and 429 amino acids respectively. The entire sequence composition was 3830A 2050C 2510G and 3447T the GC and AT contents were 38.52% and 61.48%. Homology analysis showed that the homologies of 84 FLi S segment nucleotide sequences with strain RG9 (isolated in Guangzhou) and strain Chen4 (isolated in Anhui) were 99.6%. There were 83.7% 84.0% and 87.2% nucleotide sequences homology with the three segments of Hantaan virus foreign standard strain 76-118 while the amino acids sequences homology with those of 76-118 were 97.5% 96.0% and 97.9% respectively. The strain 84FLi is highly related to other Chinese Hantaan virus isolates and is in the same subtype with the other two Chinese isolates RG9 and Chen4.


Differential effects of antihypertensive agents on proliferation of vascular smooth muscle cells from spontaneously hypertensive rats.
We have previously shown that Ca-antagonists and alpha-blockers substantially inhibit the cellular proliferation of cultured rat vascular smooth muscle cells (VSMC). This study explored whether these inhibitory effects on cellular proliferation differ between cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR VSMC proliferated much faster than WKY VSMC in 10% FCS. Cellular proliferation, determined by both cell number count and 3H-thymidine incorporation, was significantly blunted in the presence of either nifedipine (Nif) or bunazosin (Bun). The magnitude of these inhibitory effects was more pronounced for SHR cells than WKY cells (% reduction of 3H-thymidine uptake with Nif: 62.1 +/- 7.8% for SHR vs 75.3 +/- 10.2% for WKY, n = 6, p less than 0.05, and with Bun: 70.2 +/- 7.8% for SHR vs 82.1 +/- 9.9% for WKY, n = 6, p less than 0.05). In contrast, the intracellular water volume was unaffected by these antihypertensive agents based on equilibrium distribution of 3-O-methyl-D-glucose14C. It is concluded that SHR VSMC grow much faster than WKY VSMC and that this abnormality is innate to the SHR cells. It is also concluded that both Ca-antagonists and alpha-blockers exerted a substantial inhibitory effect on cellular proliferation of the cultured VSMC of either SHR or WKY. Furthermore, the greater inhibition of proliferation in the SHR VSMC suggests that Ca mediated- and/or alpha-receptor mediated processes of cellular proliferation of SHR could differ from that of WKY and that these abnormalities may contribute to the hyperproliferative changes of VSMC in this model.


Application of a New Dynamic Model to Predict the In Vitro Intrinsic Clearance of Tolbutamide Using Rat Microsomes Encapsulated in a Fab Hydrogel.
Currently used in vitro models for estimating liver metabolism do not take into account the physiologic structure and blood circulation process of liver tissue. The Bio-PK metabolic system was established as an alternative approach to determine the in vitro intrinsic clearance of the model drug tolbutamide. The system contained a peristaltic pump, recirculating pipeline, reaction chamber, and rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogel. The metabolism of tolbutamide at initial concentrations of 100, 150, and 200 μM was measured in both the FAB hydrogel and the circular medium. The data from the FAB hydrogel and the circular medium were fitted to a mathematical model to obtain the predicted intrinsic clearance of tolbutamide after different periods of preincubation. The in vitro clearance value for tolbutamide was incorporated into Simcyp software and used to predict both the in vivo clearance value and the dynamic process of elimination. The predicted in vivo clearance of tolbutamide was 0.107, 0.087, and 0.095 L/h/kg for i.v. injection and 0.113, 0.095, and 0.107 L/h/kg for oral administration. Compared with the reported in vivo clearance of 0.09 L/h/kg (i.v.) and 0.10 L/h/kg (oral), all the predicted values differed by less than twofold. Thus, the Bio-PK metabolic system is a reliable and general in vitro model, characterized by three-dimensional structured RLM and circulation and perfusion processes for predicting the in vivo intrinsic clearance of low-extraction compounds, making the system more analogous with the rat in terms of both morphology and physiology.


