[Sepsis in a woman with severe portosystemic encephalopathy. An uncommon complication of drug therapy].
A 60-year-old woman was referred to our hospital, because she was unarousable. She was known to have an impaired liver function due to long-lasting alkohol abuse. Third-party medical history did not explain the patient's condition. The history and laboratory findings suggested hepatic coma, therefore treatment with ornithin-aspartat, rifaximin, lactulose and antibiotics was started. Lactate concentration indicated severe hypoxic damage. The clinical examinations and circulatory parameters lead to the diagnosis of sepsis, which was suspected to be caused by spontaneous bacterial peritonitis. Computed tomography of the abomen demonstrated colitis but no other pathologic intestinal finding. Inspite of intensive therapy with antibiotics, fluids and catecholamines the patient died 3 days after admission. Autopsy revealed the cause of sepsis: a tablet, swallowed with its blister package had led to a perforation of the terminal ileum. Apart from the most cause of peritonitis in patients with liver cirrhosis - the spontaneous bacterial peritonitis - a secondary cause must also be taken into account as a reason for sepsis. A well prepared history could possibly show the direction for detection of the cause.


Colorectal cancer.
I'd like to summarize by letting you know that the field is very aggressively expanding in the areas of molecular biology. There isn't much new in terms of chemotherapy or surgery other than the advances I've just spoken to you about, but I think screening tests will allow us to decrease the mortality from colon cancer. We have been able to document that sigmoidoscopy can decrease the risk of colon cancer by about 45 percent in the United States; the mortality rates are continuing to decrease. I'd be happy to answer some questions that I might have stimulated. Thank you.


Dynamic habitat suitability modelling reveals rapid poleward distribution shift in a mobile apex predator.
Many taxa are undergoing distribution shifts in response to anthropogenic climate change. However, detecting a climate signal in mobile species is difficult due to their wide-ranging, patchy distributions, often driven by natural climate variability. For example, difficulties associated with assessing pelagic fish distributions have rendered fisheries management ill-equipped to adapt to the challenges posed by climate change, leaving pelagic species and ecosystems vulnerable. Here, we demonstrate the value of citizen science data for modelling the dynamic habitat suitability of a mobile pelagic predator (black marlin, Istiompax indica) within the south-west Pacific Ocean. The extensive spatial and temporal coverage of our occurrence data set (n = 18 717), collected at high resolution (~1.85 km(2) ), enabled identification of suitable habitat at monthly time steps over a 16-year period (1998-2013). We identified considerable monthly, seasonal and interannual variability in the extent and distribution of suitable habitat, predominately driven by chlorophyll a and sea surface height. Interannual variability correlated with El Nino Southern Oscillation (ENSO) events, with suitable habitat extending up to ~300 km further south during La Nina events. Despite the strong influence of ENSO, our model revealed a rapid poleward shift in the geometric mean of black marlin habitat, occurring at 88.2 km decade(-1) . By incorporating multiple environmental factors at monthly time steps, we were able to demonstrate a rapid distribution shift in a mobile pelagic species. Our findings suggest that the rapid velocity of climate change in the south-west Pacific Ocean is likely affecting mobile pelagic species, indicating that they may be more vulnerable to climate change than previously thought.


Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat.
1. Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite. 2. Diosmectite (500 mg x kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination. 3. Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B(4) synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg x kg(-1) day(-1)). 4. 5. Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells. Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells. 6. The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells. 7. Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.


Modification of the P-glycoprotein dependent pharmacokinetics of digoxin in rats by human recombinant interferon-alpha.
This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. Human recombinant IFN-alpha was given to rats (n = 5-7 per group) daily for 8 days at different doses (IntronA) 10(6), 2.10(6), or 4.10(6) IU kg(-1), s.c.), whereas pegylated-IFN-alpha (ViraferonPeg), 29 microg kg(-1)) was given s.c. three times a week. Rats were then given digoxin (32 microg kg(-1)) i.v. or orally. The pharmacokinetics of digoxin was studied. Intestinal P-gp expression was also examined. The pharmacokinetics of i.v. administered digoxin was not modified by IFN-alpha, but a dose-dependent increase in areas under the curve (AUCs) was observed in the orally administered digoxin parameters in rats (AUCs: 392 +/- 83 min microg L(-1), p < 0.01 and 550 +/- 97 min microg L(-1), p < 0.001, respectively, vs. 286 +/- 111 min microg L(-1) for control). A decrease in P-gp expression in the ileum (relative intensities: 0.70 +/- 0.19 for 4 Million International Unit (MIU) kg(-1) IFN-alpha-treated animals vs. 1.00 +/- 0.13 for controls, p < 0.05) and mainly in the jejunum (relative intensities: 0.46 +/- 0.13 for 4 MIU kg(-1) IFN-alpha-treated animals vs. 1.00 +/- 0.08 for controls, p < 0.001) was observed. IFN-alpha induces in vivo a significant dose-dependent inhibitory effect on intestinal P-gp activity related to a local decrease in its expression, thereby predicting important clinical consequences when IFN-alpha and other P-gp substrates are associated.


Flow cytometric analysis of the DNA profile of renal cell carcinoma.
DNA flow cytometry was applied to one hundred consecutive renal cell carcinomas from years 1974-1979. Single cell suspensions were prepared from paraffin-embedded tissue. From 96 evaluable tumours 34 were considered diploid and 62 aneuploid. Ploidy did not correlate statistically significantly with local growth, venous invasion, nodal or distant metastatic spread, or nuclear grade of renal cell carcinomas. Also the survival of the patients with diploid and aneuploid tumours was not significantly different, but, excluding patients with distant metastases at the time of extrafascial nephrectomy, 83% of the patients with diploid tumour survived for five years, while only 57% of the patients with aneuploid tumour were alive after the same time interval. The difference between survival curves is statistically almost significant (p less than 0.05). The cytologic nuclear grade predicted the prognosis more significantly (p less than 0.01), and the combination of these methods is recommended for the prognostication of renal cell carcinoma.


Electrochemical tagging of urate: developing new redox probes.
The electro-oxidation of uric acid in the presence of nucleophilic species is shown to produce conjugates that can aid our understanding of antioxidant interactions and also provide opportunities for advancing electroanalytical detection strategies involving purine species.


Spectroscopic characterization of different protonation/deprotonation states of Barbaloin in aqueous solution.
Barbaloin (10-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthraquinone: aloin A), present in Aloe species, is widely used in food, cosmetic and pharmaceutical industries. Here we characterize its optical absorption and emission spectra in aqueous solution at different pH values. Through pH titration, using both absorption and fluorescence spectroscopy, two pKa values for Barbaloin were determined: pKa1=9.6±0.6 and pKa2=12.6±0.8. These acidity constants were found to be higher than those found for Emodin, a similar molecule which lacks the sugar moiety present in Barbaloin. Performing quantum mechanical calculations for non-ionized, singly, doubly, and triply deprotonated forms of Barbaloin in vacuum and in water, we assigned the positions of the site for the first and third deprotonation in the anthraquinone group, and the second deprotonation in the glucose group. The instability of Barbaloin in high pH solutions is discussed here, and the optical absorption and fluorescence spectra due to products resulted from Barbaloin degradation at high pH is well separated from the Barbaloin original spectra. Biological fluids have specific pH values to maintain homeostasis, hence determining the pKa of Barbaloin is important to evaluate the mechanism of action of this drug in different parts of an organism as well as to predict pharmacological relevant parameters, such as absorption, distribution, metabolism, and excretion.


Laparoscopic orchiopexy for the high palpable undescended testis: preliminary experience.
We attempted to apply laparoscopic orchiopexy to the high palpable testis. Nine patients (12 testicles) were treated who ranged from 13 months to 13 years old. Laparoscopic techniques were used to mobilize the spermatic vessels and transfer the testis into the scrotum. Unilateral cases were completed in an average of 2.6 hours and bilateral cases in 3.0 hours with no complications. Tests maintained an intrascrotal position with no atrophy during a followup of 1 to 12 months. Laparoscopic orchiopexy for the high palpable undescended testis is possible with minimal morbidity and good short-term results.


[Morphologic changes of the digestive organs during the development of kidney failure].
Morphological changes in the organs of the gastrointestinal tract are caused by renal failure. They are reflected more in the small intestine and are accompanied by disturbance of the absorption process. The basis of these disorders are changes of the histoarchitecture of the absorbing surface of the small intestine.


Interpretable-ADMET: a web service for ADMET prediction and optimization based on deep neural representation.
In the process of discovery and optimization of lead compounds, it is difficult for non-expert pharmacologists to intuitively determine the contribution of substructure to a particular property of a molecule. In this work, we develop a user-friendly web service, named interpretable-absorption, distribution, metabolism, excretion and toxicity (ADMET), which predict 59 ADMET-associated properties using 90 qualitative classification models and 28 quantitative regression models based on graph convolutional neural network and graph attention network algorithms. In interpretable-ADMET, there are 250 729 entries associated with 59 kinds of ADMET-associated properties for 80 167 chemical compounds. In addition to making predictions, interpretable-ADMET provides interpretation models based on gradient-weighted class activation map for identifying the substructure, which is important to the particular property. Interpretable-ADMET also provides an optimize module to automatically generate a set of novel virtual candidates based on matched molecular pair rules. We believe that interpretable-ADMET could serve as a useful tool for lead optimization in drug discovery. Interpretable-ADMET is available at http://cadd.pharmacy.nankai.edu.cn/interpretableadmet/. Supplementary data are available at Bioinformatics online.


Evaluation of SLS: APG mixed surfactant systems as carrier for solid dispersion.
The present investigation aims at studying the effect of mixed surfactant system of sodium lauryl sulphate (SLS) and alkyl polyglucosides (C(10)APG, C(12)APG and C(12/14)APG) on dissolution rate enhancement of poorly water soluble drug. Aceclofenac--a non-steroidal anti-inflammatory agent was used as a model drug as it has limited water solubility. The influence of the surfactant concentration in various blends on dissolution rate of Solid Dispersion (SD), prepared using solution method with ethanol as the solvent was studied and the advantage of mixed surfactant systems over the individual surfactants was illustrated by differences in the in-vitro dissolution profiles of SD. Physico chemical evaluation (critical micellar concentration, zeta potential and beta-parameter calculations) was carried out to study the mixed surfactant systems. Solid mixtures were characterized by Infrared spectroscopy (FT-IR); X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). It was seen that the dissolution rate of aceclofenac from SD increased with the increase in the APG proportion relative to SLS with the optimum ratio of 0.2 SLS:0.8 APG showing the best effect in all cases. Results obtained from physico-chemical evaluation (the decrease in the value of critical micelle concentration and higher negative value of beta-parameters) suggested the existence of synergism between surfactants blends. The observed results in the dissolution rate enhancement could be attributed to the drug--surfactant interactions as evident from FT-IR, SEM and XRD results.


Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.
This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack. A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively). Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.


Electrochemical sensor based on biochar and reduced graphene oxide nanocomposite for carbendazim determination.
For the first time, a nanocomposite based on biochar and reduced graphene oxide (rGO) was employed to construct a modified carbon paste electrode and applied for the determination of carbendazim (CBZ). Biochar was obtained by through pyrolysis of Eichhornia crassipes biomass, also known how "Aguapé" at 400 °C. The modified electrode with our nanocomposite proposal shows to be able to preconcentrate CBZ and presented the highest analytical response in comparison to the unmodified electrode and by the electrodes prepared with the proposed materials separately. Using differential pulse voltammetry (DPV) under optimized conditions, the sensor showed a linear dynamic response (LDR) from 30 to 900 nmol L-1, a limit of detection (LOD) of 2.3 nmol L-1 and limit of quantification (LOQ) of 7.7 nmol L-1. No significant influence of inorganic ions or organic compounds on sensor response was verified, considering the recovery evaluation data. The proposed sensor was successfully applied for the determination of CBZ in spiked whole orange juice, lettuce leaves, drinking water, and wastewater samples. Good recovery values were found using the ex-situ methodology, showing excellent analytical performance of the electrochemical sensor based on biochar and rGO nanocomposite.


Repetitive part of the banana (Musa acuminata) genome investigated by low-depth 454 sequencing.
Bananas and plantains (Musa spp.) are grown in more than a hundred tropical and subtropical countries and provide staple food for hundreds of millions of people. They are seed-sterile crops propagated clonally and this makes them vulnerable to a rapid spread of devastating diseases and at the same time hampers breeding improved cultivars. Although the socio-economic importance of bananas and plantains cannot be overestimated, they remain outside the focus of major research programs. This slows down the study of nuclear genome and the development of molecular tools to facilitate banana improvement. In this work, we report on the first thorough characterization of the repeat component of the banana (M. acuminata cv. 'Calcutta 4') genome. Analysis of almost 100 Mb of sequence data (0.15× genome coverage) permitted partial sequence reconstruction and characterization of repetitive DNA, making up about 30% of the genome. The results showed that the banana repeats are predominantly made of various types of Ty1/copia and Ty3/gypsy retroelements representing 16 and 7% of the genome respectively. On the other hand, DNA transposons were found to be rare. In addition to new families of transposable elements, two new satellite repeats were discovered and found useful as cytogenetic markers. To help in banana sequence annotation, a specific Musa repeat database was created, and its utility was demonstrated by analyzing the repeat composition of 62 genomic BAC clones. A low-depth 454 sequencing of banana nuclear genome provided the largest amount of DNA sequence data available until now for Musa and permitted reconstruction of most of the major types of DNA repeats. The information obtained in this study improves the knowledge of the long-range organization of banana chromosomes, and provides sequence resources needed for repeat masking and annotation during the Musa genome sequencing project. It also provides sequence data for isolation of DNA markers to be used in genetic diversity studies and in marker-assisted selection.


Proliferation of erythroid colonies in semi-solid agar.
Growth of human erythroid cells in soft-agar culture with no added erythropoietin was demonstrated. This growth was particularly marked in patients with diseases such as myelofibrosis (MF) in which patients had a previous history of polycythaemia vera (PV) characterized by excessive red cell production. A rapid assessment of the proportion of erythroid colonies was obtained by directly staining the culture with benzidine. Fixed and stained preparations of these agar-grown cells revealed elements in all stages of erythroid maturation. The morphology of these erythroid colonies was characteristic of 'erythroblastic islands' containing central, iron-containing macrophages, surrounded by erythrocytic precursors, with the more mature erythrocytes found at the periphery of the colony. These observations document that erythropoiesis may be maintained in agar cultures, and suggest that this technique may be of diagnostic value in disease states characterized by abnormalities of red cell production.


Cost analysis of a novel HIV testing strategy in community pharmacies and retail clinics.
To document the cost of implementing point-of-care (POC) human immunodeficiency virus (HIV) rapid testing in busy community pharmacies and retail clinics. Providing HIV testing services in community pharmacies and retail clinics is an innovative way to expand HIV testing. The cost of implementing POC HIV rapid testing in a busy retail environment needs to be documented to provide program and policy leaders with adequate information for planning and budgeting. Cost analysis from a pilot project that provided confidential POC HIV rapid testing services in community pharmacies and retail clinics. The pharmacy sites were operated under several different ownership structures (for-profit, nonprofit, sole proprietorship, corporation, public, and private) in urban and rural areas. We included data from the initial six sites that participated in the project. We collected the time spent by pharmacy and retail clinic staff for pretest and posttest counseling in an activity log for time-in-motion for each interaction. Pharmacists and retail clinic staff. HIV rapid testing. The total cost was calculated to include costs of test kits, control kits, shipping, test supplies, training, reporting, program administration, and advertising. The six sites trained 22 staff to implement HIV testing. A total of 939 HIV rapid tests were conducted over a median time of 12 months, of which 17 were reactive. Median pretest counseling time was 2 minutes. Median posttest counseling time was 2 minutes for clients with a nonreactive test and 10 minutes for clients with a reactive test. The average cost per person tested was an estimated $47.21. When we considered only recurrent costs, the average cost per person tested was $32.17. Providing POC HIV rapid testing services required a modest amount of staff time and costs that are comparable to other services offered in these settings. HIV testing in pharmacies and retail clinics can provide an additional alternative venue for increasing the availability and accessibility of HIV testing services in the United States.


Investing in the Next Generation of Maternal and Child Health Leaders: The APHA Maternal and Child Health Section Student Fellows Program.
Practical experience in maternal and child health (MCH) settings is critical for professional development and learning. In 2002, the Maternal and Child Health (MCH) Section of the American Public Health Association (APHA) formalized its inclusion of students in section activities through the establishment of the Student Fellows Program. The Program provides graduate-level students opportunities to learn about MCH and APHA, build professional networks, and develop leadership skills. Since its inception, 18 cohorts of Fellows have benefited. This paper presents findings describing the Program from both written records about Fellow projects and activities recorded in past MCH Section communications as well as an online survey that was distributed to former and current Fellows to assess their perceptions and the benefits of the Student Fellows Program. Eighteen cohorts of Fellows have engaged with Section committees and working groups in diverse ways, including MCH-related research, policy, advocacy, and education. An online survey distributed to 151 participants was answered by 79 to document their perceptions of the Student Fellows Program. Of them, 56 (71%) indicated that the Program was important for their career development, 44 (55%) reported being current members of the APHA MCH Section, and 21 (27%) reported serving in a leadership position in the Section. The Fellows highlighted that networking, mentorship and leadership development were key benefits of the Student Fellows Program. After several years of involving students in its programs, the APHA MCH Section established the Student Fellows Program in 2002. The Fellows Program has been important for developing the next generation of MCH leaders. The findings suggest that this Program supports long-term interest and commitment to the field of MCH and contributed to the formation of leadership skills and behaviors of Fellows.


The effects of a glycogen loading regimen on acid-base status and blood lactate concentration before and after a fixed period of high intensity exercise in man.
Six healthy male subjects exercised after an overnight fast for a fixed 3 min period at a workload equivalent to 100% of their maximal oxygen uptake (VO2max) on 3 separate occasions. The first test took place after subjects had consumed a mixed diet (43 +/- 3% carbohydrate (CHO), 41 +/- 5% fat and 16 +/- 3% protein) for 3 days, and was followed 2 h later by prolonged cycling to exhaustion at 77 +/- 3% VO2max to deplete muscle glycogen stores. Following this, subjects consumed a low CHO diet (4 +/- 1% CHO, 63 +/- 5% fat and 33 +/- 6% protein) for the remainder of the day and for the subsequent 2 days; on the morning of the next day a second high intensity test took place. Finally subjects followed a 3 day high CHO diet (73 +/- 7% CHO, 17 +/- 6% fat and 10 +/- 1% protein) before their last test. Acid-base status and selected metabolites were measured on arterialized-venous blood at rest prior to exercise and at intervals for 15 min following exercise. Prior to exercise, plasma pH and blood lactate concentration were higher (p less than 0.05) after the high CHO diet when compared with the low CHO diet. Pre-exercise plasma bicarbonate, blood PCO2 and blood base excess were all higher after the high (p less than 0.001, p less than 0.01, p less than 0.01 respectively) and normal (p less than 0.05, p less than 0.05, p less than 0.05 respectively) CHO diets when compared with the low CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamics and the mesomorphic properties of a novel antiferroelectric liquid crystalline thiobenzoate MHPSBO10: thermal, optical and dielectric spectroscopy study.
The complementary studies of the mesomorphic properties of a novel antiferroelectric liquid crystal (AFLC) (S)-2-octile 4-S-(4'decyloxybiphenyl-4-tiocarboxy)benzoate, known under MHPSBO10 acronym have been undertaken. The polymorphism has been complementary studied in details by Differential Scanning Calorimetry (DSC), Transmitted Light Intensity (TLI) and Polarization Microscopy (POM). The switching characteristics along with multiple macroscopic parameters describing the mesomorphic properties were determined by using electro-optic measurements, both upon cooling and heating. Frequency domain dielectric spectroscopy (DS), covering a wide frequency range, has been applied to characterize the molecular motions. Several collective modes, including the low frequency processes in the condensed hexatic phase were detected, analyzed in details and followed with the temperature. The presented studies deliver a wide report of the phase transitions, molecular dynamics and the macroscopic properties of the novel antiferroelectric thiobenzoate.