Research funding for newborn health and stillbirths, 2011-20: a systematic analysis of levels and trends.
Worldwide, an estimated 4·4 million newborn deaths and stillbirths occurred in 2020, and 98% of these deaths occurred in low-income and middle-income countries (LMICs). We aimed to analyse new research grants for newborns and stillbirth awarded by major funders in 2019-20, and all research funding allocated to LMIC-based institutions in 2011-20. For this systematic analysis, we searched Dimensions, the world's largest research funding database, for grants relevant to neonatal and stillbirth research. Included grants were categorised by in-depth content analysis, with descriptive quantitative analyses by funder and recipient countries, research pipeline, topic, and year. Globally, in 2019-20, major funders awarded a mean annual total of US$577·1 million per year for newborn and stillbirth research (mean total of 550 grants per year). $166·3 million (28·8%) of $577·1 million was directed to small and vulnerable newborn research, but only $8·4 million (1·5%) was directed to stillbirth research. The majority of funding, $537·0 million (93·0%), was allocated to organisations based in high-income countries. Between 2011 and 2020, LMIC-based recipients were named on 1985 grants from all funders worth $486·7 million, of which $73·1 million (15·0%) was allocated to small and vulnerable newborn research and $12·0 million (2·5%) was allocated to stillbirth research. Most LMIC funding supported preclinical or observational studies ($236·8 million [48·7%] of $486·7 million), with implementation research receiving only $13·9 million (2·9%). Although investment in research related to neonatal health and stillbirths has increased between 2011 and 2020, there are marked disparities in distribution geographically, between major causes of mortality, and among research pipeline types. Stillbirth research received minimal funding in both high-income countries and LMICs, despite a similar number of deaths compared with neonates. Direct investment in LMIC-led research, especially for implementation research, could accelerate the slow global progress on stillbirth prevention and newborn survival. None. For the French, German and Spanish translations of the abstract see Supplementary Materials section.


[Paleopathology of the relics of Saint Albert of Louvain].
The author recounts St. Albert of Lowen's story who was slaughtered in Reims in 1192 and after buried inside the cathedral's nave. During 1612, at request of the Archduke and Archduchess of Brabant, the King of France and the Reims Archbishop conceded the translation of the relics to Brussels. However an error on the burial place was revealed more ever by the consequences of the Great War. Indeed, the architect Henri Deneux found the genuine tomb of Albert of Lowen. The Belgian people had received the mortal remains of Archbishop Odalric about who skull examination indicated also a traumatic lesion but the death circumstances are ignored. The error of the Reims Cathedral's Canons may be explained by various modifications and above the later transformation, particularly those of the rood-screen.


Kv2.1 clusters on β-cell plasma membrane act as reservoirs that replenish pools of newcomer insulin granule through their interaction with syntaxin-3.
The voltage-dependent K+ (Kv) channel Kv2.1 is a major delayed rectifier in many secretory cells, including pancreatic β cells. In addition, Kv2.1 has a direct role in exocytosis at an undefined step, involving SNARE proteins, that is independent of its ion-conducting pore function. Here, we elucidated the precise step in exocytosis. We previously reported that syntaxin-3 (Syn-3) is the key syntaxin that mediates exocytosis of newcomer secretory granules that spend minimal residence time on the plasma membrane before fusion. Using high-resolution total internal reflection fluorescence microscopy, we now show that Kv2.1 forms reservoir clusters on the β-cell plasma membrane and binds Syn-3 via its C-terminal C1b domain, which recruits newcomer insulin secretory granules into this large reservoir. Upon glucose stimulation, secretory granules were released from this reservoir to replenish the pool of newcomer secretory granules for subsequent fusion, occurring just adjacent to the plasma membrane Kv2.1 clusters. C1b deletion blocked the aforementioned Kv2.1-Syn-3-mediated events and reduced fusion of newcomer secretory granules. These insights have therapeutic implications, as Kv2.1 overexpression in type-2 diabetes rat islets restored biphasic insulin secretion.


Effect of citrinin, a mycotoxin produced by Penicillium citrinum, on laying hens and young broiler chicks.
Citrinin fed to mature laying hens at levels of 0, 50, and 250 mug/g. of diet for three weeks had no effect on body weight, feed consumption, egg production, egg weight or egg shell quality. A moderate diarrhea occurring about three days after feeding 250 mug. citrinin/g. of diet was observed. However, the diarrhea subsided once the birds were returned to a normal diet. Young broiler chicks were fed a diet containing either 0, 62.5, 125, 250, or 500 mug. citrinin/g. of diet from hatching to three weeks of age. Body weight was decreased by the 500 mug/g. level whereas all levels of citrinin resulted in enlarged kidneys and an improvement in feed conversion when compared to control values. There was also a slight dose-related increase in liver size. The 250 and 500 mug./g. levels resulted in a dose-related increase in water consumption accompanied by an acute diarrhea. Dietary citrinin had no effect on serum protein, glucose, cholesterol, uric acid, calcium, potassium and sodium concentrations or packed cell volume.


Efficient and Stable Carbon-Based Perovskite Solar Cells Enabled by Mixed CuPc:CuSCN Hole Transporting Layer for Indoor Applications.
Perovskite solar cells (PSCs) are an innovative technology with great potential to offer cost-effective and high-performance devices for converting light into electricity that can be used for both outdoor and indoor applications. In this study, a novel hole-transporting layer (HTL) was created by mixing copper phthalocyanine (CuPc) molecules into a copper(I) thiocyanate (CuSCN) film and was applied to carbon-based PSCs with cesium/formamidinium (Cs0.17FA0.83Pb(I0.83Br0.17)3) as a photoabsorber. At the optimum concentration, a high power conversion efficiency (PCE) of 15.01% was achieved under AM1.5G test conditions, and 32.1% PCE was acquired under low-light 1000 lux conditions. It was discovered that the mixed CuPc:CuSCN HTL helps reduce trap density and improve the perovskite/HTL interface as well as the HTL/carbon interface. Moreover, the PSCs based on the mixed CuPc:CuSCN HTL provided better stability over 1 year due to the hydrophobicity of CuPc material. In addition, thermal stability was tested at 85 °C and the devices achieved an average efficiency drop of approximately 50% of the initial PCE value after 1000 h. UV light stability was also examined, and the results revealed that the average efficiency drop of 40% of the initial value for 70 min of exposure was observed. The work presented here represents an important step toward the practical implementation of the PSC as it paves the way for the development of cost-effective, stable, yet high-performance PSCs for both outdoor and indoor applications.


Rapid softening of acidified peppers: effect of oxygen and sulfite.
Evidence was found for two previously unreported, nonenzymatic reactions that affected texture retention in acidified red bell peppers. First, oxygen was found to cause rapid softening of the pepper tissue such that it lost at least 40% of the initial tissue firmness within 2 weeks after acidification. Second, sulfite added to the acidified peppers prevented the softening caused by oxygen. Combined addition of sulfite and calcium chloride resulted in better retention of tissue firmness during extended storage than the addition of either component by itself.


Shock wave therapy induces neovascularization at the tendon-bone junction. A study in rabbits.
Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown. We hypothesized that shock wave therapy induces the ingrowth of neovascularization and improves blood supply to the tissues. The purpose of this study was to investigate the effect of shock wave therapy on neovascularization at the tendon-bone junction. Fifty New Zealand white rabbits with body weight ranging from 2.5 to 3.5 kg were used in this study. The right limb (the study side) received shock wave therapy to the Achilles tendon near the insertion to bone. The left limb (the control side) received no shock wave therapy. Biopsies of the tendon-bone junction were performed in 0, 1, 4, 8 and 12 weeks. The number of neo-vessels was examined microscopically with hematoxylin-eosin stain. Neovascularization was confirmed by the angiogenic markers including vessel endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expressions and endothelial cell proliferation determined by proliferating cell nuclear antigen (PCNA) expression examined microscopically with immunohistochemical stains. The results showed that shock wave therapy produced a significantly higher number of neo-vessels and angiogenesis-related markers including eNOS, VEGF and PCNA than the control without shock wave treatment. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined at 12 weeks; whereas the increases of PCNA and neo-vessels began at 4 weeks and persisted for 12 weeks. In conclusion, shock wave therapy induces the ingrowth of neovascularization associated with early release of angiogenesis-related markers at the Achilles tendon-bone junction in rabbits. The neovascularization may play a role to improve blood supply and tissue regeneration at the tendon-bone junction.