Dietary guidance for the elderly.
General recommendations about nutritional adequacy and diets for health promotion must be adapted to the individual needs of elderly patients. Medical and nutritional status, food practices, and social and economic factors must be considered in providing nutritional care.


REIN: a tool at the service of the paediatric patients
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of paediatric CKD patients, the following key messages were retained. Paediatric stage 5 chronic kidney disease (CKD) has particularities that require to be analysed and taken into account because the mortality of these patients remains 30 times higher than that of children of the same age. The REIN registry enables illustrating the specificities of stage 5 CKD in the paediatric age-group in France and providing a set of indicators making it possible to describe the future of these patients as well as the choices made concerning the modalities of replacement therapy. As compared to other European countries, the incidence and prevalence of stage 5 CKD in France is in the middle range for children under 15 and 20 years old. Renal transplant is by far the leading treatment for stage 5 CKD in children and adolescents under 18 years of age in France, allowing to offer these patients the best possible life expectancy. Owing to the small volume of patients, only a nationwide registry can provide an unbiased view and enables analysing this population requiring a hyperspecialised treatment. The participation of French paediatric nephrologists in the REIN French registry also enables providing input to the European registry (ESPN/ERA www.espn-reg.org/index.jsp) and the international registry (IPNA https://ipna-registry.org) (Consulted on September 15th 2022) and thus the possibility of international studies, which are vital to be in line with an approach to improving practices.


Investigation on the pitting of potato starch granules during high frequency ultrasound treatment.
In this paper, the pitting of potato starch granules in aqueous suspensions (1%) by high-frequency high-power ultrasound (850kHz at a power of 0.2W, 2W or 3.7W; and also 500kHz and 1MHz at a power of 2W) is reported. The number of pits per starch granules was found to be independent of the amylose content of starches, and the surface properties of starch granules as modified through SDS and ethanol washing. At 850kHz, the maximum number of pits per starch granule, for both normal and waxy starches, did not exceed 11. However, a close inspection of fractionated starch granules based on their sizes showed that there is an optimum granule size for which a maximum pit number is obtained. For example, starch granules with diameter size range of ∼15 to ∼30μm had a maximum pit number (between 10 and 20 pits per granule) when sonicated (2W, 850kHz and 30min); while sonication of small (<10μm) and very large (>45μm) granules resulted in a smaller number of pits per granule (∼5). Further, the maximum number of pits per granules is also found to be proportional to the ultrasound frequency, with values of approximately 7, 10 and 11 at 0.50, 0.85, and 1MHz, respectively. FTIR measurements did not show any breakup of starch molecules.


Large left atrial appendage predicts the ablation outcome in hypertensive patients with atrial fibrillation.
Clinical outcomes of patients with atrial fibrillation (AF) undergoing catheter ablation can be influenced by many factors. This study sought to investigate whether left atrial appendage (LAA) volume can predict the recurrence of AF after catheter ablation in hypertensive patients. 108 hypertensive patients(aged 63.1 ± 8.1 years, 53.7% male) with paroxysmal or persistent AF undergoing a first catheter ablation were retrospectively evaluated. Contrast-enhanced cardiac computed tomography (CT) was performed in all enrolled patients prior to ablation for assessment of LAA volume and left atrium (LA) anatomy. Patients were followed up for 12 months to analyze the clinical outcomes after AF catheter ablation. 24 patients had AF recurrence after a mean follow-up of 12 months. Patients with AF recurrence (24, 22.2%) exhibited significantly larger (longer) LAA volume, LAA orifice area, LAA orifice short axis, LA volume, LA diameter and higher level of N-terminal proB-type natriuretic peptide (NT-proBNP) compared to those without AF recurrence. LAA volume correlated with type of AF, LA volume, LA diameter and the level of NT-proBNP. Multiple regression analysis demonstrated that LAA volume was an independent predictor of post-ablation AF recurrence in hypertensive patients. Furthermore, LAA volume > 9.99 ml served as a valuable independent predictor of AF recurrence, with a sensitivity of 83.3% and a specificity of 66.7% (area under the curve = 0.733). LAA volume derived from cardiac CT was an independent predictor of AF recurrence after catheter ablation in hypertensive patients.


Utility of the Neurobehavioral Symptom Inventory Validity-10 index to detect symptom exaggeration: An analogue simulation study.
The Neurobehavioral Symptom Inventory (NSI) has been recommended by the interagency Traumatic Brain Injury (TBI) Outcome Workgroup as an outcome measure for TBI research. A new symptom exaggeration index-the NSI Validity-10-can be calculated from its items, but its utility has not been evaluated in a malingering simulation study. Data from a prior analogue study were reanalyzed to examine the NSI Validity-10 test properties. The data were from a sample of 85 Australian undergraduate students. A battery of measures was completed under 1 of 3 experimental conditions: control (i.e., honest responding, n = 24), feign postconcussional disorder (PCD; n = 29), and feign posttraumatic stress disorder (PTSD; n = 32). Participants who feigned PTSD or PCD had significantly higher scores on the NSI Validity-10 compared with controls. There were minimal differences between the 2 feigning groups. Using the combined data from the feigning groups and assuming a 35% symptom exaggeration base rate, the optimal NSI Validity-10 cutoff score was ≥10. This cutoff score identified "probable exaggeration" (sensitivity = .75, specificity = 1.0, positive predictive power = 1.0, negative predictive power = .88). Diagnostic efficiency statistics for 25% and 45% base rates were also generated. The cutoff score identified in this study is lower than previously reported. Its properties are promising, but its usage requires careful consideration.


Peripheral lung adenocarcinomas: 10 mm or less in diameter.
Few reports have been published regarding peripheral lung adenocarcinomas that are 10 mm or less in diameter. This is considered to be the smallest tumor size detectable by present diagnostic modalities. Clinicopathologic studies were performed in 57 patients with peripheral lung adenocarcinomas of 10 mm or less in diameter. Outcomes were compared with two other groups that consisted of 32 patients with adenocarcinomas between 11 and 15 mm in diameter and 35 patients with adenocarcinomas between 16 and 20 mm in diameter. Tumors were curatively resected between 1992 and 2002. The mean age was 61.7 years. The following three features were more frequent: female sex (78.9%), nonsmokers (77.2%), and cases with carcinoma detected by computed tomography despite negative chest radiography (96.5%). Negative lymphatic invasion (94.7%) was significantly higher. Three cases showed lymphatic invasion that was classified as types E or F, according to Noguchi's classification. There were no cases of lymph node metastasis, pleural involvement, or intrapulmonary metastasis. Well-differentiated type was in 93.0%. Types A and B, which are noninvasive alveolar replacement-type adenocarcinomas, were significantly dominant (86.0%). The 5-year postoperative survival rate was 97.3%, which was significantly better than in the other two groups (75.5%, 78.1%). Histopathologic features of most peripheral lung adenocarcinomas of 10 mm or less in diameter were types A and B. Types A and B were considered fundamentally indicated for thoracoscopic wedge resections. However, the other types required the standard operation.


Obesity, stress, and smoking: their role as cardiovascular risk factors in women.
Obesity, defined as an increase of 20% or more above desired weight, has been found to be an independent, albeit weak, risk factor for coronary heart disease in women and may increase the relative risk of other factors such as hypertension, diabetes mellitus, and elevated total serum cholesterol and low-density lipoprotein-cholesterol. Type A personality and stress, on the other hand, appear to be moderate risk factors for coronary heart disease in women as well as in men. Approximately twice as many cardiovascular events occurred in type A women 35 to 64 years old as in type B women of the same age group. As expected, cigarette smoking is a major risk factor, primarily in young women. Women with smoking patterns similar to those of men experience similar rates of cardiovascular morbidity and mortality. In addition, smoking apparently acts synergistically with oral contraceptives and elevated total serum cholesterol to further increase risk.