The complete chloroplast genome of Petunia exserta (Solanaceae: Petunioideae), an endangered ornamental species.
Petunia exserta is an ornamental species on the brink of extinction in the wild. We report here the complete chloroplast genome of P. exserta, which is 156,598 bp in size consisting of a large single-copy region (87,095 bp), a small single-copy region (18,643 bp), and a pair of inverted repeats (25,430 bp for each). The chloroplast (used 'cp' hereafter) genome contains 132 genes, including 8 rRNA genes, 37 tRNA genes, and 87 protein-coding genes. Phylogenetic analysis demonstrated that P. exserta was most closely related to P. hybrida, and they together were closer to Calibrachoa hybrida than other taxa in the Solanaceae family.


Catalytic asymmetric exo-selective [6+3] cycloaddition of iminoesters with fulvenes.
A novel exo-selective [6+3] cycloaddition approach for the highly enantioselective synthesis of polysubstituted piperidines was developed. The developed methodology was applied in a one-pot [6+3]-[4+2] dicycloaddition, allowing the construction of structurally and stereochemically rich polycyclic compounds from simple building blocks.


Characterization of "unhealed gastric ulcers" produced with chronic exposure of acetic acid ulcers to indomethacin in rats.
We previously discovered that a 4-wk course of indomethacin delivered to rats with acetic acid ulcers resulted in production of "unhealed gastric ulcers" that persisted for up to 12 wks after treatment cessation. The present study examined the mechanism underlying such "unhealed gastric ulcers" with biochemical and histological procedures. "Unhealed gastric ulcers" were induced with a 4-wk indomethacin treatment (1 mg/kg, twice daily) in rats with acetic acid ulcers. Two and 4 wks after treatment cessation, ulcer size was significantly larger in rats receiving indomethacin compared with control animals. Ulcerated tissue prostaglandin E2 levels were significantly lower during indomethacin treatment, but the levels tended to increase after treatment cessation compared with levels measure in the group receiving vehicle. Myeloperoxidase activity levels were significantly higher during indomethacin treatment; such levels persisted after treatment cessation. Histologically, greater degrees of fibrosis and neutrophil accumulation, as well as a lesser degree of angiogenesis were observed in the "unhealed gastric ulcers" compared to ulcers that healed in a normal fashion. It was concluded that severe fibrosis, persistent neutrophil infiltration, and poor angiogenesis in the ulcer base might represent factors involved in the mechanism underlying production of "unhealed gastric ulcers".


Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children.
Early life exposure to bisphenol A (BPA), an endocrine disrupting chemical used in some food and beverage containers, receipts, and dental sealants, has been associated with anxiety and hyperactivity in animal studies. A few human studies also show prenatal and childhood BPA exposure to be associated with behavior problems in children. We measured BPA in urine from mothers during pregnancy and children at 5 years of age (N=292). Child behavior was assessed by mother and teacher report at age 7 years and direct assessment at age 9 years. Prenatal urinary BPA concentrations were associated with increased internalizing problems in boys, including anxiety and depression, at age 7. No associations were seen with prenatal BPA concentrations and behaviors in girls. Childhood urinary BPA concentrations were associated with increased externalizing behaviors, including conduct problems, in girls at age 7 and increased internalizing behaviors and inattention and hyperactivity behaviors in boys and girls at age 7. This study adds to the existing literature showing associations of early life BPA exposure with behavior problems, including anxiety, depression, and hyperactivity in children. Additional information about timing of exposure and sex differences in effect is still needed.