Increased plasma bile alcohol glucuronides in patients with cerebrotendinous xanthomatosis: effect of chenodeoxycholic acid.
Large quantities of C27 bile alcohols hydroxylated at C-25 are excreted in the bile and urine of patients with cerebrotendinous xanthomatosis, a lipid storage disease that results from defective bile acid synthesis. The presence of both biliary and urinary bile alcohols reflects impaired bile acid synthesis. After treatment of samples with beta-glucuronidase, plasma bile alcohols were quantitated by gas-liquid chromatography-mass spectrometry. 5 beta-Cholestane-3 alpha,7 alpha,12 alpha,25-tetrol (334 micrograms/dl) was found to be the major bile alcohol, followed by 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23R,25-pentol (65 micrograms/dl), and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24(R and S),25-pentols (62.5 micrograms/dl and 64.5 micrograms/dl, respectively) in the plasma of these patients. When compared to biliary and urinary bile alcohol excretions, the plasma pattern resembled bile where 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol glucuronide predominated. In contrast, urinary bile alcohols were composed chiefly of 5 beta-cholestanepentol glucuronides with only small amounts of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol glucuronide. Treatment with chenodeoxycholic acid, which suppresses abnormal bile acid synthesis in these patients, reduced plasma bile alcohol concentrations dramatically. These results show that large quantities of bile alcohol glucuronides, particularly 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrolglucuronide, circulate in plasma of patients with cerebrotendinous xanthomatosis. The plasma bile alcohols closely resemble biliary bile alcohols which indicates their hepatic origin. The large quantities of polyhydroxylated bile alcohols in the urine may suggest their formation, at least in part, from 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol by renal hydroxylating mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolutionary Approach to Biological Homochirality.
We study a very simple linear evolutionary model based on distribution of protocells by total enantiomeric excess and without any mutual inhibition and show that such model can produce two species with values of total enantiomeric excess in each of the species approaching [Formula: see text] when there is a global [Formula: see text] symmetry. We then consider a scenario when there is a small external global asymmetry factor, like weak interaction, and show that only one of the species remains in such a case, and that is the one, which is more efficient in replication. We perform an estimate of the time necessary to reach homochirality in such a model and show that reasonable assumptions lead to an estimate of around 300 thousand years plus or minus a couple of orders of magnitude. Despite this seemingly large time to reach homochirality, the model is immune to racemization because amino acids in the model follow the lifespan of the protocells rather than the time needed to reach homochirality. We show that not needing mutual inhibition in such evolutionary model is due to the difference in the topology of the spaces in which considered model and many known models of biological homochirality operate. Bifurcation-based models operate in disconnected zero-dimensional space (the space is just two points with enantiomeric excess equal [Formula: see text] and [Formula: see text]), whereas considered evolutionary model (in its continuous representation) operates in one-dimensional connected space, that is the whole interval between [Formula: see text] and [Formula: see text] of total enantiomeric excess. We then proceed with the analysis of the replication process in non-homochiral environment and show that replication errors (the probability to attach an amino acid of wrong chirality) result in a smooth decrease of replication time when total enantiomeric excess of the replicated structure moves away from zero. We show that this decrease in replication time is sufficient for considered model to work.


Intimate Partner Violence Associated with Postpartum Depression, Regardless of Socioeconomic Status.
Objective This study examined whether socioeconomic status moderated the association between intimate partner violence (IPV) and postpartum depression among a community-based sample of women. Defining the role of poverty in the risk of postpartum depression for IPV victims enables prioritization of health promotion efforts to maximize the effectiveness of existing maternal-infant resources. Methods This cross-sectional telephone-survey study interviewed 301 postpartum women 2 months after delivery, screening them for IPV and depression [using Edinburgh Postnatal Depression Scale (EPDS)]. Socioeconomic status was defined by insurance (Medicaid-paid-delivery or not). This analysis controlled for the following covariates, collected through interview and medical-record review: demographics, obstetric history, prenatal health and additional psychosocial risk factors. After adjusting for significant covariates, multiple linear regression was conducted to test whether socioeconomic status confounded or moderated IPV's relationship with EPDS-score. Results Ten percent of participants screened positive for postpartum depression, 21.3 % screened positive for current or previous adult emotional or physical abuse by a partner, and 32.2 % met poverty criteria. IPV and poverty were positively associated with each other (χ(2) (1) = 11.76, p < .001) and with EPDS score (IPV: beta 3.2 (CI 2.0, 4.5) p < .001, poverty: beta 1.3 (CI 0.2, 2.4) p = .017). In the multiple linear regression, IPV remained significantly associated, but poverty did not (IPV: adjusted beta 3.1 (CI 1.8, 4.3) p < .001, poverty: adjusted beta 0.8 (CI -0.3, 1.9) p = .141), and no statistically significant interaction between IPV and poverty was found. Conclusions Study findings illustrated that IPV was strongly associated with postpartum depression, outweighing the influence of socioeconomic status upon depression for postpartum women.


Nuclear and cell area measurements in the cytological evaluation of pleural effusions: a study of subjective assessments and morphometric measurements.
Morphometric measurements of cellular area, nuclear area and nuclear:cytoplasmatic ratio were performed on single cells in pleural effusions from 15 patients with effusion caused by bronchial, ovarian, or mammary carcinoma. The results were compared with corresponding measurements on mesothelial cells in pleural effusions from 15 patients without malignant disease. Significant differences were found between the mean values from cellular area, nuclear area, and nuclear:cytoplasmatic ratios in mesothelial cells from benign effusion versus malignant cells from effusions associated with metastatic growth. Such morphometric measurements are, however, of little value in routine diagnostic work as more than 90% of the cells in the two groups showed similar values.


Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans.
OATP1B3/SLCO1B3 is a human liver-specific transporter for the clearance of endogenous compounds (eg, bile acid [BA]) and xenobiotics. The functional role of OATP1B3 in humans has not been characterized, as SLCO1B3 is poorly conserved among species without mouse orthologs. Slc10a1-knockout (Slc10a1-/-), Slc10a1hSLCO1B3 (endogenous mouse Slc10a1 promoter-driven human-SLCO1B3 expression in Slc10a1-/- mice), and human SLCO1B3 liver-specific transgenic (hSLCO1B3-LTG) mice were generated and challenged with 0.1% ursodeoxycholic-acid (UDCA), 1% cholic-acid (CA) diet, or bile duct ligation (BDL) for functional studies. Primary hepatocytes and hepatoma-PLC/RPF/5 cells were used for mechanistic studies. Serum BA levels in Slc10a1-/- mice were substantially increased with or without 0.1% UDCA feeding compared with wild-type (WT) mice. This increase was attenuated in Slc10a1hSLCO1B3-mice, indicating that OATP1B3 functions as a significant hepatic BA uptake transporter. In vitro assay using primary hepatocytes from WT, Slc10a1-/-, and Slc10a1hSLCO1B3-mice indicated that OATP1B3 has a similar capacity in taking up taurocholate/TCA as Ntcp. Furthermore, TCA-induced bile flow was significantly impaired in Slc10a1-/- mice but partially recovered in Slc10a1hSLC01B3-mice, indicating that OATP1B3 can partially compensate the NTCP function in vivo. Liver-specific overexpression of OATP1B3 markedly increased the level of hepatic conjugated BA and cholestatic liver injury in 1% CA-fed and BDL mice. Mechanistic studies revealed that conjugated BAs stimulated Ccl2 and Cxcl2 in hepatocytes to increase hepatic neutrophil infiltration and proinflammatory cytokine production (eg, IL-6), which activated STAT3 to repress OATP1B3 expression by binding to its promoter. Human OATP1B3 is a significant BA uptake transporter and can partially compensate Ntcp for conjugated BA uptake in mice. Its downregulation in cholestasis is an adaptive protective response.


A maternal diet rich in fish oil may improve cardiac Akt-related signaling in the offspring of diabetic mother rats.
Newborns of diabetic mothers have abnormal circulatory organs, so in this study, we explore insulin signaling in the newborn rat heart. Pregnant rats were divided into streptozotocin-induced diabetic groups (DM) and control groups (CM). Rats were fed lard (21% fat), fish oil (21% fat), or a control diet (7% fat). To examine changes in insulin signaling in the hearts of infants of diabetic mothers (IDM) in relation to diet, we isolated the hearts from the IDM and control infants and determined the phosphorylation levels of Akt308, Akt473, p38, c-jun-NH2-terminal protein kinase (JNK), and extracellular signal-regulated protein kinase (ERK), and the expression levels of phosphoinositide-dependent protein kainase1 (PDK1) and mammalian target of rapamycin (mTOR). The mean blood glucose levels in the DM group and their infants were significantly higher than those in the CM group (P < 0.05) and their infants (P < 0.05), but the mean blood glucose levels of all infants was normal on postnatal d 4. Phosphorylation levels of Akt (Thr 308) (P < 0.05) and Akt (Ser 473) and the expression levels of PDK1 and mTOR were lower in infants of diabetic mothers (IDM) than in control infants. The phosphorylation level of Akt (Ser 473) and the expression level of mTOR increased in IDM fed the fish oil diet compared with those fed the lard diet (P < 0.05). A maternal diet rich in fish oil improves cardiac Akt-related signaling in the offspring of diabetic rats.


Absolute renal blood flow quantification by dynamic MRI and Gd-DTPA.
The aim of this study was to demonstrate the feasibility of the absolute renal blood flow quantification using MRI and injection of contrast media. Using a T1-weighted fast gradient sequence following an intravenous bolus injection of Gd-DTPA, dynamic images of the kidney were obtained in patients with well-functioning native kidneys (n = 7) or transplant (n = 9), with significant renal artery stenosis (n = 4) and with renal failure (n = 7). After signal intensity calibration, the absolute renal perfusion was equal to the wash-in slope of the renal transit curve divided by the contrast medium concentration at the peak of the bolus in the aorta. The cortical blood flow was 2.54+/-1.16 ml/min per gram in well-functioning kidneys decreasing to 1.09+/-0.75 ml/min per gram in case of renal artery stenosis (p = 0.04) and to 0.51+/-0.34 ml/min per gram in case of renal failure (P<0.001). These measurements were in agreement with previous results obtained by other methods. A standard MRI imaging sequence and a simple model can provide realistic quantitative data on renal perfusion. This work justifies further studies to compare this model with a gold standard for renal blood flow measurements.


Protons extruded by NHE1: digestive or glue?
Many physiological and pathophysiological processes, such as embryogenesis, immune defense, wound healing, or metastasis, are based on cell migration and invasion. The activity of the ubiquitously expressed NHE1 isoform of the plasma membrane Na(+)/H(+) exchanger is one of the requirements for directed locomotion of migrating cells. The mechanisms by which NHE1 is involved in cell migration are multiple. NHE1 contributes to cell migration by affecting the cell volume, by regulating the intracellular pH and thereby the assembly and activity of cytoskeletal elements, by anchoring the cytoskeleton to the plasma membrane, by the organization of signal transduction and by regulating gene expression. The present review focuses on two additional, extracellular mechanisms by which NHE1 activity contributes to cell migration and invasion. Protons extruded by the NHE1 lead to local, extracellular acidification which, on the one hand, can create pH optima needed for the activity of proteinases at invadopodia/podosomes necessary for extracellular matrix digestion and, on the other hand, facilitates cell/matrix interaction and adhesion at the cell front.


Characterisation of sleep disturbances in postural orthostatic tachycardia syndrome: a polysomnography-based study.
Postural orthostatic tachycardia syndrome (PoTS) has been frequently associated with sleep disturbances but objective sleep data are lacking. In addition, although regional autonomic denervation has been described, less is known about autonomic nervous activity overnight in these patients. A full polysomnography and heart rate variability were performed on 37 patients diagnosed with PoTS . In addition, a multiple sleep latency test (MSLT) was conducted on a subgroup of patients with excessive daytime sleepiness. The polysomnographic data did not show major pathological findings except the percentage spent in rapid eye movement (REM) sleep which was slightly reduced at 18.4%. The MSLT did not confirm excessive daytime sleepiness as median mean sleep latency was 14.4 min (11.8-17.5). When comparing patients with and without subjective daytime sleepiness, it was found that the latter had a reduced parasympathetic activation at night as expressed by the average high frequency [6936.5 ms(2) (6028.2-8675.5) vs. 4689.5 (3922.7-7685.2) p < 0.05]. Patients with PoTS do not exhibit polysomnographic findings consistent with relevant sleep pathologies nor objective daytime sleepiness. Subjective daytime sleepiness is associated with enhanced activation of the parasympathetic nervous system.


Environmental magnetic parameter characteristics as indicators of heavy metal pollution in the surface sediments off the Zhoushan Islands in the East China Sea.
The pollution of continental shelf sea sediments has always been an important issue for scientists because it can directly affect marine life and marine ecology. Thus, we carried out detailed studies of environmental magnetism and heavy metals in 145 surface sediment samples from the area southeast of the Zhoushan Islands in the East China Sea. The magnetic minerals in the sediments are mainly magnetite with a small amount of goethite and hematite. The magnetic mineral particles are mainly pseudosingle domain and contain a certain amount of superparamagnetic particles. The distribution of the magnetic mineral content shows a gradual decreasing trend from land to sea, which is closely related to the sediment transport pattern. The anhysteretic remanent magnetization (χARM) and χARM ratio to magnetic susceptibilities (χARM/χ) were more sensitive than other indexes to sediment pollution and could be used as indicators for environmental pollution in the nearshore area. Additionally, a correlation analysis with the major elements showed that the χARM ratio to saturation isothermal remanence (χARM/SIRM) can well explain the sources of terrigenous sediment. Therefore, the environmental magnetic parameters in the continental shelf area can be used as a precursor for geochemical research and provide data support for further research.


Mannose receptor contribution to Candida albicans phagocytosis by murine E-clone J774 macrophages.
Mannoproteins, as the main constituents of the outer layer of yeast cell walls, are able to interact with phagocytic cells in an opsonin-independent manner through the mannose receptor (MR) and to induce yeast ingestion by the professional phagocytes. Moreover, the MR also mediates endocytosis of soluble ligands through clathrin-coated pits. Here, we studied some aspects of the interaction between the MR and Candida albicans using murine E-clone macrophages and the consequences on MR trafficking. Using a pull-down assay involving mixture E-clone macrophage detergent lysate with mannosylated Sepharose beads and glutaraldehyde-fixed, heat-killed (HK) C. albicans, we found that binding of solubilized MR to mannosylated particles occurred with characteristics similar to the receptor's cell-surface mannose-binding activity. We then demonstrated that MR expressed on E-clone macrophages contributed to phagocytosis of unopsonized, HK C. albicans and that yeast phagocytosis induced a decrease in MR endocytic activity without concomitant degradation of the receptor in the time lapse studied.


"Epileptic" brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies.
Sustained electrical stimulation of the perforant path in urethane-anesthetized rats evoked hippocampal granule cell population spikes and epileptiform discharges. After stimulation, recurrent inhibition in the granule cell layer was abolished. Light microscopic analysis revealed a highly reproducible pattern of hippocampal damage to dentate pyramidal basket cells, hilar cells in general and CA3 and CA1 pyramidal cells. CA2 pyramidal cells and dentate granule cells were relatively unaffected. When perforant path stimulation on one side of the brain evoked bilateral granule cell discharges, damage was bilateral. Unilateral hippocampal seizures were associated with unilateral hippocampal damage. Rapid Golgi-stained hippocampi exhibited spherical dendritic swellings at the sites of termination of excitatory entorhinal afferents to the hippocampus and in the mossy fiber region. Electrical stimulation of a single excitatory afferent to the hippocampus appears to reproduce the "epileptic" pattern of hippocampal damage without using convulsant drugs and without causing motor convulsions. It is suggested that seizure-associated brain damage is caused by excessive pre-synaptic release of excitatory transmitter that induces intracellular post-synaptic changes that lead to dendritic swelling and cell death.


[Antiinflammatory and antiulcer effect of oxymethyluracil].
Enteral administration of oxymethyluracil in non-inbred albino rats decreased the inflammatory reaction to histamine, serotonin, bradykinin, carrageenan and trypsin, (being similar to voltaren) and reduced granulomatous inflammation, but influenced the proliferation to a lower extent than did voltaren. In contrast to voltarcen, oxymethyluracil also exhibited gastroprotective antiulcer properties.


[Sulindac suppositories: treatment of pain in osteoarthritis (author's transl)].
Thirty one patients with osteoarthritis (29 hips, 16 knees) were submitted to a treatment with sulindac at a daily dose of 200 mg bid suppositories during four weeks. This trial showed that the treatment brought relief of pain in the majority of patients. Compared with others previously prescribed drugs, sulindac was more effective (72%). Sulindac suppositories were well tolerated; only three drop-out because side-effects (gastro intestinal tract: 2, skin 1) have been reported. Sulindac suppositories tolerance was reported as good.


Linkage studies of Myotonia congenita and Paramyotonia congenita.
Six German families segregating for Myotonia congenita (MC) and eight families from Germany and Great Britain with Paramyotonia congenita (PC) were tested for linkage relationships using 35 serological and biochemical markers. No linkage of MC to any of the markers was evident, but a positive sum of lod scores for PC vs. the HP locus (z = 1.16, theta = 0.16) was found. The results encourage further investigations involving chromosome 16 markers.


Correlated expression of a B-lymphocyte-specific glycoprotein (gp27/35) and the EBV receptor/C3 receptor complex in sublines from the same Burkitt lymphoma.
A series of virus-producer and non-producer sublines, derived from the Burkitt lymphoma line Jijoye and its P3HR-1 clone, were previously found to differ in the expression of EBV receptors and, in parallel, C3 receptors. The differences could be related to an "internal selection" caused by the cytopathic P3HR-1 virus variant, favouring the growth of receptor-negative cells. We have now analyzed the same lines for the expression of a B-lymphocyte-specific glycoprotein (gp27/35). A close parallellism was found between the expression of the EBV receptor-complement receptor complex and the glycoprotein, measured by quantitative absorption. The results favour a relationship between gp27/35 and EBV/C3 receptor expression.


Patient and physician factors associated with symptomatic undiagnosed asthma or COPD.
It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD. Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD. Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97). Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.


Neuroactive effects of cotinine on the hippocampus: behavioral and biochemical parameters.
The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHβE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.


On the production of low tongue tip /s/: a case report.
X-ray motion pictures and electromyography were combined to record tongue movement and tongue muscle activity of a normal speaker during /s/ production. The /s/ was in /i/, /alpha/, and /u/ vowel environments and in two and three consonant clusters. Lead pellets attached to the tongue tip and dorsum were tracked by frame-by-frame analysis of the X-ray film. Recordings from the tongue muscles were graphed and compared with the movement data. Results demonstrate that this subject produces /s/ with the tongue tip down behind the lower incisors and the blade elevated toward the alveolar ridge. EMG data from the tongue shows that the tongue tip depression is not passive but is an active part of the motor strategy used by this subject to elevate the tongue body. These findings suggest that speech pathologists might well include the tip-down strategy of /s/ production in the therapeutic process as an alternative to the tip-up /s/.


Epidemiology of venous thromboembolism in cardiorespiratory and infectious disease.
Venous thromboembolic complications -- deep vein thrombosis and pulmonary embolism -- occur in a significant proportion of hospitalized medical patients. The incidence in acutely ill medical patients is 10%-40%, equivalent to that seen in general surgical patients. Prophylaxis is effective and well tolerated, yet remains under-prescribed in medical wards. Current recommendations for prophylaxis are generalized and do not specifically address many patient groups. Data on the prevalence in patients with chronic obstructive pulmonary disease, heart failure, and infectious diseases are limited. However, studies on large numbers of hospitalized patients with these admission diagnoses have provided important information on incidence, and the efficacy of thromboprophylaxis. This review summarizes current knowledge of the epidemiology of venous thromboembolism in patients with chronic obstructive pulmonary disease, heart failure, and infectious diseases, and highlights the benefits of, and needs for, appropriate prophylaxis in these groups. Increased awareness of the prevalence of thrombosis in the major subgroups of medical inpatients should improve the prescribing of prophylaxis and prevent potentially avoidable and costly complications.