Building and Sustaining Strong Public Health Agencies: Determinants of Workforce Turnover.
Workforce shortages have been identified as a priority for US public health agencies. Voluntary turnover results in loss of expertise and institutional knowledge as well as high costs to recruit and train replacement workers. To analyze patterns and predictors of voluntary turnover among public health workers. Descriptive analysis and linear probability regression models. Employees of state health agencies in the United States who participated in the Public Health Workforce Interests and Needs Survey (PH WINS). Intended retirement and voluntary departure; pay satisfaction; job satisfaction. Nearly 25% of workers reported plans to retire before 2020, and an additional 18% reported the intention to leave their current organization within 1 year. Four percent of staff are considering leaving their organization in the next year for a job at a different health department. There was significant heterogeneity by demographic, socioeconomic, and job characteristics. Areas such as administration/management, health education, health services, social services, and epidemiology may be particularly vulnerable to turnover. The strongest predictors of voluntary departure were pay and job satisfaction, which were associated with 9 (P < .001) and 24 (P < .001) percentage-point decreases, respectively, in the probability to report the intention to leave. Our findings suggest that if all workers were satisfied with their job and pay, intended departure would be 7.4%, or less than half the current 18% rate. Controlling for salary levels, higher levels of education and longer work experience were associated with lower pay satisfaction, except for physicians, who were 11 percentage points (P = .02) more likely to be satisfied with their pay than employees with doctoral degrees. Several workplace characteristics related to relationships with supervisors, workplace environment, and employee motivation/morale were significantly associated with job satisfaction. Our findings suggest that public health agencies may face significant pressure from worker retirement and voluntary departures in coming years. Although retirement can be addressed through recruitment efforts, addressing other voluntary departures will require focusing on improving pay and job satisfaction.


Impact of Mycoplasma hyopneumoniae and Lawsonia intracellularis on the performance of pigs divergently selected for feed efficiency.
Feed efficiency (FE) is a valuable trait, yet how genetic selection for enhanced FE affects other processes such as response to disease is unknown. Disease from endemic respiratory and enteric pathogens such as Mycoplasma hyopneumoniae (Mh) and Lawsonia intracellularis (LI) are common in swine production. Therefore, the aim of this study was to examine if pigs selected for high vs. low FE based on residual feed intake (RFI) respond differently to a dual respiratory and enteric challenge. Pigs selected for low RFI (LRFI, high FE) are considered more FE compared to their high RFI (HRFI, low FE) selected counterparts. Using a 2 × 2 factorial design, 25 littermate pairs from the HRFI and 25 littermate pairs from the LRFI line (barrows, 50 ± 7 kg BW) were selected, with one pig from each pair assigned to individual pens in either the challenge or the nonchallenge (control) rooms (n = 25 barrows/line/challenge). On days post inoculation (dpi) 0, the challenged pigs were inoculated with LI and Mh (MhLI). Feed intake, BW, fecal swabs, and serum samples were collected and recorded weekly for 42 d. On dpi -2 and 47, 14 littermate pairs (n = 7 barrows/line/challenge) were utilized for initial and final body composition scans using dual-energy X-ray absorptiometry to calculate longitudinal whole body tissue accretion rates for lean, protein, fat, and bone mineral content. Serum antibody levels and fecal shedding of LI were used to confirm infection. Control pigs remained negative by all measures during the 6-wk trial and MhLI inoculated pigs were confirmed positive via serological antibody responses by dpi 14 for LI and Mh. There were no interactions between RFI line and challenge status for any overall performance parameter (P > 0.05). The 6-wk MhLI challenge resulted in a 17% reduction in ADG, a 12% reduction in ADFI, and a 7% reduction in G:F vs. Controls (P < 0.05). In addition, compared to the Control pigs, MhLI challenge reduced lean, protein, and lipid accretion rates by 16% (P < 0.05). Genetic selection for high FE resulted in decreased ADFI and increased G:F (P < 0.01), but did not impact ADG or tissue accretion vs. low FE pigs. Collectively, these results demonstrate that a dual enteric and respiratory pathogen challenge reduced ADG, ADFI, G:F, and tissue accretion in growing pigs. Further, there was no evidence that selection for enhanced FE based on RFI index affects response to disease.