The cellular origin of lysosomal enzymes in the plaque in multiple sclerosis. II. A histochemical study with combined demonstration of myelin and acid phosphatase.
Existing techniques have been adapted and it has been possible to demonstrate acid phosphatase (APP) and myelin, lipid or astrocytic fibres in the same histological section. In normal controls APP was demonstrated in neurons, astrocytes, ependyma including choroid plexus epithelium and in pericytes, but not in oligodendrocytes. In multiple sclerosis (MS), APP positive cells were found in the plaque, plaque edge and macroscopically normal white matter. Contrary to some previous reports, not only macrophages, but also astrocytes in the MS plaque were found to be APP positive, although the distribution of enzyme in these cells was predominantly diffuse, unlike the particulate distribution in normal astrocytes and other APP positive cells: the significance of this finding is discussed. It is concluded that astrocytes and macrophages are the main source of the elevated levels of APP found biochemically in MS and that in old plaques astrocytes make the major contribution.


Venous thromboembolism risk stratification in trauma using the Caprini risk assessment model.
The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients. We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Multiple logistic regression assessed odds of inpatient VTE. A total of 1279 patients met study eligibility, with a total of 33 VTE (2.6%). When comparing those with VTE to those without, the mean age was lower (52.5 vs 59.5, p = 0.06, respectively), sex distribution was similar, but mean body mass index was higher (30.2 vs 27.4, p = 0.019, respectively). The mean Caprini score was 9.9, and 75.5% had a score >4, the traditional Caprini high-risk cutoff. The VTE group had a higher mean Injury Severity Score (17.8 vs 12.6, p = 0.011), and mean Caprini score (16.4 vs 9.8, p < 0.001). Multiple logistic regression found Caprini score, not Injury Severity Score, was associated with higher odds of VTE (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.10), after adjusting for Injury Severity Score, any missed doses of VTE chemoprophylaxis, and VTE prophylaxis type. Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. These data support using the Caprini risk assessment model in the trauma population, which may aid in risk stratification.


No difference in revision risk between autologous hamstring graft less than 8 mm versus hybrid graft 8 mm or larger in anterior cruciate ligament reconstruction.
Hamstring autograft (HA) is commonly used for primary anterior cruciate ligament reconstruction (ACLR). However, if the harvested HA is inadequate in diameter, it is often augmented with an allograft tendon, forming a hybrid graft (HY). This study sought to evaluate aseptic revision risk following HA versus HY ACLR. A retrospective cohort study was performed using data obtained from our healthcare system's ACLR registry. Patients ≤ 25 years of age who underwent primary isolated ACLR were identified (2005-2020). Graft type and diameter size was the primary exposure of interest: < 8 mm HA and ≥ 8 mm HY. A secondary analysis was performed to examine 7 mm HA and 7.5 mm HA vs ≥ 8 mm HY. Propensity score-weighted Cox proportional hazard regression was used to evaluate the risk of aseptic revision. The study sample included 1,945 ACLR: 548 ≥ 8 mm HY, 651 7 mm HA, and 672 7.5 mm HA. The crude cumulative aseptic revision probability at 8-years for ≥ 8 mm HY was 9.1%, 11.1% for 7 mm HA, and 11.2% for 7.5 mm HA. In adjusted analysis, no difference in revision risk was observed for < 8 mm HA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.72-1.82), 7 mm HA (HR 1.23, 95% CI 0.71-2.11), or 7.5 mm HA (HR 1.16, 95% CI 0.74-1.82) compared to ≥ 8 mm HY. In a US-based cohort of ACLR patients aged ≤ 25 years, we failed to observe any differences in aseptic revision risk for HA < 8 mm compared to HY ≥ 8 mm. Augmentation of a HA as small as 7 mm is not necessary to prevent a revision surgery. Level III.


Representations of mad cow disease.
This paper examines the reporting of the story of Bovine Spongiform Encephalopathy (BSE) and its human derivative variant Creutzfeld-Jacob Disease (vCJD) in the British newspapers. Three 'snapshots' of newspaper coverage are sampled and analysed between the period 1986 and 1996 focusing on how representations of the disease evolved over the 10-year period. Social representations theory is used to elucidate how this new disease threat was conceptualised in the newspaper reporting and how it was explained to the UK public. This paper examines who or what was said to be at risk from the new disease, and whether some individuals or groups held to blame for the diseases' putative origins, the appearance of vCJD in human beings, and its spread.


A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity.
Cdc7 is an essential kinase that promotes DNA replication by activating origins of replication. Here, we characterized the potent Cdc7 inhibitor PHA-767491 (1) in biochemical and cell-based assays, and we tested its antitumor activity in rodents. We found that the compound blocks DNA synthesis and affects the phosphorylation of the replicative DNA helicase at Cdc7-dependent phosphorylation sites. Unlike current DNA synthesis inhibitors, PHA-767491 prevents the activation of replication origins but does not impede replication fork progression, and it does not trigger a sustained DNA damage response. Treatment with PHA-767491 results in apoptotic cell death in multiple cancer cell types and tumor growth inhibition in preclinical cancer models. To our knowledge, PHA-767491 is the first molecule that directly affects the mechanisms controlling initiation as opposed to elongation in DNA replication, and its activities suggest that Cdc7 kinase inhibition could be a new strategy for the development of anticancer therapeutics.


Expression of an acyl-CoA synthetase, lipidosin, in astrocytes of the murine brain and its up-regulation during remyelination following cuprizone-induced demyelination.
Lipidosin is an 80-kDa protein with long-chain acyl-CoA synthetase activity expressed in the brain, adrenal gland, testis, and ovary, which are selectively damaged in X-linked adrenoleukodystrophy (X-ALD). Western blot analysis of the cerebrum and cerebellum revealed a gradual increase in the expression of lipidosin postnatally. Light microscopic immunohistochemistry using a panel of specific monoclonal antibodies showed that the lipidosin-immunopositive cells were ubiquitously distributed in the brain and were denser in the gray matter than in the white matter. Lipidosin immunoreactivity was colocalized with GFAP immunoreactivity but not with ubiquitin C-terminal hydrolase 1 (= PGP9.5) immunoreactivity, a neuronal marker, and lipidosin-producing cells detected by an antisense probe specific for lipidosin mRNA were also GFAP immunopositive. These data together with Western blot analysis of primary cultured astrocytes indicate that lipidosin is expressed in astrocytes. Immunoelectron microscopic analysis revealed that lipidosin immunoreactivity was widely distributed from perivascular endfeet to perisynaptic processes without being limited to peroxisomes. Lipidosin immunoreactivity was greatly increased in astrocytes in the area of remyelination following experimental demyelination induced by the administration of cuprizone to mice. These data suggest that lipidosin was involved in fatty acid metabolism during reconstruction of the myelin sheath.


A nested cohort 5-year Canadian surveillance of Gram-negative antimicrobial resistance for optimized antimicrobial therapy.
We analyzed 5 years (2016-2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and antimicrobial resistance (AMR) patterns of adult Gram-negative infections in Canadian health care and to complement other public surveillance programs and studies in Canada. A total of 6853 isolates were analyzed from medical (44%), surgical (18%), intensive care (22%) and emergency units (15%) and from respiratory tract (36%), intra-abdominal (25%), urinary tract (24%) and bloodstream (15%) infections. Overall, E. coli (36%), P. aeruginosa (18%) and K. pneumoniae (12%) were the most frequent isolates and P. aeruginosa was the most common respiratory pathogen. 18% of Enterobacterales species were ESBL positive. Collective susceptibility profiles showed that P. aeruginosa isolates were highly susceptible (> 95%) to ceftolozane/tazobactam and colistin, though markedly less susceptible (58-74%) to other antimicrobials tested. Multi-drug resistance (MDR) was present in 10% of P. aeruginosa isolates and was more frequent in those from respiratory infections and from ICU than non-ICU locations. Of P. aeruginosa isolates that were resistant to combinations of ceftazidime, piperacillin/tazobactam and meropenem, 73-96% were susceptible to ceftolozane/tazobactam over the period of the study. These national data can now be combined with clinical prediction rules and genomic data to enable expert antimicrobial stewardship applications and guide treatment policies to optimize adult patient care.


Investigation of genotoxic and antigenotoxic activities of Melampodium divaricatum in Salmonella typhimurium.
Melampodium divaricatum is a member of the Asteraceae and in Brazil is known as false-calendula, its flowers being used in anti-inflammatory preparations, substituting the true calendula or marigold (Calendula officinalis L.). The flower extract was investigated for mutagenic and antimutagenic effect in the Salmonella/microsome assay. The tested extract was not mutagenic in the strains TA100, TA98, TA97a and TA102 and decreased the mutagenicity of aflatoxin B1, benzo(a)pyrene and daunomycin. Chlorophyll and triterpenes were detected in the extract, and they might have contributed to the observed effect. Our data suggest that these medicinal plants possess cancer chemopreventive properties.


Reliability based geometrically nonlinear bi-directional evolutionary structural optimization of elasto-plastic material.
The aim of this paper is to integrate the reliability-based analysis into topology optimization problems. Consequently, reliability-based topology optimization (RBTO) of geometrically nonlinear elasto-plastic models is presented. For purpose of performing (RBTO), the volume fraction is considered reliable since that the application of (RBTO) gives different topology in comparison to the deterministic topology optimization. The effects of changing the prescribed total structural volume constraint for deterministic designs and changing the reliability index for probabilistic designs are considered. Reliability index works as a constraint which is related to reliability condition added into the volume fraction and it is calculated using the Monte-Carlo simulation approach in the case of probabilistic design. In addition, bi-directional evolutionary structural optimization (BESO) method is utilized to study the effect of geometrically nonlinear elasto-plastic design. The plastic behavior can be controlled by defining a limit on the plastic limit load multipliers. The suggested work's efficiency is demonstrated via a 2D benchmark problem. In case of elastic material, a 2D model of U-shape plate is used for probabilistic design of linear and geometrically nonlinear topology optimizations. Furthermore, a 2D elasto-plastic model is considered for reliability-based design to demonstrate that the suggested approach can determine the best topological solution.