Increasing N content in GaNAsP nanowires suppresses the impact of polytypism on luminescence.
Cathodoluminescence (CL) and micro-photoluminescence spectroscopies are employed to investigate effects of structural defects on carrier recombination in GaNAsP nanowires (NWs) grown by molecular beam epitaxy on Si substrates. In the NWs with a low N content of 0.08%, these defects are found to promote non-radiative (NR) recombination, which causes spatial variation of the CL peak position and its intensity. Unexpectedly, these detrimental effects can be suppressed even by a small increase in the nitrogen composition from 0.08% to 0.12%. This is attributed to more efficient trapping of excited carriers/excitons to the localized states promoted by N-induced localization and also the presence of other NR channels. At room temperature, the structural defects no longer dominate in carrier recombination even in the NWs with the lower nitrogen content, likely due to increasing importance of other recombination channels. Our work underlines the need in eliminating important thermally activated NR defects, other than the structural defects, for future optoelectronic applications of these NWs.


Is inhaled nitric oxide a miraculous molecule? The analysis of nitric oxide use in newborns with persistent pulmonary hypertension of the newborn.
The aim of this study was to establish a set of hospitalised patients with persistent pulmonary hypertension of the newborn (PPHN) by using retrospective analysis according to gestational age, position during childbirth, type of childbirth, dosage and length of the treatment by inhaled nitric oxide (NO) and application of inotropic agents as well as interindividual specifics and the background of PPHN. Our cohort consisted of 11 newborns who were hospitalised in Neonatal Department of Intensive Medicine between 1st January 2017 and 31st December 2019. Four of these patients were born prematurely. Only two out of eleven patients were born vaginally. Nine of the newborns were diagnosed with secondary PPHN, in three of these cases it was caused by infection. The highest dose of inhaled nitric oxide used was 40 ppm. The focus of this paper was the therapeutic use of nitric oxide, its various applications and the effect of it on pulmonary circulation of the newborn. Inhaled NO is a selective pulmonary vasodilator used as a therapeutic agent for PPHN of the newborn. The conclusions of this paper can be beneficial in the development of better therapeutic strategies for patients with PPHN in the future (Tab. 3, Fig. 1, Ref. 40).


Exploring the Pivotal Role of the CK2 Hinge Region Sub-Pocket in Binding with Tricyclic Quinolone Analogues by Computational Analysis.
Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC50 > 500 nM) and 27h (IC50 > 1000 nM) to CK2 is abolished. However, the unbinding mechanisms due to the key pharmacophore group replacement of compounds 27e and 27h are unveiled. In the present work, combined computational analysis was performed to investigate the underlying structural basis of the low-affinity of two systems. As indicated in the results, the loss of hydrogen bonds between the non-2,6-naphtyridine and the hinge region destroyed the proper recognition of the two complexes. Besides, the allosteric mechanisms between the deviated ligands and the changed regions (G-loop, C-loop and β4/β5 loop) are proposed. Furthermore, energetic analysis was evaluated by detailed energy calculation and residue-based energy decomposition. More importantly, the summary of known polar pharmacophore groups elucidates the pivotal roles of hinge region sub-pocket in the binding of CK2 inhibitors. These results provide rational clues to the fragment-based design of more potent CK2 inhibitors.


The roles of fatalism, self-confidence, and intellectual resources in the disablement process in older adults.
In this study, the authors examined the relations between 3 psychological variables-fatalism, self-confidence, and intellectual resources-and the subsequent development of illness and disability 20 years later in an adult sample. Results indicated that greater fatalism, assessed in 1974, predicted greater difficulty in everyday cognitive tasks as well as illness in 1994. Higher self-confidence in 1974 was associated with lesser degrees of cognitive and fine motor difficulty in 1994. Greater intellectual resources in 1974 (a combination of intellectual flexibility and education) predicted less cognitive and gross motor difficulty as well as lesser degrees of illness in 1994. Some of these relations were stronger for older than for middle-aged individuals. Results are discussed in the context of models of the disablement process.


Trends and Risk Factors for Surgical Site Infection after Treatment of the Ankle Fracture: National Cohort Study.
Surgical site infection (SSI) is a major complication after the surgical treatment of ankle fractures that can result in catastrophic consequences. This study aimed to determine the incidence of SSI in several cohorts from national insurance databases over the past 12 years and identify its predictors. The claimed data for patients (n = 1,449,692) with ankle fractures between 2007 and 2019 were investigated, and a total of 41,071 patients were included in the final analysis. The covariates included were age, sex, season, fracture type (closed vs. open), type of surgical fixation procedure, and comorbidities of each patient. All subjects were divided into two groups according to the SSI after the surgical fixation of the ankle fracture (no infection group vs. infection group). The number of SSIs after the surgical treatment of ankle fractures was 874 (2.13%). Open fractures [odds ratio, (OR) = 4.220] showed the highest risk for SSI, followed by the male sex (OR = 1.841), an increasing number of comorbidities (3-5, OR = 1.484; ≥6, OR = 1.730), a history of dementia (OR = 1.720) or of myocardial infarction (OR = 1.628), and increasing age (OR = 1.010). The summer season (OR = 1.349) showed the highest risk among the four seasons for SSI after ankle fracture surgery.


Browning of perivascular adipose tissue prevents vascular dysfunction and reduces hypertension in angiotensin II-infused mice.
Hypertension is a world-leading cause of cardiovascular disease and premature deaths. Vascular tone is in part regulated by perivascular adipose tissue (PVAT) that releases pro and anticontractile factors. In hypertension, dysfunctional PVAT is observed and studies have indicated a causal relationship between dysfunctional PVAT and vascular damage in hypertension. The phenotype of PVAT on resistance vessels is primarily white adipose tissue. The present study investigates the impact of a changed phenotype, i.e., browning of PVAT, on vascular function and the development of hypertension. Browning was induced by β3-adrenergic agonist in control and angiotensin II-induced hypertensive mice. Studied parameters included blood pressure by tail-cuff plethysmography and vascular function by wire myography. Browning was confirmed through an immunohistochemical and gene analysis approach. The anticontractile effect of PVAT is lost in untreated hypertensive mice and vascular tone and blood pressure are increased. Browning of PVAT resulted in a maintained anticontractile effect, improved endothelial function, and reduced development of hypertension. Phenotype of PVAT is a major determinant of PVAT health during hypertensive conditions. Our data clearly demonstrates that browning of PVAT, i.e. changing the phenotype of PVAT, protects the vascular function and counteract the development of hypertension. This study provides novel insights into how PVAT can be protected in pathologies and thus limit the development of hypertension.


A lot of strange attractors: chaotic or not?
Iterations on R given by quasiperiodic displacement are closely linked with the quasiperiodic forcing of an oscillator. We begin by recalling how these problems are related. It enables us to predict the possibility of appearance of strange nonchaotic attractors (SNAs) for simple increasing maps of the real line with quasiperiodic displacement. Chaos is not possible in this case (Lyapounov exponents cannot be positive). Studying this model of iterations on R for larger variations, beyond critical values where it is no longer invertible, we can get chaotic motions. In this situation we can get a lot of strange attractors because we are able to smoothly adjust the value of the Lyapounov exponent. The SNAs obtained can be viewed as the result of pasting pieces of trajectories, some of which having positive local Lyapounov exponents and others having negative ones. This leads us to think that the distinction between these SNAs and chaotic attractors is rather weak.