Offspring of parents with recurrent depression: which features of parent depression index risk for offspring psychopathology?
Parental depression is associated with an increased risk of psychiatric disorder in offspring, although outcomes vary. At present relatively little is known about how differences in episode timing, severity, and course of recurrent depression relate to risk in children. The aim of this study was to consider the offspring of parents with recurrent depression and examine whether a recent episode of parental depression indexes risk for offspring psychopathology over and above these other parental depression features. Three hundred and thirty seven recurrently depressed parents and their offspring (aged 9-17) were interviewed as part of an ongoing study, the 'Early Prediction of Adolescent Depression Study'. The Child and Adolescent Psychiatric Assessment was used to assess two child outcomes; presence of a DSM-IV psychiatric disorder and number of DSM-IV child-rated depression symptoms. Children whose parents had experienced a recent episode of depression reported significantly more depression symptoms, and odds of child psychiatric disorder were doubled relative to children whose parents had not experienced a recent episode of depression. Past severity of parental depression was also significantly associated with child depression symptoms. Statistical analyses preclude causal conclusions pertaining to parental depression influences on offspring psychopathology; several features of parental depression were recalled retrospectively. This study suggests that particular features of parental depression, specifically past depression severity and presence of a recent episode, may be important indicators of risk for child psychiatric disorder and depressive symptoms.


Hepatic deiodinase activity is dispensable for the maintenance of normal circulating thyroid hormone levels in mice.
Thyroid hormone (TH) homeostasis depends on peripheral activation and inactivation of iodothyronines by selenoenzymes of the deiodinase (Dio) family. We genetically inactivated hepatic selenoenzyme expression, including Dio1, in order to determine the contribution of hepatic Dio to circulating TH levels. Serum levels of TSH, total T(4), and total T(3) were not different from controls. We measured Dio1 and Dio2 in kidney, skeletal muscle, heart, brown adipose tissue, and brain, but did not find compensatory up-regulation in these tissues. Finally, we determined expression in the liver of the following T(3) target genes: Spot14, alpha-glycerophosphate dehydrogenase (alphaGPD), and malic enzyme (ME). On the transcript level, both Spot14 and alphaGPD were reduced in Dio-deficient liver to about 60-70% of controls. However, mRNA and activity of ME were significantly increased in the same mice. Together, our results indicate that hepatic Dio1 activity is not absolutely required to sustain the euthyroid state in mice.


Isolation and structure determination of a new sesquiterpene lactone from Nauplius aquaticus.
The aerial part of Nauplius aquaticus afforded a new sesquiterpene lactone with a humulanolide skeleton, 6,7,9,10-tetrahydroasteriscunolide (1), in addition to the known asteriscunolides A (2) and D (3). Their structures were established principally by two-dimensional NMR spectroscopy.


Peptidase activities in human semen.
Enkephalins are one of the opioids present in human semen and to date their function in this tissue remains unknown. The present work studies enkephalin-degrading enzyme activities, puromycin-sensitive alanyl aminopeptidase (AAP-S), puromycin-insensitive alanyl aminopeptidase N (Ap N) and neprilysin (NEP) in human seminal fractions. AAP-S activity was not detected in any fractions, whereas Ap N appeared in soluble and particulate sperm fractions in seminal fluid and in prostasome fraction. With regard to NEP activity, this was exclusively located in prostasome membranes. The high activity values observed in the prostasome fraction suggested that these peptidases and their substrates could be involved in seminal physiology.


Fetal stomach paracentesis in combined duodenal and esophageal atresia.
Fetuses with concomitant duodenal atresia (DA) and esophageal atresia (EA) might develop in utero gastric rupture as well as neonatal respiratory complication due to dilated stomach and duodenum. Our patient with the typical "double bubble" appearance was highly suspected to have DA in the second trimester. Follow-up examinations revealed a massively dilated stomach and duodenum with a dilated distal esophagus, indicating concomitant DA and EA. With advancing pregnancy, the fetal abdomen progressively increased in size by retention of fluid in the closed loop of DA and EA. To avoid gastric perforation, prenatal stomach paracentesis using an ultrasound-guided needle was performed three times until delivery. A male neonate born at 37 weeks gestation showed no respiratory complication. Perinatal clinical features and operative findings revealed combined DA and EA (gross type A). He was successfully managed with duodenoduodenostomy, followed by esophago-esophagostomy. On fetal sonography, the marked "double bubble" appearance and the cystic structure presenting peristalsis-like movement above the diaphragm were indicative of concomitant DA and EA. Fetal stomach paracentesis could contribute to the improvement of perinatal outcomes in fetuses with this pathological condition.


Thermo-responsive non-woven scaffolds for "smart" 3D cell culture.
The thermo-responsive polymer poly(N-isopropylacrylamide) has received widespread attention for its in vitro application in the non-invasive, non-destructive release of adherent cells on two dimensional surfaces. In this study, 3D non-woven scaffolds fabricated from poly(propylene) (PP), poly(ethylene terephthalate) (PET), and nylon that had been grafted with PNIPAAm were tested for their ability to support the proliferation and subsequent thermal release of HC04 and HepG2 hepatocytes. Hepatocyte viability and proliferation were estimated using the Alamar Blue assay and Hoechst 33258 total DNA quantification. The assays revealed that the pure and grafted non-woven scaffolds maintained the hepatocytes within the matrix and promoted 3D proliferation comparable to that of the commercially available Algimatrix™ alginate scaffold. Albumin production and selected cytochrome P450 genes expression was found to be superior in cells growing on pure and grafted non-woven PP scaffolds as compared to cells grown as a 2D monolayer. Two scaffolds, namely, PP-g-PNIPAAm-A and PP-g-PNIPAAm-B were identified as having far superior thermal release capabilities; releasing the majority of the cells from the matrices within 2 h. This is the first report for the development of 3D non-woven, thermo-responsive scaffolds able to release cells from the matrix without the use of any enzymatic assistance or scaffold degradation.


Right hepatectomy in patients over 70 years of age: an analysis of liver function and outcome.
As a consequence of the increase in life expectancy, hepatobiliary surgeons have to deal with an emerging aged population. We aimed to analyze the liver function and outcome after right hepatectomy (RH) in patients over 70 years of age. From January 2006 to December 2009, we prospectively collected data of 207 consecutive elective hepatectomies. In patients who had RH, cardiac risk was assessed by a dedicated preoperative workup. Liver failure (LF) was defined by the "fifty-fifty" criteria at postoperative day 5 (POD) and morbidity by the Clavien-Dindo classification. Liver function tests (LFTs) and short-term outcome were retrospectively analyzed in patients over (elderly group, EG) and younger (young group, YG) than 70 years of age. Eighty-seven consecutive RH were performed during the study period. Indication for surgery included 90 % malignancy in 47 % of patients requiring preoperative chemotherapy. ASA grade > 2 (44 vs. 16 %, p = 0.027), ischemic heart disease (17 vs. 5 %, p = 0.076), and preoperative cardiac failure (26 vs. 2 %, p < 0.001) were more frequent in the EG (n = 23) than in the YG (n = 64). Both groups were similar regarding rates of normal liver parenchyma, chemotherapy and intraoperative parameters. The overall morbidity rates were comparable, but the serious complication (grades III-V) rate was relatively higher in the EG (39 vs. 25 %, p = 0.199), particularly in patients with diabetes mellitus (100 vs. 29 %, p = 0.04) and those who had additional nonhepatic surgery (67 vs. 35 %, p = 0.110) and transfusions (44 vs. 30 %, p = 0.523). The 90-day mortality rate was similar (9 % in the EG vs. 3 % in the YG, p = 0.28) and was related to heart failure in the EG. LFTs showed a similar trend from POD 1 to 8, and patients ≥70 years of age had no liver failure. Age ≥70 years alone is not a contraindication to RH. However, major morbidity is particularly higher in the elderly with diabetes. This high-risk group should be closely monitored in the postoperative course. Liver function is not altered in the elderly patient after RH.


Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies.
The use of assisted reproductive technologies (ARTs) is steadily increasing worldwide. The outcomes associated with treatment for an individual's long-term health, including risk of cardiovascular disease (CVD), remain largely unknown, due to the small number of studies and their limited follow-up time. To study whether the risk of CVD is increased among individuals who have given birth after ART compared with those who have given birth without ART. A registry-based cohort study was conducted using nationwide data from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1985-2015). Data analysis was conducted from January to August 2022. A total of 2 496 441 individuals with a registered delivery in the national birth registries during the study period were included, and 97 474 (4%) of these gave birth after ART. Data on ART conception were available from ART quality registries and/or medical birth registries. Information on CVD was available from patient and cause of death registries. The risk of CVD was estimated with Cox proportional hazards regression, adjusting for age, calendar year of start of follow-up, parity, diagnosis of polycystic ovary syndrome, diabetes, chronic hypertension, and country. Median follow-up was 11 (IQR, 5-18) years. The mean (SD) age of women with no use of ART was 29.1 (4.9) years, and the age of those who used ART was 33.8 (4.7) years. The rate of any CVD was 153 per 100 000 person-years. Individuals who gave birth after using ART had no increased risk of CVD (adjusted hazard ratio [AHR], 0.97; 95% CI, 0.91-1.02), with evidence of heterogeneity between the countries (I2 = 76%; P = .01 for heterogeneity). No significant differences in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis were noted with use of ART. However, there was a tendency for a modest reduction in the risk of myocardial infarction (AHR, 0.80; 95% CI, 0.65-0.99), with no notable heterogeneity between countries. The findings of this study suggest that women who gave birth after ART were not at increased risk of CVD over a median follow-up of 11 years compared with those who conceived without ART. Longer-term studies are needed to further examine whether ART is associated with higher risk of CVD.


Minocycline inhibits growth of epithelial ovarian cancer.
These studies were designed to determine whether minocycline inhibits ovarian cancer growth in vitro and in vivo and the molecular mechanisms involved. The effect of minocycline on ovarian cancer cell proliferation, cell cycle progression and apoptosis was assessed using human ovarian cancer cell lines OVCAR-3, SKOV-3 and A2780. Then, the capacity of minocycline to inhibit growth of OVCAR-3 xenografts in female nude mice was examined. Minocycline inhibited cell proliferation and colony formation, down-regulated cyclins A, B and E leading to arrest of cells in the G(0) phase of the cycle and suppression of DNA synthesis. Furthermore, exposure of these cells to minocycline led to DNA laddering, activation of caspase-3 and cleavage of PARP-1. In nude mice bearing sub-cutaneous tumors, minocycline suppressed tumor proliferation index, angiogenesis and tumor growth. These findings provide the initial basis for further evaluation of minocycline in the treatment of ovarian cancer.


Environmental harshness, heat stress, and Marmota flaviventris.
Yellow-bellied marmots (Marmota flaviventris) were studied at three sites in central Oregon. Juveniles substantially reduced their foraging activity when equivalent black-body temperatures exceeded their upper critical temperature. Inclusion of heat stress into estimates of environmental harshness drastically reduced the differences in available foraging time between high elevation and low elevation sites.


Identification and quantification of target metabolites combined with transcriptome of two rheum species focused on anthraquinone and flavonoids biosynthesis.
Rheum emodi is a perennial herb and an important medicinal plant, with anthraquinones and flavonoids as its main bioactive compounds. However, there is little knowledge about the biosynthetic pathway of anthraquinones in rhubarbs. In this study, we qualitatively and quantitatively assessed 62 pharmacological metabolites in rhubarb using dynamic multiple reaction monitoring (dMRM) of triple-quadrupole mass spectrometry (QqQ-MS), including 21 anthraquinones, 17 flavonoids, 6 stilbenes, 12 gallate esters, 3 tannins, and 3 others. Besides, the metabolomics results showed significant differences among all the 60 metabolites, except for gallic acid and piceatannol-O-β-glucoside. The combined transcriptome data of R. palmatum L. (RPL) and R. officinale Baill. (ROB) showed that 21,691 unigenes were annotated in the metabolic pathways. Taken together, 17 differentially expressed genes (DEGs) were associated with the anthraquinone biosynthetic pathway. Additionally, a significant correlation between anthraquinone peak intensity and DEG expression level existed, validating that DEGs contribute to the anthraquinone biosynthetic pathway. RT-qPCR results showed that the cluster-14354.38156 gene may catalyze the O-methylation of emodin to produce physcion. This study provides a useful resource for further studies on secondary metabolism in rhubarb and the combination analysis of transcriptome and metabolome, which can help with the discovery of enzyme genes involved in metabolite biosynthesis.


Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review.
Extracellular matrix (ECM) components confer biomechanical properties, maintain cell phenotype and mediate tissue homeostasis. ECM remodeling is complex and plays a key role in both physiological and pathological processes. Matrix metalloproteinases (MMPs) are a group of enzymes responsible for ECM degradation and have been accepted as a key regulator in ECM remodeling. In this mini-review, we summarize MMPs categories, functions and the targeted substrates. We then discuss current understanding of the role of MMPs-mediated events, including inflammation reaction, angiogenesis, cellular activities, etc., in ECM remodeling in the context of regenerative medicine.


Bifunctionalization of carbon nitride by incorporation of thiophene ring and polar nickel complex to promote photocatalytic activity for hydrogen evolution.
Photocatalytic performance of polymeric carbon nitride (CN) is primarily restricted by limited light utilization and poor charge separation efficiency. To this end, skeleton modification strategy was adopted by attaching thiophene ring and polar nickel complex (NiL) onto CN. The obtained bifunctionalized carbon nitride (TCN-NiL) displayed obviously elevated optical absorption and photoexcited charge separation efficiency. The NiL, with polar structure, plays as active sites like cocatalyst thus exhibited platinum-like H2 evolution activity from water splitting under visible light. The optimized photocatalytic H2 generation rate over TCN-NiL reached 136.7 μmol·h-1 without any cocatalyst, the highest rate reported so far in noble-metal-free CN-based catalysts, which is 5 times of that of CN loaded with 3 wt% Pt. Additionally, the maximum wavelength of performing H2 production capacity over TCN-NiL extends to 550 nm from 450 nm of CN, suggesting an excellent visible light absorption ability. This work provides a way for modifying CN to enhance the photocatalytic activities in a noble metal free system.


Nonexistence of conformally flat slices in Kerr and other stationary spacetimes.
It is proved that stationary solutions to the vacuum Einstein field equations with a nonvanishing angular momentum have no Cauchy slice that is maximal, conformally flat, and nonboosted. The proof is based on results coming from a certain type of asymptotic expansion near null and spatial infinity--which also show that the development of Bowen-York-type data cannot have a development admitting a smooth null infinity--and from the fact that stationary solutions do admit a smooth null infinity.


Superoxide generation from constitutive nitric oxide synthase in astrocytes in vitro regulates extracellular nitric oxide availability.
Oxygen-derived free radicals play an important role in the physiology and pathophysiology of brain cell function. Because of their labile nature, however, it has been difficult to investigate their actions directly. This problem has been addressed, in primary rat brain cell cultures, in this study by utilization of two novel electrochemical sensors. It has been demonstrated that extracellular superoxide originates from the astrocytic subpopulation in a calcium/calmodulin dependent manner and responds to constitutive nitric oxide synthase inhibition. The results indicate a novel function for the astrocytic constitutive nitric oxide synthase in regulating extracellular superoxide release and, therefore, controlling neuronal nitric oxide availability.


Friction in femoral prosthesis and photoelastic model cone taper joints.
Static axial push-on and lift-off, and push-on and twist-off experiments were designed and performed to measure the effective, room-temperature coefficient of friction mu for different design femoral prosthesis cone taper joints comprising a universal head on a stem spigot. Alumina and metal heads were tested on metal spigots using either distilled water, Ringer's solution, blood or no lubricant. Complementary push-on and lift-off friction tests of Araldite model joints for subsequent frozen-stress, photoelastic stress analysis were performed at 130 degrees C. It was found that lubricant caused little decrease in the values of the coefficient of friction in prosthesis tapers. The values measured were typically mu = 0.2 for an alumina head on a Co-Cr-Mo or Ti-6Al-4V spigot, mu = 0.15 for a Co-Cr-Mo head on a Co-Cr-Mo or Ti-6Al-4V spigot and mu = 0.13 for a stainless steel head on a stainless steel spigot. For Araldite photoelastic models of an alumina head on a Vitallium spigot, as-cast taper surfaces lubricated with silicone grease gave consistent friction of typically mu = 0.14. The axial displacement of model heads on their spigots were compared with predicted values and previously measured values for prosthesis heads.


Protein profiling of hemocytes from the terrestrial crustacean Armadillidium vulgare.
To establish and maintain a successful infection, microbial pathogens have evolved various strategies to infect the host in the face of a functional immune system. In this context, the alpha-proteobacteria Wolbachia capacities to infect new host species have been greatly evidenced. Indeed, in terrestrial isopods, experimentally transferred Wolbachia invade all host tissues, including immune cells such as hemocytes. To investigate mechanisms that have to be avoided by bacteria to maintain themselves in hemocytes, we characterized the hemocyte proteome of Armadillidium vulgare by a 2D gel electrophoresis approach. Fifty-six proteins were identified and classified into functional groups (stress and immunity, glucose metabolisms, cytoskeleton, others). We focused on immune response and cytoskeleton proteins often exploited by bacteria to invade their host. From the microsequences obtained by mass spectrometry, PCR primers were designed to amplify seven partial cDNAs encoding masquerade, alpha2-macroglobulin, transglutaminase, MnSOD, calreticulin, cyclophilin, and vinculin, confirming their expression in hemocytes.


Benzodiazepine analogues. Part 21. 13C NMR analysis of benzoxathiepine derivatives.
The influence of substituents and structure on the 13C NMR spectra of four series of benzoxathiepine derivatives has been investigated. Signal assignments in the 13C NMR spectra have been facilitated by the use of several predictive methods, permitting comparison of their relative efficacy.


Secondary cytoreductive surgery in epithelial ovarian cancer: nonresponders to first-line therapy.
Thirty-three patients with progressive or stable epithelial ovarian cancer who underwent secondary tumor-reductive surgery at the University of Texas M. D. Anderson Cancer Center were retrospectively studied. All patients had primary cytoreductive surgery followed by chemotherapy. Lack of response to chemotherapy was clinically documented preoperatively. The tumors of 55% of the patients were secondarily cytoreduced to a greatest diameter of less than 2 cm. Sixty-six percent of the patients required bowel resection. Operative morbidity occurred in 24% of patients, mostly in those with bowel resection. Overall, median survival after secondary surgery was 9.4 months. For patients with residual tumor less than 1 cm, median survival after secondary surgery was 19.5 months, compared with 8.3 months for patients with residual tumor of 1 cm or more (P less than 0.004). Patients with an interval between primary cytoreductive effort and secondary surgery of less than 12 months survived a median of 7.3 months, compared with an 18.3-month median survival for patients with an interval of 12 months or more (P less than 0.004). The present study provided no evidence that secondary surgery is of significant benefit in most patients who have progressive disease during chemotherapeutic treatment of epithelial ovarian cancer.